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Sample records for successful allogeneic bone

  1. Successful Treatment with Ganciclovir for Cytomegalovirus Duodenitis following Allogenic Bone Marrow Transplantation

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    Ahn, Jin Hee; Lee, Je-Hwan; Lee, Kyoo-Hyung; Kim, Woo-Kun; Lee, Jung-Shin; Bahng, Hyeseung; Jung, Hwoon-Yong; Kim, Yang-Soo; Kim, Onja; Kim, Sang-Hee

    1999-01-01

    Cytomegalovirus (CMV) disease is a major cause of morbidity and mortality in immunocompromised patients. CMV enteritis should be considered when nausea and vomiting continue 3 to 4 weeks after bone marrow transplantation (BMT). The treatment of CMV enteritis is not well established. We report a CMV duodenitis patient following allogenic bone marrow transplantation. The patient had prolonged nausea and vomiting for 5 weeks after bone marrow transplantation and CMV duodenitis was diagnosed by the gastroduodenoscopic mucosal biopsy which showed cytomegalic cells. Ganciclovir treatment for 3 weeks resulted in the resolution of symptoms and promoted healing of the lesion. The patient was free of CMV infection until 288 days after allogenic BMT without maintenance ganciclovir treatment. PMID:10063321

  2. Progressive Langerhans cell histiocytosis in an infant with Klinefelter syndrome successfully treated with allogeneic bone marrow transplantation.

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    Frost, J D; Wiersma, S R

    1996-11-01

    We describe successful treatment of an infant with progressive Langerhans cell histiocytosis (LCH) with allogeneic bone marrow transplantation (BMT), and discuss a chromosomal abnormality discovered in his LCH-affected tissue. A 4-month-old male infant with a seborrheic-appearing rash, respiratory collapse, and spontaneous pneumothorax is presented. LCH was diagnosed with primary involvement of skin and lungs. His disease progressed despite aggressive multiagent chemotherapy that included high-dose methylprednisolone, vinblastine, cyclophosphamide, methotrexate, 2-chlorodeoxyadenosine, and etoposide. The patient was successfully treated with myeloblative therapy and low-dose total body irradiation followed by allogeneic BMT at the age of 16 months, at which time he had multisystem involvement. One hundred percent 47XXY/14p+ cells were identified from a lung biopsy; peripheral blood chromosomal analysis demonstrated mosaic 47XXY/14p+, and normal 46XY. Allogeneic BMT may be used successfully in the treatment of refractory, progressive LCH in infants, who are at highest risk of mortality. The cytogenetic association between Klinefelter syndrome and LCH has not been described previously. Cytogenetic analysis of other patients with LCH may be beneficial in determining a genetic association between LCH and Klinefelter syndrome and/or abnormalities of chromosome 14.

  3. Allogenic bone grafts in post-traumatic juxta-articular defects: Need for allogenic bone banking.

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    Mishra, Anil Kumar; Vikas, Rohit; Agrawal, H S

    2017-07-01

    Allogenic bone banking provide both structural and granular bone grafts for various orthopaedic, spinal, oncological and dental surgeries. However allogenic bones, presently, are not readily available. This article discusses the clinical applications of the allogenic grafts, the screening criteria and procedure for maintenance of such a bone banking facility. This article demonstrates the effective role of allogenic bone in a case of post-traumatic bone loss situation and discusses the growing need and present situation of bone banking in our country.

  4. Successful repigmentation of vitiligo after allogeneic bone marrow transplantation for Hodgkin′s lymphoma by autologous noncultured melanocyte-keratinocyte transplantation

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    Huijuan Tang

    2015-01-01

    Full Text Available The treatment of vitiligo is derisory since the pathogenesis of vitiligo is not clear at present. Most conservative treatments are difficult to approach satisfactory therapy. So transplantation is the only way left when the disease becomes insensitive to those conservative treatments. Here we describe an 18-year-old patient who developed vitiligo, which was triggered by graft-versus-host disease after a allogeneic bone marrow transplantation for the treatment of Hodgkin′s lymphoma from his sister. In the following treatment to vitiligo, the patient successfully performed the transplantation of autologous uncultured melanocyte on the premise of poor reaction to other conservative methods. We infer that transplantation can be a treatment of the vitiligo after allogeneic bone marrow transplantation.

  5. Successful management of EBV-PTLD in allogeneic bone marrow transplant recipient by virological-immunological monitoring of EBV infection, prompt diagnosis and early treatment.

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    Chiereghin, Angela; Bertuzzi, Clara; Piccirilli, Giulia; Gabrielli, Liliana; Squarzoni, Diego; Turello, Gabriele; Ferioli, Martina; Sessa, Mariarosaria; Bonifazi, Francesca; Zanoni, Lucia; Sabattini, Elena; Lazzarotto, Tiziana

    2016-02-01

    Epstein-Barr virus-related post-transplant lymphoproliferative disorder (EBV-PTLD) is an uncommon, but frequently fatal, complication after allogeneic hematopoietic stem cell transplant. Prospective post-transplant virological and immunological monitoring allowed to successfully manage a patient who developed both polymorphic and monomorphic, "diffuse large B-cell lymphoma like", as an EBV-PTLD, 65days after allogeneic bone marrow transplant. Early detection of significant increase in EBV DNA level in patient's peripheral blood (peak of viral load equal to 119,039copies/mL whole blood, +56day after transplant) led to administration of pre-emptive anti-CD20 monoclonal antibody (rituximab) and close clinical monitoring. After one week, physical exam revealed laterocervical adenopathy. Histopathologic features, immunohistochemical characterization and in situ hybridization study allowed to establish a diagnosis of EBV-related PTLD. Immunological monitoring showed no EBV-specific T-cell responses during EBV replication, thus potentially explaining the occurrence of high EBV load with subsequent PTLD development. A total of four doses of anti-CD20 monoclonal antibody were administered and at the end of the treatment, EBV infection was cleared and imaging technique showed complete disease remission. In conclusion, the early use of anti-CD20 monoclonal antibody proved to be a safe and effective treatment strategy for EBV-PTLD. Moreover, combined virological-immunological monitoring of EBV infection may more accurately assess patients at higher risk for EBV-PTLD. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Variant Purification of an Allogeneic Bone Block

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    Lorenz, Jonas; Schlee, Markus; Al-Maawi, Sarah; Chia, Poju; Sader, Robert A.

    2017-01-01

    Objective This short communication reports on a histological analysis of the composition of the commercially available Maxgraft® allogeneic bone block. Materials and Methods Based on previously published, easily applicable histological methods, blanc samples of the Maxgraft® allogeneic bone block have been decalcified, dehydrated and embedded in paraffin before histological and histochemical staining. Afterwards, the slides were evaluated for their material characteristics, such as the bone matrix structure and other components, including collagen or cells/cell remnants. Results The results show that this bone block exhibits a trabecular structure with lamellar sub-organization. Additionally, cellular remnants within the osteocyte lacunae and at the outer trabecular surfaces reside together with remnants of the former inter-trabecular fatty and connective tissue, i.e., collagenous structures and connective tissue cells or cell remnants. Conclusion Consistent with a previous study on this topic, the data presented here demonstrate that some of the certified purification techniques might not allow for the production of allogeneic materials free of organic cell and tissue components. PMID:28827851

  7. Bone Grafts in Jaw Cysts- Hydroxyapatite & Allogenic Bone – A Comparative Study

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    Showkat Mamun

    2009-11-01

    Full Text Available Background: Auto bone is the gold standard in bone grafting. However, the morbidity and additional surgical time associated with its collection, as well as the limited supply, have stimulated the search for substitutes. Allograft is more limited than autograft because it yields more variable clinical results. Composite synthetic grafts offer an alternative because Hydroxyapatite is chemically identical to the inorganic matrix of living bones and it can be processed synthetically. The intent was to evaluate these two graft materials for clinical use and to provide an insight on the different grafting strategies to enhance bone formation. Objective: To find out the bone healing process and the prognostic value for the patient using hydroxyapatite alloplastic material and allogenic bone graft. Method: Total 28 patients were included in the study after the clinical and radiological evaluation where 14 cases were treated with allogenic-bone graft and rest 14 cases were treated with hydroxyapatite alloplastic material after enucleation of the cystic lesion in random manner. The integration of hydroxyapatite and allogenic bone was assessed with postoperative lesion diameter, trabecular pattern, histopathological and scintigraphic examination of the successful graft cases. Statistical analysis was carried out by ‘unpaired T test' and ‘Chi square' test. Result: The radiological, histopathological and scintigraphical outcome of the patients treated with hydroxyaptite granule bone graft were clinically and statistically superior in comparison with those who were treated with allogenic bone graft. Conclusion: This safe and osteoconductive hydroxyapatite appears suitable for filling bone defects and bone cavities, showing less resorption and a rapid osseous integration. Key words: Hydroxyapatite; allogenic bone; scintigraphy; radiology; histopathology.DOI: 10.3329/bsmmuj.v2i1.3707 BSMMU J 2009; 2(1: 25-30

  8. Alpha-1-antitrypsin monotherapy reduces graft-versus-host disease after experimental allogeneic bone marrow transplantation

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    Tawara, I.; Sun, Y.; Lewis, E.C.; Toubai, T.; Evers, R.; Nieves, E.; Azam, T.; Dinarello, C.A.; Reddy, P.

    2012-01-01

    Acute graft-versus-host disease (GvHD) is a major complication that prevents successful outcomes after allogeneic bone marrow transplantation (BMT), an effective therapy for hematological malignancies. Several studies demonstrate that donor T cells and host antigen-presenting cells along with

  9. Successful treatment of natural killer (NK) cell leukemia following a long-standing chronic active Epstein-Barr virus (CAEBV) infection with allogeneic bone marrow transplantation.

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    Ebihara, Y; Manabe, A; Tanaka, R; Yoshimasu, T; Ishikawa, K; Iseki, T; Hayakawa, J; Maeda, M; Asano, S; Tsuji, K

    2003-06-01

    The optimal treatment for natural killer (NK) cell leukemia after chronic active Epstein-Barr virus (CAEBV) infection has not been determined. A 15-year-old boy presented with NK cell leukemia following CAEBV infection for 5 years. The peripheral blood and BM had an increased number of CD3(-)CD56(+) large granular lymphocytes and a monoclonal integration of the EBV genome was detected. Chemotherapy was not sufficiently effective to control the disease. Allogeneic BMT from an HLA-identical sister was performed using a conditioning regimen consisting of total body irradiation, cyclophosphamide and thiotepa. The patient is disease-free with a perfect performance status 24 months after BMT. This is the first report to show that allogeneic BMT is potentially able to cure NK cell leukemia after CAEBV infection.

  10. Chronic active Epstein-Barr virus infection with mosquito allergy successfully treated with reduced-intensity unrelated allogeneic bone marrow transplantation in a boy.

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    Matsunaga, Takayuki; Kurosawa, Hidemitsu; Okuya, Mayuko; Nakajima, Daisuke; Hagisawa, Susumu; Sato, Yuya; Fukushima, Keitaro; Sugita, Kenichi; Arisaka, Osamu

    2009-03-01

    EBV-infected T-/NK cells play an important role in the pathogenesis of mosquito allergy, and the prognosis of most patients with mosquito allergy is poor without proper treatment. We describe a 13-yr-old boy who had CAEBV with mosquito allergy and was successfully treated with BMT from an unrelated donor after reduced-intensity preconditioning. Because combination chemotherapy failed to achieve CR, we performed unrelated BMT to reconstitute normal immunity and eradicate any residual EBV-infected cells. To reduce complications after BMT, we selected a reduced-intensity preconditioning regimen consisting of fludarabine, l-phenylalanine mustard, and antithymocyte Ig instead of a conventional myeloablative preconditioning. Although grade II acute GVHD developed, it was successfully controlled with immunosuppressive therapy. After 27 months, the patient has been well without any signs of CAEBV, and the EBV DNA has been undetectable with real-time PCR analysis. We conclude that RIST from the bone marrow of an unrelated donor is indicated for some patients who have CAEBV that is refractory to chemotherapy and who have no HLA-matched related donors or cord blood as a source of stem cells.

  11. Use of allogeneic bone graft in maxillary reconstruction for installation of dental implants.

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    Gomes, Kelston Ulbricht; Carlini, João Luiz; Biron, Cássia; Rapoport, Abrão; Dedivitis, Rogério A

    2008-11-01

    The aim of this study is to evaluate the efficacy of the application of allogenous bone at the maxillomandibular reconstructions for future rehabilitation with dental implants. The patients were submitted to reconstruction of maxilla, using allogeneic bone grafts, in 3 different techniques: onlay grafts for lateral ridge augmentation, onlay and particulate bone for sinus lift grafting, and particulate alone for sinus lift grafts. Clinical and radiographic control was done at the postoperative phase for at least 8 months, until the patient could be submitted to the installation of dental implants. The results showed success in the majority of the cases, and dental implants could be installed. This can be considered an excellent alternative when compared with the use of autogenous grafts; because handling is easier, there is a great amount of material available and a possibility of using local anesthesia, and consequently there is a reduction of patient morbidity.

  12. Sinusitis in patients undergoing allogeneic bone marrow transplantation - a review.

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    Drozd-Sokolowska, Joanna Ewa; Sokolowski, Jacek; Wiktor-Jedrzejczak, Wieslaw; Niemczyk, Kazimierz

    Sinusitis is a common morbidity in general population, however little is known about its occurrence in severely immunocompromised patients undergoing allogeneic hematopoietic stem cell transplantation. The aim of the study was to analyze the literature concerning sinusitis in patients undergoing allogeneic bone marrow transplantation. An electronic database search was performed with the objective of identifying all original trials examining sinusitis in allogeneic hematopoietic stem cell transplant recipients. The search was limited to English-language publications. Twenty five studies, published between 1985 and 2015 were identified, none of them being a randomized clinical trial. They reported on 31-955 patients, discussing different issues i.e. value of pretransplant sinonasal evaluation and its impact on post-transplant morbidity and mortality, treatment, risk factors analysis. Results from analyzed studies yielded inconsistent results. Nevertheless, some recommendations for good practice could be made. First, it seems advisable to screen all patients undergoing allogeneic hematopoietic stem cell transplantation with Computed Tomography (CT) prior to procedure. Second, patients with symptoms of sinusitis should be treated before hematopoietic stem cell transplantation (HSCT), preferably with conservative medical approach. Third, patients who have undergone hematopoietic stem cell transplantation should be monitored closely for sinusitis, especially in the early period after transplantation. Copyright © 2016 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  13. Transplantation of allogenic chondrocytes with chitosan hydrogel-demineralized bone matrix hybrid scaffold to repair rabbit cartilage injury.

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    Man, Zhentao; Hu, Xiaoqing; Liu, Zhenlong; Huang, Hongjie; Meng, Qingyang; Zhang, Xin; Dai, Linghui; Zhang, Jiying; Fu, Xin; Duan, Xiaoning; Zhou, Chunyan; Ao, Yingfang

    2016-11-01

    Cartilage tissue engineering is the hotspot of cartilage repair. The allogenic chondrocytes appear to be a promising source of seed cells in cartilage tissue engineering. In this study, we aimed to transplant allogenic chondrocytes with chitosan hydrogel (CS)-demineralized bone matrix (DBM) hybrid scaffold (CS/DBM) to repair rabbit cartilage injury with one-step operation. After the CS/DBM scaffold was successfully fabricated, it showed that the porous CS filled the large pores of DBM, which improved the distribution of seed cells in the CS/DBM scaffold. The allogenic chondrocytes at second passage were transplanted with different scaffolds to repair rabbit cartilage injury. Twenty-four weeks after surgery, the cartilage defect in the CS/DBM group was successfully filled as shown by MRI. Moreover, the histological score of CS/DBM group was significantly higher than that of the other groups. On the aspect of biomechanical property, the regenerated cartilage in the CS/DBM group were superior to those in the other groups as determined by nanoindentation. Meanwhile, no obvious inflammatory response was observed after the transplantation of allogenic chondrocytes at 24 weeks post-surgery. Furtherly, gene expression profile for cells within the repair tissue was compared with the allogenic chondrocytes before transplantation using Agilent microarray and RT-qPCR. The results showed that some genes beneficial to cartilage regeneration, such as BMP-7, HGF, and IGF-1, were upregulated one month after transplantation. Consequently, our study demonstrated that the transplantation of allogenic chondrocytes with CS/DBM scaffold successfully repaired rabbit cartilage injury with only one-step operation, thereby providing new insights into cartilage tissue engineering. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Iron carrier proteins facilitate engraftment of allogeneic bone marrow and enduring hemopoietic chimerism in the lethally irradiated host

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    Pierpaoli, W.; Dall' Ara, A.; Yi, C.X.; Neri, P.; Santucci, A.; Choay, J. (Institute for Biomedical Research, Quartino (Switzerland))

    1991-04-15

    Cell-free supernatants of rabbit bone marrow were fractionated, separated, and purified by Ultrogel and Superose chromatography. A single fraction promoted engraftment of allogeneic bone marrow and enduring hemopoietic chimerism across the H-2 barrier in lethally irradiated mice. This 'bio-active' fraction, analyzed by reducing SDS-PAGE electrophoresis, and transblotted on PVDF membrane, and purified by reverse-phase HPLC and SDS-PAGE electrophoresis yielded a main prealbumin band that when examined for primary structure by Edman degradation, proved to be rabbit transferrin. This was also attested by highly specific precipitation of the prealbumin band with polyclonal antibodies to rabbit transferrin. Iron-saturated human transferrin, lactotransferrin, and egg transferrin (conalbumin) were assayed in irradiated C57BL/6 mice infused with bone marrow from histoincompatible BALB/c donors. Mice treated with iron-loaded transferrins survive and develop enduring allogeneic chimerism with no discernible signs of graft-versus-host disease. Iron carrier proteins thus provide an unique means of achieving successful engraftment of allogeneic bone marrow in immunologically hostile murine H-2 combinations.

  15. Guillain–Barré syndrome after allogeneic bone marrow transplantation: Case report and literature review

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    Tomoko Yoshida, MD

    2016-09-01

    Full Text Available A 50-year-old man with acute myelogenous leukemia underwent allogeneic bone-marrow transplantation (BMT. He presented with severe diarrhoea 86 days post BMT and was diagnosed with graft-versus-host disease (GVHD based on skin and rectal biopsies. He complained of numbness and weakness in the distal extremities at 114 days after BMT. His symptoms rapidly deteriorated and he required mechanical ventilation for respiratory failure. His clinical course and the findings of a nerve conduction study fulfilled the criteria for diagnosis of Guillain–Barré syndrome (GBS. Sural nerve biopsy revealed active demyelination and infiltration of macrophages and CD8+ T-cells. After three cycles of intravenous immunoglobulin therapy, his symptoms gradually improved, and he could eventually walk unassisted. Although GBS has been known to develop after allogeneic BMT, the pathogenesis remains unclear, and specific treatment regimens have not been well established. Here, we report a case of GBS, caused by an immune-mediated mechanism related to GVHD, which was successfully treated using intravenous immunoglobulin therapy.

  16. Lung function after allogeneic bone marrow transplantation for leukaemia or lymphoma

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    Nysom, K; Holm, K; Hesse, B

    1996-01-01

    Longitudinal data were analysed on the lung function of 25 of 29 survivors of childhood leukaemia or lymphoma, who had been conditioned with cyclophosphamide and total body irradiation before allogeneic bone marrow transplantation, to test whether children are particularly vulnerable to pulmonary...... damage after transplantation. None developed chronic graft-versus-host disease. Transfer factor and lung volumes were reduced immediately after bone marrow transplantation, but increased during the following years. However, at the last follow up, 4-13 years (median 8) after transplantation, patients had...... to their age at bone marrow transplantation. In conclusion, patients had subclinical restrictive pulmonary disease at a median of eight years after total body irradiation and allogeneic bone marrow transplantation....

  17. Bone engineering-vitalisation of alloplastic and allogenic bone grafts by human osteoblast-like cells.

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    Hinze, Marc Christian; Wiedmann-Al-Ahmad, Margit; Glaum, Ricarda; Gutwald, Ralf; Schmelzeisen, Rainer; Sauerbier, Sebastian

    2010-07-01

    Human osteoblasts on non-sintered hydroxyapatite and demineralised bone matrix (DBX) were analysed in vitro to find out whether they would be suitable for reconstruction of bones in oral surgery. Human osteoblasts were isolated from the jaw during routine dental operations and seeded onto the two biomaterials. Cells were characterised by assay of alkaline phosphatase, detection of type 1 collagen, and production of osteocalcin. After 21 days of cultivation, the cell/biomaterial constructs were examined by scanning electron microscopy, thin sections, and propidium iodide/fluorescein diacetate staining. The osteoblasts formed a vital multiple cell layer on DBX within 3 weeks of cultivation. On hydroxyapatite, the cells showed no tendency to proliferate or migrate onto the synthetic biomaterial, or to form well-spread and viable cell constructs. These findings suggest that surface morphology or the presence of osteoinductive factors may have an important role in the adhesion and proliferation of osteoblasts. Human DBX can be colonised by human osteoblast-like cells in vitro, indicating the potential of allogeneic carriers for future procedures in bone engineering. Copyright 2009 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  18. On the Feasibility of Utilizing Allogeneic Bone Blocks for Atrophic Maxillary Augmentation

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    Alberto Monje

    2014-01-01

    Full Text Available Purpose. This systematic review was aimed at assessing the feasibility by means of survival rate, histologic analysis, and causes of failure of allogeneic block grafts for augmenting the atrophic maxilla. Material and Methods. A literature search was conducted by one reviewer in several databases. Articles were included in this systematic review if they were human clinical trials in which outcomes of allogeneic bone block grafts were studied by means of survival rate. In addition other factors were extracted in order to assess their influence upon graft failure. Results. Fifteen articles fulfilled the inclusion criteria and subsequently were analyzed in this systematic review. A total of 361 block grafts could be followed 4 to 9 months after the surgery, of which 9 (2.4% failed within 1 month to 2 months after the surgery. Additionally, a weighed mean 4.79 mm (95% CI: 4.51–5.08 horizontal bone gain was computed from 119 grafted sites in 5 studies. Regarding implant cumulative survival rate, the weighed mean was 96.9% (95% CI: 92.8–98.7%, computed from 228 implants over a mean follow-up period of 23.9 months. Histologic analysis showed that allogeneic block grafts behave differently in the early stages of healing when compared to autogenous block grafts. Conclusion. Atrophied maxillary reconstruction with allogeneic bone block grafts represents a reliable option as shown by low block graft failure rate, minimal resorption, and high implant survival rate.

  19. Clinical use of allogeneic bone granulates to reconstruct maxillary and mandibular alveolar processes.

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    Krasny, K; Kamiński, A; Krasny, M; Zadurska, M; Piekarczyk, P; Fiedor, P

    2011-10-01

    Lack of adequate mass of a patient's own bone is still a clinical problem in dental implantology; it precludes dental embedment. Surgical widening of an atrophied alveolar process with the use of an allogeneic bone granulate to fill the bone defect constitutes a first-line method to prepare for implant-prosthetic treatment. Transplantation of allogeneic material allows reconstruction of optimal height, thickness, and width of the alveolar process facilitating a procedure with a good long-term outcome. The study assessed outcomes following augmentation of atrophied alveolar processes before intraosseous implantation. Filling bone defects in the maxilla and mandible as an introductory measure for implant-prosthetic treatment was performed in 59 patients (24 females and 35 males of age range 22-65 years). Bone granulate was used for maxillary sinus floor elevation (n=29), augmentation of the postextraction alveoli (n=12), and filling of defects in the outer table of the compact bone formed following inflammatory conditions (n=18). The bone grafts were covered with plasma-rich fibrin (PRF) obtained from the patient's blood to accelerate the formation of synostoses and prevent epithelial penetration between the patients' own bone and the bone graft. In all of the patients normal union was observed, as confirmed by radiological images as well as intraprocedural assessment. Sufficient height and width as well as thickness of the alveolar process was obtained, which allowed embedment. Allogeneic bone granulate constitutes a good material to reconstruct maxillary and mandibular alveolar processes in out-patient care. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Lung function after allogeneic bone marrow transplantation for leukaemia or lymphoma

    DEFF Research Database (Denmark)

    Nysom, K; Holm, K; Hesse, B

    1996-01-01

    Longitudinal data were analysed on the lung function of 25 of 29 survivors of childhood leukaemia or lymphoma, who had been conditioned with cyclophosphamide and total body irradiation before allogeneic bone marrow transplantation, to test whether children are particularly vulnerable to pulmonary...... significantly reduced transfer factor, total lung capacity, and forced vital capacity (-1.0, -1.2, and -0.8 SD score, respectively), and increased ratio of forced expiratory volume in one second to forced vital capacity (+0.9 SD score). None of the patients had pulmonary symptoms, and changes were unrelated...... to their age at bone marrow transplantation. In conclusion, patients had subclinical restrictive pulmonary disease at a median of eight years after total body irradiation and allogeneic bone marrow transplantation....

  1. Horizontal and vertical maxillary osteotomy stability, in cleft lip and palate patients, using allogeneic bone graft

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    Kelston Ulbricht Gomes

    2013-10-01

    Full Text Available OBJECTIVE: This study was carried out to evaluate maxillary stability after orthodontic-surgical treatment of patients with cleft lip and palate. Cephalometric analysis was applied to two different groups, with and without allogeneic bone graft. METHODS: The sample comprised 48 patients with cleft lip and palate. The test group comprised 25 patients who, after correction of maxillary position, received allogeneic bone graft at the gap created by Le Fort I osteotomy. The control group comprised 23 patients and its surgical procedures were similar to those applied to the test group, except for the use of bone graft. Manual cephalometric analysis and comparison between lateral teleradiographs, obtained at the preoperative phase, immediate postoperative phase and after a minimum period of six months, were carried out. RESULTS: An higher horizontal relapse was observed in the control group (p0.05. CONCLUSION: The use of allogeneic bone graft in cleft lip and palate patients submitted to Le Fort I osteotomy contributed to increase postoperative stability when compared to surgeries without bone graft.

  2. Eradication of tumour cells by successive injections of allogeneic immune and hyperimmune peritoneal cells in a murine lymphoma system

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    Dullens, H.F.J.; Woutersen, R.A.; Weger, R.A. de; Otter, W. den

    2006-01-01

    Allogeneic C57BL immune and hyperimmune (vs SL2) peritoneal cells are used for eradication of DBA/2 derived SL2 lymphoma cells injected into the peritoneal cavity of DBA/2 mice. SL2 bearing DBA/2 mice are treated with 3, 5, or 8 successive i.p. injections of 2 × 106 allogeneic C57BL immune or

  3. Sinusitis in patients undergoing allogeneic bone marrow transplantation – a review

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    Joanna Ewa Drozd-Sokolowska

    Full Text Available Abstract Introduction Sinusitis is a common morbidity in general population, however little is known about its occurrence in severely immunocompromised patients undergoing allogeneic hematopoietic stem cell transplantation. Objective The aim of the study was to analyze the literature concerning sinusitis in patients undergoing allogeneic bone marrow transplantation. Methods An electronic database search was performed with the objective of identifying all original trials examining sinusitis in allogeneic hematopoietic stem cell transplant recipients. The search was limited to English-language publications. Results Twenty five studies, published between 1985 and 2015 were identified, none of them being a randomized clinical trial. They reported on 31–955 patients, discussing different issues i.e. value of pretransplant sinonasal evaluation and its impact on post-transplant morbidity and mortality, treatment, risk factors analysis. Conclusion Results from analyzed studies yielded inconsistent results. Nevertheless, some recommendations for good practice could be made. First, it seems advisable to screen all patients undergoing allogeneic hematopoietic stem cell transplantation with Computed Tomography (CT prior to procedure. Second, patients with symptoms of sinusitis should be treated before hematopoietic stem cell transplantation (HSCT, preferably with conservative medical approach. Third, patients who have undergone hematopoietic stem cell transplantation should be monitored closely for sinusitis, especially in the early period after transplantation.

  4. [Repair of rotator cuff tear by allogenic cortical bone anchor with suture bridge].

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    Wang, Ming-xin; Liu, Yu-jie; He, Wei; Li, Hai-feng; An, Bai-jing

    2012-07-03

    To evaluate the repair of rotator cuff tear by allogenic cortical bone anchors with the technique of suture bridge. A total of 18 patients with rotator cuff tear were recruited during the period of June 2006 to June 2009. There were 7 males and 11 females with an average age of 45.2 years old (range: 34 - 65). The locations included left shoulder (n = 11) and right shoulder (n = 7). Rotator cuff tear was repaired by allogenic cortical bone anchors with the technique of suture bridge under arthroscopy. The efficacy was evaluated by University of California Los Angeles (UCLA) standard score. The average follow-up period was 17.6 months (range: 12 - 36). The excellent rate of treatment was 100%. All rotator cuff tears were healed. Only 2 cases had minor pain and there was no limitation of joint activity. The bone anchor fully integrated with the subject area at Month 3 post-operation. The advantages of repairing rotator cuff tear by allograft cortical bone anchors with the technique of suture bridge includes minimal trauma, a large tendon bone area, firm fixation and a low cost. It is a better approach of repairing rotator cuff tear.

  5. Long-term outcomes of the use of allogeneic, radiation-sterilised bone blocks in reconstruction of the atrophied alveolar ridge in the maxilla and mandible.

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    Krasny, Marta; Krasny, Kornel; Fiedor, Piotr; Zadurska, Małgorzata; Kamiński, Artur

    2015-12-01

    Increasingly dental surgeons face the challenge of reconstruction of the height and/or thickness of the alveolar ridge as more and more patients wish to have permanent restoration of their dental defects based on intraosseous implants. Evaluation of human allogeneic bone tissue grafts in reconstruction of atrophied alveolar ridge as a pre-implantation procedure. The material comprised 21 patients aged 19-63, treated between 2009 and 2012 by the same surgeon. Restoration of bone tissue defects was performed with allogeneic, frozen, radiation-sterilised, corticocancellous blocks. The study included 26 grafting procedures with 7 procedures consisting in reconstruction of the alveolar ridge in the mandible and 19 in the maxilla. In all the cases the atrophied alveolar ridge was successfully reconstructed, which allowed placement of intraosseous implants in compliance with the initial treatment plan. After the treatment was completed the patients reported for follow-up annually. The average time of follow-up amounted to 39 months (28-50 months). None of the implants was lost during the follow-up period. There was one case of gingival recession causing aesthetics deterioration of the prosthetic restoration. In three cases the connector became unscrewed partially, which was corrected at the same visit. Frozen, radiation-sterilised, allogeneic bone blocks constitute good and durable bone-replacement material allowing effective and long-lasting reconstruction of the atrophied alveolar ridge to support durable, implant-based, prosthetic restoration.

  6. Application of human amniotic mesenchymal cells as an allogeneic transplantation cell source in bone regenerative therapy

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    Tsuno, Hiroaki [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Yoshida, Toshiko [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Nogami, Makiko [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Department of Orthopedic Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Koike, Chika; Okabe, Motonori [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Noto, Zenko [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Arai, Naoya; Noguchi, Makoto [Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Nikaido, Toshio, E-mail: tnikaido@med.u-toyama.ac.jp [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan)

    2012-12-01

    Autogenous mesenchymal stem cells (MSCs) have therapeutic applications in bone regenerative therapy due to their pluripotency. However, the ability of MSCs to proliferate and differentiate varies between donors. Furthermore, alternative sources of MSCs are required for patients with contraindications to autogenous cell therapy. The aim of this study was to evaluate the potential of mesenchymal cells from the human amniotic membrane (HAM) as a source of cells for allogeneic transplantation in bone regenerative therapy. Cells that retained a proliferative capacity of more than 50 population doubling level were distinguished from other HAM cells as HAM{alpha} cells and induced to osteogenic status-their in vivo osteogenesis was subsequently investigated in rats. It was found that HAM{alpha} cells were spindle shaped and were positive for MSC markers and negative for hematopoietic stem cell markers. Alkaline phosphatase activity and calcium deposition increased with osteogenic status of HAM{alpha} cells. The expression of osteocalcin mRNA was increased in HAM{alpha} cells cultured on calcium phosphate scaffolds. Moreover, xenografted HAM{alpha} cells remained viable and produced extracellular matrix for several weeks. Thus, this study suggests that human amniotic mesenchymal cells possess osteogenic differentiation potential and could be applied to allogeneic transplantation in bone regenerative therapy. - Highlights: Black-Right-Pointing-Pointer Human amniotic mesenchymal cells include cells (HAM{alpha} cells) that have the properties of MSCs. Black-Right-Pointing-Pointer HAM{alpha} cells have excellent osteogenic differentiation potential. Black-Right-Pointing-Pointer Osteogenic differentiation ability of HAM{alpha} was amplified by calcium phosphate scaffolds. Black-Right-Pointing-Pointer HAM{alpha} cells can be applicable to allogeneic cell transplantation in bone regenerative therapy.

  7. Suppression of the immune system as a critical step for bone formation from allogeneic osteoprogenitors implanted in rats

    NARCIS (Netherlands)

    Ganguly, Anindita; LaPointe, Vanessa; Alblas, Jacqueline; Chatterjea, Supriyo; van Blitterswijk, Clemens; de Boer, Jan

    2014-01-01

    The surface marker profile of mesenchymal stromal cells (MSCs) suggests that they can escape detection by the immune system of an allogeneic host. This could be an optimal strategy for bone regeneration applications, where off-the-shelf cells could be implanted to heal bone defects. However, it is

  8. Presence of Cells in Fresh-Frozen Allogeneic Bone Grafts from Different Tissue Banks.

    Science.gov (United States)

    Coutinho, Libério França; Amaral, Juliano Batista do; Santos, Érico Brito Dos; Martinez, Elizabeth Ferreira; Montalli, Victor Angelo M; Junqueira, José Luiz Cintra; Araújo, Vera Cavalcanti de; Napimoga, Marcelo Henrique

    2017-01-01

    Bone replacement materials have been widely used to reconstruct atrophic jawbones. Based on previous reports demonstrating the presence of viable cells in bone blocks even after processing by musculoskeletal tissue banks for orthopedic use, the aim of this study was to evaluate the presence of cells in bone blocks from three Brazilian tissue banks for maxillary reconstructions. All samples were processed by the respective tissue banks, according to the guidelines of the Brazilian National Sanitary Surveillance Agency. Three samples were removed from each block for subsequent histological processing and stained using hematoxylin & eosin. Further evaluation included section staining by the Feulgen method and ultrastructural analysis using scanning electron microscopy (SEM). Light microscopy images from all bone samples showed presence of osteocyte-like cells in all groups and intense Feulgen staining, demonstrating presence of DNA in bone even after tissue processing. The ultrastructural analysis showed red blood cells in lacunae within the bone tissue. In conclusion, despite bone tissue processing by the musculoskeletal tissue banks, cells may be found within the bone used for allogeneic grafts.

  9. Bronchiolitis obliterans after allogenic bone marrow transplantation: HRCT findings

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Jung Im; Jung, Won Sang; Hahn, Seong Tai; Park, Seog Hee [St. Mary' s Hospital, College of Medicine, Seoul (Korea, Republic of); Min, Chang Ki; Kim, Chun Choo [College of Medicine, The Catholic University, Seoul (Korea, Republic of)

    2004-06-15

    To evaluate the high resolution computed tomography (HRCT) findings of bronchiolitis obliterans (BO) after bone marrow transplantation (BMT). During the past three years, 11 patients were diagnosed as having BO after BMT when they developed irreversible air flow obstruction, with an FEV{sub 1} value of less than 80% of the baseline value, without any clinical evidence of infection. All 11 patients underwent HRCT, of whom eight also underwent follow-up HRCT. The HRCT images were assessed retrospectively for the presence of decreased lung attenuation, segmental or subsegmental bronchial dilatation, diminution of peripheral vascularity, centrilobular nodules, and branching linear structure on the inspiratory images. The lobar distribution of the decreased lung attenuation and bronchial dilatation was also examined. The presence of air trapping was investigated on the expiratory images. The interval changes of the HRCT findings were evaluated in those patients who had follow-up images. Abnormal HRCT findings were present in all cases; the most common abnormalities were decreased lung attenuation (n=11), subsegmental bronchial dilatation (n=6), diminution of peripheral vascularity (n=6), centrilobular nodules or branching linear structure (n=3), and segmental bronchial dilatation (n=3). Expiratory air trapping was noted in all patients. The decreased lung attenuation and bronchial dilatations were more frequent or extensive in the lower lobes. Interval changes were found in all patients with follow-up HRCT: increased extent of decreased lung attenuation (n=7); newly developed or progressed bronchial dilatation (n=4); and increased lung volume (n=3). HRCT scans are abnormal in patients with BO, with the most commonly observed finding being areas of decreased lung attenuation. While the HRCT findings are not specific, it is believed that their common features can assist in the diagnosis of BO in BMT recipients.

  10. Rehabilitation of atrophic maxilla using the combination of autogenous and allogeneic bone grafts followed by protocol-type prosthesis.

    Science.gov (United States)

    Margonar, Rogério; dos Santos, Pâmela Letícia; Queiroz, Thallita Pereira; Marcantonio, Elcio

    2010-11-01

    Currently, there are several techniques for the rehabilitation of atrophic maxillary ridges in literature. The grafting procedure using autogenous bone is considered ideal by many researchers, as it shows osteogenic capability and causes no antigenic reaction. However, this type of bone graft has some shortcomings, mainly the restricted availability of donor sites. In recent years, several alternatives have been investigated to supply the disadvantages of autogenous bone grafts. In such studies, allogeneic bone grafts, which are obtained from individuals with different genetic load, but from the same species, have been extensively used. They can be indicated in cases of arthroplasty, surgical knee reconstruction, large bone defects, and in oral and maxillofacial reconstruction. Besides showing great applicability and biocompatibility, this type of bone is available in unlimited quantities. On the other hand, allogeneic bone may have the disadvantage of transmitting infectious diseases. Atrophic maxillae can be treated with bone grafts followed by osseointegrated implants to obtain aesthetic and functional oral rehabilitation. This study aimed to show the viability of allogeneic bone grafting in an atrophic maxilla, followed by oral rehabilitation with dental implant and protocol-type prosthesis within a 3-year follow-up period by means of a clinical case report.

  11. Eye Movement Disorders Following Allogeneic Bone Marrow Transplantation on FK506 (Tacrolimus) and Ganciclovir.

    Science.gov (United States)

    Karagun, Barbaros S; Akbas, Tugana; Arpaci, Taner; Antmen, Bulent

    2018-01-01

    FK506 (tacrolimus) is an immunosuppressive drug and more potent than cyclosporine. FK506 is widely used for immunosuppression in the prevention and treatment of graft-versus-host disease after allogeneic bone marrow transplantation and solid organ transplantation. Neurotoxicity is a recognized complication of FK506 therapy, but ptosis and weakness of eye abduction unilaterally has not been reported in association with FK506 administration to date. We discuss a 13-year-old male patient who developed ptosis and weakness of eye abduction unilaterally 90 days after transplantation with bone marrow from an unrelated donor, for acute lymphoblastic leukemia in this case report. FK506 therapy was administered for graft-versus-host disease prophylaxis and CMV infection was treated with ganciclovir. The physical examination findings completely resolved 72 to 96 hours after concomitant FK506 and ganciclovir treatment were terminated.

  12. Correction of lysosomal enzyme deficiency in various organs of beta-glucuronidase-deficient mice by allogeneic bone marrow transplantation

    NARCIS (Netherlands)

    Hoogerbrugge, P. M.; Poorthuis, B. J.; Mulder, A. H.; Wagemaker, G.; Dooren, L. J.; Vossen, J. M.; van Bekkum, D. W.

    1987-01-01

    The correction of lysosomal enzyme deficiency was investigated for various organs of beta-glucuronidase-deficient C3H/Rij mice after allogeneic bone marrow transplantation from an enzymatically normal donor strain (C57BL/Rij). In the hemopoietic organs, the enzyme level increased to levels found in

  13. Treatment of Knee Osteoarthritis With Allogeneic Bone Marrow Mesenchymal Stem Cells: A Randomized Controlled Trial.

    Science.gov (United States)

    Vega, Aurelio; Martín-Ferrero, Miguel Angel; Del Canto, Francisco; Alberca, Mercedes; García, Veronica; Munar, Anna; Orozco, Lluis; Soler, Robert; Fuertes, Juan Jose; Huguet, Marina; Sánchez, Ana; García-Sancho, Javier

    2015-08-01

    Osteoarthritis is the most prevalent joint disease and a common cause of joint pain, functional loss, and disability. Conventional treatments demonstrate only modest clinical benefits without lesion reversal. Autologous mesenchymal stromal cell (MSC) treatments have shown feasibility, safety, and strong indications for clinical efficacy. We performed a randomized, active control trial to assess the feasibility and safety of treating osteoarthritis with allogeneic MSCs, and we obtain information regarding the efficacy of this treatment. We randomized 30 patients with chronic knee pain unresponsive to conservative treatments and showing radiological evidence of osteoarthritis into 2 groups of 15 patients. The test group was treated with allogeneic bone marrow MSCs by intra-articular injection of 40 × 10(6) cells. The control group received intra-articular hyaluronic acid (60 mg, single dose). Clinical outcomes were followed for 1 year and included evaluations of pain, disability, and quality of life. Articular cartilage quality was assessed by quantitative magnetic resonance imaging T2 mapping. Feasibility and safety were confirmed and indications of clinical efficacy were identified. The MSC-treated patients displayed significant improvement in algofunctional indices versus the active controls treated with hyaluronic acid. Quantification of cartilage quality by T2 relaxation measurements showed a significant decrease in poor cartilage areas, with cartilage quality improvements in MSC-treated patients. Allogeneic MSC therapy may be a valid alternative for the treatment of chronic knee osteoarthritis that is more logistically convenient than autologous MSC treatment. The intervention is simple, does not require surgery, provides pain relief, and significantly improves cartilage quality.

  14. An allogenic site-specific rat model of bone metastases for nuclear medicine and experimental oncology.

    Science.gov (United States)

    Biesalski, Barbara; Yilmaz, Bengü; Buchholz, Hans-Georg; Bausbacher, Nicole; Schreckenberger, Mathias; Thews, Oliver

    2012-05-01

    Bone metastases are a major problem in several tumor entities affecting the therapeutic decision and the patient's prognosis. Single photon emission computed tomography (SPECT) and positron emission tomography (PET) are promising techniques for identifying bone tumors using gamma- or positron-emitting labeled radiotracers, but the same tracers if labeled with beta-emitters may also be used to apply therapeutic radionuclides for localized irradiation. For the tracer development specifically accumulating in osseous lesions, animal models of bone metastasis are needed. A technique was developed for tumor cell injection into the circulation of the hind limb of rats. For tumor implantation, the arteria epigastrica caudalis superficialis (a branch of the femoral artery) was cannulated, and 2×10(5) cells were injected. By using the allogenic Walker 256 mammary carcinoma cell line, isolated bone metastases were induced. For visualizing of the tumor growth, PET with 18F-fluoride was performed weekly on a μ-PET system. After 2-3 weeks, tumor invasion was confirmed by histology. Three weeks after tumor cell inoculation, PET images showed signs of bone metastases in 9 out of 11 animals. The tumors were located either in the proximal tibia/fibula or in the distal femur. At this time, the animals showed no restrictions in mobility. The tumors grew constantly over time. The final histological analysis showed tumors growing invasively into the bone matrix. With this model, new SPECT or PET tracers can be evaluated for their potency of accumulating in bone metastases in vivo and to determine which are therefore suitable for diagnosis and/or therapy. Copyright © 2012. Published by Elsevier Inc.

  15. Dichotomous role of interferon-gamma in allogeneic bone marrow transplant.

    Science.gov (United States)

    Lu, Ying; Waller, Edmund K

    2009-11-01

    Interferon (IFN)-gamma is a pleiotropic cytokine with a central role in innate and adaptive immunity. As a potent pro-inflammatory and antitumor cytokine, IFN-gamma is conventionally thought to be responsible for driving cellular immune response. On the other hand, accumulating evidence suggests that IFN-gamma also has immunosuppressive activity. An important role for IFN-gamma in inhibiting graft-versus-host disease (GVHD) has been demonstrated in murine models, despite IFN-gamma being one of the key factors amplifying T cell activation during the process of acute GVHD (aGVHD), the major complication and cause of post-transplant mortality in allogeneic bone marrow transplantation (BMT). At the same time, IFN-gamma facilitates graft-versus-leukemia (GVL) activity. Dissociation of GVL effects from GVHD has been the ultimate goal of allogeneic BMT in the treatment of hematologic malignancies. This paradoxic role of IFN-gamma makes modulating its activity a promising strategy to maximize GVL while minimizing GVHD and improve clinical outcomes in BMT. In this review, the effects of IFN-gamma on GVHD and GVL are discussed with consideration of the mechanism of IFN-gamma action.

  16. Naso-jejunal feeding in allogeneic bone marrow transplant recipients: results of a pilot study.

    Science.gov (United States)

    Sefcick, A; Anderton, D; Byrne, J L; Teahon, K; Russell, N H

    2001-12-01

    Patients undergoing allogeneic bone marrow transplants (BMT) are often malnourished prior to commencing the procedure. They face intensive treatment with often marked nutritional consequences. There is no consensus on the optimal nutritional management of these patients. Elective parenteral nutrition (PN), beginning pre-transplant irrespective of the patients nutritional status, or the use of "salvage" PN, beginning during the post-transplant period if the patient fails to maintain nutritional status with oral diet, have been used. Enteral nutrition may benefit the patient by maintaining nutritional support throughout the transplant period, avoiding the complications and expense of PN and possibly, by using specific diets, protecting the gastrointestinal tract from the effects of chemoradiation. However, naso-gastric feeding during a transplant is not without risks, including the safe insertion of a tube in patients with mucositis and pan-cytopenias, tube displacement by vomiting and aspiration from gastro-oesophageal reflux. An alternative approach is to use naso-jejunal (NJ) feeding tubes which are associated with less risk of loss due to vomiting and less risk of aspiration. We report a pilot study of 15 allogeneic BMT patients who had elective NJ feeding initiated before conditioning therapy irrespective of perceived nutritional compromise. This was well tolerated and feasible with a motivated nutritional team.

  17. Acute Fibrinous and Organizing Pneumonia Associated With Allogenic Hematopoietic Stem Cell Transplant Successfully Treated With Corticosteroids

    Directory of Open Access Journals (Sweden)

    Lam-Phuong Nguyen DO

    2016-04-01

    Full Text Available Acute fibrinous and organizing pneumonia (AFOP is an extremely rare, relatively new, and distinct histological pattern of acute lung injury characterized predominately by the presence of intra-alveolar fibrin and associated organizing pneumonia. AFOP may be idiopathic or associated with a wide spectrum of clinical conditions. It has a variable clinical presentation from mild respiratory symptoms to that similar to the acute respiratory distress syndrome. Currently there is no consensus on treatment, and corticosteroids previously were of unclear benefit. To date, there are less than 40 cases of AFOP reported in the literature and only one has been linked to hematopoietic stem cell transplantation. Here we report the first case series of 2 patients who developed AFOP following allogenic stem cell transplant that were successfully treated with high-dose corticosteroids.

  18. Systematic analysis on the efficacy of bone enhancement methods used for success in dental implants.

    Science.gov (United States)

    Elakkiya, S; Ramesh, A S; Prabhu, K

    2017-01-01

    Bone grafting is beneficial in enhancing bones that are lost due to trauma or natural or pathologic process. Autogenous bone, allogenic bone, xenogeneic bone, bone substitutes, and alloplasts can also be used for this purpose. Bone quantity should be adequate for the placement of implants, which necessitate the use of bone grafts before implant placement. This review analyses the different bone graft materials that are used for grafting around implants and evaluate if these grafts yield successful implant osseointegration over a period of time. The MEDLINE-PubMed database was searched from September 2016 to 10 years previously. Several journals were hand searched and from cross-references. The primary outcome measure that was analyzed was the survival rate of dental implants in the grafted sites at 6 months-1 year, and the secondary outcomes were success rates of dental implants over a period of 3-5 years' follow-up. The search yielded 213 articles. Ultimately, 31 studies meeting the eligibility criteria were selected. The analysis shows that autologous bone grafts can be preferred over allografts and xenografts for grafting implant sites, which showed less complication and high success rate. Based on the available data in the current existing studies with a follow-up period of at least 3-5 years, it can be summarized that the autologous bone grafts can be preferred over allografts and xenografts for grafting implant sites since they are stable for at least 3-5 years.

  19. HLA-typing analysis following allogeneic bone grafting for sinus lifting.

    Science.gov (United States)

    Piaia, Marcelo; Bub, Carolina Bonet; Succi, Guilherme de Menezes; Torres, Margareth; Costa, Thiago Henrique; Pinheiro, Fabricio Costa; Napimoga, Marcelo Henrique

    2017-03-01

    According to the Brazilian Association of Organ Transplants, in 2015, 19,408 bone transplants were performed in Brazil, over 90% by Dental Surgeons. The surgical technique itself has a respectable number of reports regarding its clinical efficacy, as measured by long-term survival of dental implants in grafted areas. Uncertainty remains, however, as to whether fresh frozen grafts from human bone donors remain immunologically innocuous in the body of the host. Six male with no previous medical history of note, including systemic diseases, surgery or blood transfusion were selected. These patients underwent reconstructive procedures (sinus lifting) using fresh frozen human bone from a tissue bank. All patients had venous blood samples collected prior to surgery and 6 months after the procedure. Anti-HLA analysis for the detection of HLA (human leukocyte antigen) antibodies was performed using methods such as the LABScreen PRA Class I and Class II, LABScreen Single Antigen Class I and Class II, Luminex Platform. Reactive individuals to the screening tests (LABScreen PRA) were further investigated to determine the specificity of the antibodies detected (LABScreen Single Antigen) with a cutoff value of median fluorescence intensity ≥500. As a result, it was observed that two patients (33%) were positive in screening tests, one presenting with anti-HLA Class I and II sensitization and the other with anti-HLA class II. The specificity analysis showed that the patients sensitized to HLA class II presented 4 specificities, 3 of which immunologically relevant. In the second individual, 23 specificities were identified, 6 of which immunologically important for HLA class I and 4 specificities for HLA class II, 3 of these were immunologically important. All specificities detected had average fluorescence. These findings are suggestive that sinus-lifting procedures with allogeneic bone can induce immunological sensitization.

  20. Tendon Reattachment to Bone in an Ovine Tendon Defect Model of Retraction Using Allogenic and Xenogenic Demineralised Bone Matrix Incorporated with Mesenchymal Stem Cells.

    Directory of Open Access Journals (Sweden)

    Tanujan Thangarajah

    Full Text Available Tendon-bone healing following rotator cuff repairs is mainly impaired by poor tissue quality. Demineralised bone matrix promotes healing of the tendon-bone interface but its role in the treatment of tendon tears with retraction has not been investigated. We hypothesized that cortical demineralised bone matrix used with minimally manipulated mesenchymal stem cells will result in improved function and restoration of the tendon-bone interface with no difference between xenogenic and allogenic scaffolds.In an ovine model, the patellar tendon was detached from the tibial tuberosity and a complete distal tendon transverse defect measuring 1 cm was created. Suture anchors were used to reattach the tendon and xenogenic demineralised bone matrix + minimally manipulated mesenchymal stem cells (n = 5, or allogenic demineralised bone matrix + minimally manipulated mesenchymal stem cells (n = 5 were used to bridge the defect. Graft incorporation into the tendon and its effect on regeneration of the enthesis was assessed using histomorphometry. Force plate analysis was used to assess functional recovery.Compared to the xenograft, the allograft was associated with significantly higher functional weight bearing at 6 (P = 0.047, 9 (P = 0.028, and 12 weeks (P = 0.009. In the allogenic group this was accompanied by greater remodeling of the demineralised bone matrix into tendon-like tissue in the region of the defect (p = 0.015, and a more direct type of enthesis characterized by significantly more fibrocartilage (p = 0.039. No failures of tendon-bone healing were noted in either group.Demineralised bone matrix used with minimally manipulated mesenchymal stem cells promotes healing of the tendon-bone interface in an ovine model of acute tendon retraction, with superior mechanical and histological results associated with use of an allograft.

  1. Safety of allogeneic bone marrow derived mesenchymal stromal cell therapy in renal transplant recipients: the neptune study.

    Science.gov (United States)

    Reinders, Marlies E J; Dreyer, Geertje J; Bank, Jonna R; Roelofs, Helene; Heidt, Sebastiaan; Roelen, Dave L; Zandvliet, Maarten L; Huurman, Volkert A L; Fibbe, Wim E; van Kooten, Cees; Claas, Frans H J; Rabelink, Ton J; de Fijter, Johan W

    2015-11-04

    Mesenchymal stromal cells (MSC) may serve as an attractive therapy in renal transplantation due to their immunosuppressive and reparative properties. While most studies have used autologous MSCs, allogeneic MSCs offer the advantage of immediate availability for clinical use. This is of major importance for indications where instant treatment is needed, for example allograft rejection or calcineurin inhibitor toxicity. Clinical studies using allogeneic MSCs are limited in number. Although these studies showed no adverse reactions, allogeneic MSCs could possibly elicit an anti-donor immune response, which may increase the incidence of rejection and impact the allograft survival in the long term. These safety issues should be addressed before further studies are planned with allogeneic MSCs in the solid organ transplant setting. 10 renal allograft recipients, 18-75 years old, will be included in this clinical phase Ib, open label, single center study. Patients will receive two doses of 1.5 × 10(6) per/kg body weight allogeneic bone marrow derived MSCs intravenously, at 25 and 26 weeks after transplantation, when immune suppression levels are reduced. The primary end point of this study is safety by assessing biopsy proven acute rejection (BPAR)/graft loss after MSC treatment. Secondary end points, all measured before and after MSC infusions, include: comparison of fibrosis in renal biopsy by quantitative Sirius Red scoring; de novo HLA antibody development and extensive immune monitoring; renal function measured by cGFR and iohexol clearance; CMV and BK infection and other opportunistic infections. This study will provide information on the safety of allogeneic MSC infusion and its effect on the incidence of BPAR/graft loss. NCT02387151.

  2. Allogeneic versus autologous derived cell sources for use in engineered bone-ligament-bone grafts in sheep anterior cruciate ligament repair.

    Science.gov (United States)

    Mahalingam, Vasudevan D; Behbahani-Nejad, Nilofar; Horine, Storm V; Olsen, Tyler J; Smietana, Michael J; Wojtys, Edward M; Wellik, Deneen M; Arruda, Ellen M; Larkin, Lisa M

    2015-03-01

    The use of autografts versus allografts for anterior cruciate ligament (ACL) reconstruction is controversial. The current popular options for ACL reconstruction are patellar tendon or hamstring autografts, yet advances in allograft technologies have made allogeneic grafts a favorable option for repair tissue. Despite this, the mismatched biomechanical properties and risk of osteoarthritis resulting from the current graft technologies have prompted the investigation of new tissue sources for ACL reconstruction. Previous work by our lab has demonstrated that tissue-engineered bone-ligament-bone (BLB) constructs generated from an allogeneic cell source develop structural and functional properties similar to those of native ACL and vascular and neural structures that exceed those of autologous patellar tendon grafts. In this study, we investigated the effectiveness of our tissue-engineered ligament constructs fabricated from autologous versus allogeneic cell sources. Our preliminary results demonstrate that 6 months postimplantation, our tissue-engineered auto- and allogeneic BLB grafts show similar histological and mechanical outcomes indicating that the autologous grafts are a viable option for ACL reconstruction. These data indicate that our tissue-engineered autologous ligament graft could be used in clinical situations where immune rejection and disease transmission may preclude allograft use.

  3. Total Body Irradiation for Allogeneic Bone Marrow Transplantation in Chronic Myelogenous Leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Su Mi; Choi, Ihl Bohng; Kang, Ki Mun; Kim, In Ah; Shinn, Kyung Sub; Kim, Choon Choo; Kim, Dong Jip [Catholic University College of Medicine, Seoul (Korea, Republic of)

    1994-06-15

    Between July 1987 and December 1992, we treated 22 patients with chromic myelogenous leukemia; 14 in the chronic phase and 8 with more advanced disease. All were received with allogeneic bone marrow transplantation from HLA-identical sibling donors after a total body irradiation (TBI) cyclophosphamide conditioning regimen. Patients were non-randomly assigned to either 1200 cGy/6 fractions/3 days (6 patients) or 1320 cGy/8 fractions/4 days (16 patients) by dose of TBI. Of the 22 patients, 8 were prepared with cyclophosphamide alone, 14 were conditioned with additional adriamycin or daunorubicin. To prevent graft versus host disease, cyclosporine was given either alone or in conjunction with methotrexate. The actuarial survival and leukemic-free survival at four years were 58.5% and 41.2%, respectively, and the relapse rate was 36% among 22 patients. There was a statistically significant difference in survival between the patients in chronic phase and more advanced phase (76% vs 33%, p=0.05). The relapse rate of patients receiving splenectomy was higher than that of patients receiving splenic irradiation (50% vs 0%, p=0.04). We conclude that the probability of cure is highest if transplantation is performed while the patient remains in the chronic phase.

  4. Second Allogeneic Hematopoietic Cell Transplantation for Patients with Fanconi Anemia and Bone Marrow Failure

    NARCIS (Netherlands)

    Ayas, Mouhab; Eapen, Mary; Le-Rademacher, Jennifer; Carreras, Jeanette; Abdel-Azim, Hisham; Alter, Blanche P.; Anderlini, Paolo; Battiwalla, Minoo; Bierings, MB; Buchbinder, David K.; Bonfim, Carmem; Camitta, Bruce M.; Fasth, Anders L.; Gale, Robert Peter; Lee, Michelle A.; Lund, Troy C.; Myers, Kasiani C.; Olsson, Richard F.; Page, Kristin M.; Prestidge, Tim D.; Radhi, Mohamed; Shah, Ami J.; Schultz, Kirk R.; Wirk, Baldeep; Wagner, John E.; Deeg, H. Joachim

    2015-01-01

    A second allogeneic hematopoietic cell transplantation (HCT) is the sole salvage option for individuals who develop graft failure after their first HCT. Data on outcomes after second HCT in patients with Fanconi anemia (FA) are scarce. Here we report outcomes after second allogeneic HCT for FA (n =

  5. The availability of full match sibling donors and feasibility of allogeneic bone marrow transplantation in Brazil

    Directory of Open Access Journals (Sweden)

    Eid K.A.B.

    2003-01-01

    Full Text Available The feasibility of allogeneic bone marrow transplantation (alloBMT in a developing country has not yet been demonstrated. Many adverse factors including social and economic limitations may reduce the overall results of this complex and expensive procedure. Our objective was to characterize the most important clinical, social and economic features of candidates for transplantation and their potential donors as well as the influence of these factors on overall survival in a retrospective and exploratory analysis at a university hospital. From July 1993 to July 2001, candidates for BMT were referred to the Bone Marrow Transplantation Unit by Hematology and Oncology Centers from several regions of Brazil. A total of 1138 patients were referred to us as candidates for alloBMT. Median age was 25 years (range: 2 months-60 years, 684 (60.1% were males and 454 (39.9% were females. The clinical indications were severe aplastic anemia and hematological malignancies. From the total of 1138 patients, 923 had HLA-typing; 497/923 (53.8% candidates had full match donors; 352/1138 (30.8% were eligible for alloBMT. Only 235 of 352 (66.7% were transplanted. Schooling was 1st to 8th grade for 123/235 (52.3%; monthly family income ranged from US$60 (7% to more than US$400 (36%. Overall survival for patients with chronic myeloid leukemia, severe aplastic anemia and acute myeloid leukemia was 58, 60 and 30%, respectively. Thus, overall survival rates for the most frequent hematological diseases were similar to those reported in the International Registry, except for acute myeloid leukemia. This descriptive and exploratory analysis suggests the feasibility of alloBMT in a developing country like Brazil.

  6. Colon biopsies for evaluation of acute graft-versus-host disease (A-GVHD in allogeneic bone marrow transplant patients

    Directory of Open Access Journals (Sweden)

    Kampalath Bal

    2003-03-01

    Full Text Available Abstract Background Proper histomorphological interpretation of intestinal acute graft versus host disease (A-GVHD associated with allogeneic bone marrow transplantation (BMT is critical for clinical managaement. However, studies methodically evaluating different histomorphological features of A-GVHD are rare. Methods Colonic biopsies from 44 allogeneic BMT patients having biopsy-proven cutaneous A-GVHD were compared with colon biopsies from 48 negative controls. Results A-GVHD showed intra-cryptal apoptosis in 91% and pericryptal apoptosis in adjacent lamina propria in 70% (p Conclusions Intracyptal apoptosis is a reliable indicator of A-GVHD. Its diagnostic significance was improved if intracyptal apoptosis was associated with features which were observed more frequently in A-GVHD group as mentioned above.

  7. Persistence of donor-derived protein in host myeloid cells after induced rejection of engrafted allogeneic bone marrow cells

    Science.gov (United States)

    Saito, Toshiki I.; Fujisaki, Joji; Carlson, Alicia L.; Lin, Charles P.; Sykes, Megan

    2014-01-01

    Objective In recipients of allogeneic hematopoietic stem cell transplantation to treat hematologic malignancies, we have unexpectedly observed anti-tumor effects in association with donor cell rejection in both mice and humans. Host-type CD8 T cells were shown to be required for these anti-tumor effects in the murine model. Since sustained host CD8 T cell activation was observed in the murine bone marrow following the disappearance of donor chimerism in the peripheral blood, we hypothesized that donor antigen presentation in the bone marrow might be prolonged. Materials and Methods To assess this hypothesis, we established mixed chimerism with green fluorescence protein (GFP)-positive allogeneic bone marrow cells, induced rejection of the donor cells by giving recipient leukocyte infusions (RLI), and utilized in vivo microscopy to follow GFP-positive cells. Results After peripheral donor leukocytes disappeared, GFP persisted within host myeloid cells surrounding the blood vessels in the bone marrow, suggesting that the host myeloid cells captured donor-derived GFP protein. Conclusions Since the host-versus-graft reaction promotes the induction of anti-tumor responses in this model, this retention of donor-derived protein may play a role in the efficacy of RLI as an anti-tumor therapy. PMID:20167247

  8. Delayed non-infectious lung disease in allogeneic bone marrow transplant recipients.

    Science.gov (United States)

    Trisolini, R; Stanzani, M; Lazzari Agli, L; Colangelo, A; Bonifazi, F; Falcioni, S; Patelli, M; Falcone, F; Bandini, G; Tura, S; Poletti, V

    2001-03-01

    The studies on late-onset non-infectious respiratory complications after allogeneic bone marrow transplantation (allo-BMT) have been mainly focused on bronchiolitis obliterans to date. The aim of this work was to analyze the incidence, clinico-pathologic characteristics and outcome of the entire spectrum of entities falling into the group of delayed non-infectious lung disease (DLD). Retrospective chart review was carried out of 112 patients who underwent allo-BMT for hematologic malignancies between April 1995 and November 1998 at a single Institution. The categorization of the pulmonary disease was made by analyzing clinical data, bronchoalveolar lavage (BAL), high-resolution computed tomography (HRCT) and histology when possible. DLD occurred in 10 (10%) out of 97 recipients who survived at least 100 days following allo-BMT and was defined as bronchiolitis obliterans (BO; 4 cases), acute lung injury (ALI; 1 case) and subacute cellular interstitial pneumonia (SCIP; 5 cases). The BAL-profile was characterized by a marked increase of the neutrophil percentage in BO cases and of the lymphocyte (predominantly CD8+) percentage in parenchymal DLDs (SCIP, ALI). HRCT proved to be helpful to correctly identify BO cases, whereas histology was always needed to better define DLD presenting with an interstitial and/or alveolar pattern. The predominant airway involvement as well as the acute-onset of a respiratory illness with histological evidence of diffuse alveolar damage were associated with a worse prognosis because of a poor response to the immunosuppressive treatment. DLDs represent a group of entities heterogeneous in regard to variables such as onset and clinical behaviour (acute, subacute or chronic), predominant pattern of lung involvement (airway or parenchymal), response to treatment. Although immunopathologic mechanisms related to c-GVHD probably have a relevant pathogenic importance in this setting, the possible role of associated events (eg, drug toxicity and

  9. Dynamic of bone marrow fibrosis regression predicts survival after allogeneic stem cell transplantation for myelofibrosis.

    Science.gov (United States)

    Kröger, Nicolaus; Zabelina, Tatjana; Alchalby, Haefaa; Stübig, Thomas; Wolschke, Christine; Ayuk, Francis; von Hünerbein, Natascha; Kvasnicka, Hans-Michael; Thiele, Jürgen; Kreipe, Hans-Heinrich; Büsche, Guntram

    2014-06-01

    We correlate regression of bone marrow fibrosis (BMF) on day 30 and 100 after dose- reduced allogeneic stem cell transplantation (allo-SCT) in 57 patients with primary or post-essential thrombocythemia/polycythemia vera myelofibrosis with graft function and survival. The distribution of International Prognostic Scoring System (IPSS) risk score categories was 1 patient with low risk, 5 patients with intermediate-1 risk, 18 patients with intermediate-2 risk, and 33 patients with high risk. Before allo-SCT, 41 patients (72%) were classified as XXX [myclofibrosis (MF)]-3 and 16 (28%) were classified as MF-2 according to the World Health Organization criteria. At postengraftment day +30 (±10 days), 21% of the patients had near-complete or complete regression of BMF (MF-0/-1), and on day +100 (±20 days), 54% were MF-0/-1. The 5-year overall survival rate at day +100 was 96% in patients with MF-0/-1 and 57% for those with MF-2/-3 (P = .04). There was no difference in BMF regression at day +100 between IPSS high-risk and low/intermediate-risk patients. Complete donor cell chimerism at day +100 was seen in 81% of patients with MF-0/-1 and in 31% of those with MF-2/-3. Patients with MF-2/-3 at day +100 were more likely to be transfusion-dependent for either RBCs (P = .014) or platelets (P = .018). Rapid BMF regression after reduced-intensity conditioning allo-SCT resulted in a favorable survival independent of IPSS risk score at transplantation. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  10. Histomorhological and clinical evaluation of maxillary alveolar ridge reconstruction after craniofacial trauma by applying combination of allogeneic and autogenous bone graft

    Directory of Open Access Journals (Sweden)

    Francesco Saverio De Ponte

    2017-02-01

    Full Text Available A variety of techniques and materials for the rehabilitation and reconstruction of traumatized maxillary ridges prior to dental implants placement have been described in literature. Autogenous bone grafting is considered ideal by many researchers and it still remains the most predictable and documented method. The aim of this report is to underline the effectiveness of using allogeneic bone graft for managing maxillofacial trauma. A case of a 30-year-old male with severely atrophic maxillary ridge as a consequence of complex craniofacial injury is presented here. Augmentation procedure in two stages was performed using allogeneic and autogenous bone grafts in different areas of the osseous defect. Four months after grafting, during the implants placement surgery, samples of both sectors were withdrawn and submitted to histological evaluation. On the examination of the specimens, treated by hematoxylin and eosin staining, the morphology of integrated allogeneic bone grafts was revealed to be similar to the autologous bone. Our clinical experience shows how the allogeneic bone graft presented normal bone tissue architecture and is highly vascularized, and it can be used for reconstruction of severe trauma of the maxilla.

  11. Histomorhological and clinical evaluation of maxillary alveolar ridge reconstruction after craniofacial trauma by applying combination of allogeneic and autogenous bone graft.

    Science.gov (United States)

    De Ponte, Francesco Saverio; Falzea, Roberto; Runci, Michele; Siniscalchi, Enrico Nastro; Lauritano, Floriana; Bramanti, Ennio; Cervino, Gabriele; Cicciu, Marco

    2017-02-01

    A variety of techniques and materials for the rehabilitation and reconstruction of traumatized maxillary ridges prior to dental implants placement have been described in literature. Autogenous bone grafting is considered ideal by many researchers and it still remains the most predictable and documented method. The aim of this report is to underline the effectiveness of using allogeneic bone graft for managing maxillofacial trauma. A case of a 30-year-old male with severely atrophic maxillary ridge as a consequence of complex craniofacial injury is presented here. Augmentation procedure in two stages was performed using allogeneic and autogenous bone grafts in different areas of the osseous defect. Four months after grafting, during the implants placement surgery, samples of both sectors were withdrawn and submitted to histological evaluation. On the examination of the specimens, treated by hematoxylin and eosin staining, the morphology of integrated allogeneic bone grafts was revealed to be similar to the autologous bone. Our clinical experience shows how the allogeneic bone graft presented normal bone tissue architecture and is highly vascularized, and it can be used for reconstruction of severe trauma of the maxilla. Copyright © 2017 Daping Hospital and the Research Institute of Surgery of the Third Military Medical University. Production and hosting by Elsevier B.V. All rights reserved.

  12. Natural killer function following allogeneic bone marrow transplantation. Very early reemergence but strong dependence of cytomegalovirus infection

    DEFF Research Database (Denmark)

    Hokland, M; Jacobsen, N; Ellegaard, J

    1988-01-01

    Natural killer (NK) cell function was followed sequentially after allogeneic bone marrow transplantation (BMT) using three approaches: (1) chromium-release assay with purified mononuclear effector cells, (2) chromium-release assay with whole blood effectors, and 3) enumeration of lymphocytes...... bearing the NK-associated antigen NKH-1 (N901). The two latter methods enabled us to demonstrate a very early reappearance (at day 4 posttransplant) of pre-NK cells, which after interferon-alpha enhancement effectively lysed K562 cells and carried the NKH-1 antigen. During the first month NK function...

  13. Allogeneic mesenchymal stem cells and xenogenic platelet rich plasma, associated or not, in the repair of bone failures in rabbits with secondary osteoporosis.

    Science.gov (United States)

    Rocha, Mariá Andrade de Carvalho; Silva, Laís Meireles Costa; Oliveira, Wellson Andrade de; Bezerra, Dayseanny de Oliveira; Silva, Gustavo Cardoso da; Silva, Lucilene Dos Santos; Medeiros, Brenda Lurian do Nascimento; Baêta, Sílvia de Araújo França; Carvalho, Maria Acelina Martins de; Argôlo, Napoleão Martins

    2017-09-01

    To assess the efficacy of allogeneic mesenchymal stem cells and xenogenic platelet rich plasma in the treatment of bone failure of osteoporotic rabbits secondary to estrogenic deprivation and iatrogenic hypercortisolism. Eight female rabbits underwent ovarian resection and corticoid therapy to induce clinical status of osteoporosis. Four failures were produced in the tibiae, with each failure being treated with hemostatic sponge, allogenic mesenchymal stem cells, xenogenic platelet-rich plasma and the association between both. The animals were divided into two groups, evaluated radiographically and histopathologically at 30 and 60 days post treatment. A radiographically confirmed consolidation of bone failures treated with allogeneic mesenchymal stem cells, associated with the histopathological image of mature and immature bone tissue, without evidence of osteopenia, was compared with the other groups, in which radiolucent failures with osteopenia and fibrosis were still present, denoting the satisfactory effect of the first treatment in detriment to the others. The treatment of bone failures of rabbits with secondary osteoporosis with allogeneic mesenchymal stem cells induced greater bone consolidation with mature and immature bone tissue production (p<0.01), when compared to the other treatments.

  14. Successful management of immunological rejection following allogeneic simple limbal epithelial transplantation (SLET) for bilateral ocular burns.

    Science.gov (United States)

    Bhalekar, Swapnil; Basu, Sayan; Sangwan, Virender S

    2013-03-14

    A 41-year-old woman presented with bilateral total limbal stem cell deficiency, one year after chemical injury. She underwent allogeneic simple limbal epithelial transplantation (SLET) from a cadaveric donor in her right eye. One month later her unaided visual acuity (VA) improved to 20/100 from hand-motions. The corneal surface was avascular and epithelialised. Three months later, she presented with acute pain in right eye with peripheral corneal neovascularisation encircling the transplants, engorged and tortuous perilimbal vessels and diffuse epithelial haze. For a diagnosis of allograft rejection, pulse doses of intravenous methyl prednisolone with intensive topical steroids were administered. Her symptoms resolved in a week, confirming the diagnosis. She recovered her pre-rejection VA. She was maintained on systemic immunosuppressive agents. Her ocular surface continues to be stable. This case describes hitherto unknown clinical features of allograft rejection following SLET and emphasises the importance of continued immunosuppression in allogeneic limbal transplantation.

  15. Targeted bone marrow radioablation with 153Samarium-lexidronam promotes allogeneic hematopoietic chimerism and donor-specific immunologic hyporesponsiveness.

    Science.gov (United States)

    Inverardi, Luca; Linetsky, Elina; Pileggi, Antonello; Molano, R Damaris; Serafini, Aldo; Paganelli, Giovanni; Ricordi, Camillo

    2004-03-15

    Transplantation tolerance, defined as acceptance of a graft by an otherwise fully immunocompetent host, has been an elusive goal. Although robust tolerance has been achieved by the induction of stable hematopoietic chimerism after bone marrow transplantation, lethal or sublethal radiation conditioning used to induce long-term chimerism precludes its clinical use. We studied whether targeted delivery of radiation to bone marrow could allow for bone marrow cell (BMC) engraftment, chimerism, and donor-specific tolerance in the absence of the side effects associated with external irradiation. We administered a radioactive bone-seeking compound (Samarium-Lexidronam, Quadramet, Berlex Laboratories, Wayne, NJ) together with transient T-cell costimulatory blockade to recipient mice. Allogeneic BMCs were given 7 or 14 days after preconditioning. Costimulatory blockade was obtained by the use of an anti-CD154 antibody for 4 weeks. Chimerism was assessed by flow cytometry. Mice then received donor-specific and third-party skin grafts. Graft survival was analyzed with mechanisms of donor-specific hyporesponsiveness. High levels of stable chimerism across an allogeneic barrier were achieved in mice by a single administration of Samarium-Lexidronam, transient T-cell costimulatory blockade, and BMC transplantation. A large percentage of chimeric animals retained donor-derived skin grafts for more than 120 days without requiring additional immunosuppression, suggesting that harsh cytotoxic preconditioning is not necessary to achieve stable chimerism and donor specific hyporesponsiveness. Analysis of the T-cell repertoire in chimeras indicates T-cell deletional mechanisms. These data broaden the potential use of BMC transplantation for tolerance induction and argue for its potential in treating autoimmune diseases.

  16. The effect of allogenic versus autologue mesenchymal stem cells in bone reconstructio

    DEFF Research Database (Denmark)

    Jensen, Stefan; Overgaard, Søren; Ding, Ming

    2008-01-01

    with allogenic MSC (group#3) proved to have a significant higher mean SFE (Fisher's LSD-test). The other groups (#1 and #2) had a slightly higher mean SFE (Table 2). Discussion and Conclusion: There are shown two interesting things in this minor pilot-study. There is a trend showing, that the use of MSC has...

  17. Brain MR imaging abnormalities in pediatric patients after allogeneic bone marrow transplantation

    Directory of Open Access Journals (Sweden)

    Sally Emad-Eldin

    2014-12-01

    Conclusion: CNS complications after allogenic BMT in pediatric patients could cause a significant clinical problem. MRI can provide early diagnosis and follow-up to monitor treatment changes. Knowing the onset of the presentation of the complication in relation to the chronology of the transplant is important as it provides significant guidance on which causes to consider.

  18. The immunodeficiency of bone marrow-transplanted patients. II. CD8-related suppression by patient lymphocytes of the response of donor lymphocytes to mitogens, antigens, and allogeneic cells

    DEFF Research Database (Denmark)

    Ødum, Niels; Hofmann, B; Jacobsen, N

    1987-01-01

    Lymphocytes from 21 patients sampled 1-6 months after bone marrow transplantation (BMT) were tested for functional suppressor activity against marrow-donor lymphocytes in the lymphocyte transformation test. Suppression of donor responses to allogeneic (i.e. mixed lymphocyte reaction, MLR...

  19. Complications with allogeneic, cancellous bone blocks in vertical alveolar ridge augmentation: prospective clinical case study and review of the literature.

    Science.gov (United States)

    Draenert, Florian G; Kämmerer, Peer W; Berthold, Michael; Neff, Andreas

    2016-08-01

    Vertical bone augmentation in dental implantology is an indication for cancellous allogeneic bone blocks (ABB). However, these materials may lead to adverse reactions, which are known well in orthopedics but rarely published. Therefore, in this study, we performed an evaluation of the use of ABB in vertical bone augmentation in clinical dental implantology. The prospective clinical study included 20 cases with vertical augmentation using ABB and subsequent or simultaneous placement of implants in the lateral maxilla and mandible. Follow-up included panoramic radiography, tissue healing, and peri-implantitis. Because of the limited number of patients, the report was planned to be descriptive only. Loss of ABB or peri-implantitis of more than 30% of the intraosseous implant length was deemed to indicate failure. The study was cancelled after six cases because of an unexpectedly high number of complications (5 of 6; 83%). The average surveillance time was 1460 days. Three types of unsatisfying outcome were observed: type I, early complete loss of the augmentation with soft tissue defects after 3 to 8 weeks (n = 2); type II, early soft tissue maceration (up to 8 weeks) without loss of coverage and complete early bone healing with later peri-implantitis and bone loss after prosthetic loading (6 months or later; n = 2); and type III, complication-free bone healing with subsequent peri-implantitis after prosthetic loading (6 months or later; n = 1). Complications were observed in vertical augmentation with ABB and implant placement. After careful consideration, literature data were found to support these results and also suggest that tissue level implants may be advantageous in vertical bone augmentation with ABB. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Potential benefits of allogeneic bone marrow mesenchymal stem cells for wound healing.

    Science.gov (United States)

    Badiavas, Alexander R; Badiavas, Evangelos V

    2011-11-01

    It is becoming increasingly evident that select adult stem cells have the capacity to participate in repair and regeneration of damaged and/or diseased tissues. Mesenchymal stem cells have been among the most studied adult stem cells for the treatment of a variety of conditions, including wound healing. Mesenchymal stem cell features potentially beneficial to cutaneous wound healing applications are reviewed. Given their potential for in vitro expansion and immune modulatory effects, both autologous and allogeneic mesenchymal stem cells appear to be well suited as wound healing therapies. Allogeneic mesenchymal stem cells derived from young healthy donors could have particular advantage over autologous sources where age and systemic disease can be significant factors.

  1. Long-term outcomes of the use of allogeneic, radiation-sterilised bone blocks in reconstruction of the atrophied alveolar ridge in the maxilla and mandible

    OpenAIRE

    Krasny, Marta; Krasny, Kornel; Fiedor, Piotr; Zadurska, Ma?gorzata; Kami?ski, Artur

    2015-01-01

    Increasingly dental surgeons face the challenge of reconstruction of the height and/or thickness of the alveolar ridge as more and more patients wish to have permanent restoration of their dental defects based on intraosseous implants. Evaluation of human allogeneic bone tissue grafts in reconstruction of atrophied alveolar ridge as a pre-implantation procedure. The material comprised 21 patients aged 19?63, treated between 2009 and 2012 by the same surgeon. Restoration of bone tissue defects...

  2. Ceacam1 separates graft-versus-host-disease from graft-versus-tumor activity after experimental allogeneic bone marrow transplantation.

    Directory of Open Access Journals (Sweden)

    Sydney X Lu

    Full Text Available Allogeneic bone marrow transplantation (allo-BMT is a potentially curative therapy for a variety of hematologic diseases, but benefits, including graft-versus-tumor (GVT activity are limited by graft-versus-host-disease (GVHD. Carcinoembryonic antigen related cell adhesion molecule 1 (Ceacam1 is a transmembrane glycoprotein found on epithelium, T cells, and many tumors. It regulates a variety of physiologic and pathological processes such as tumor biology, leukocyte activation, and energy homeostasis. Previous studies suggest that Ceacam1 negatively regulates inflammation in inflammatory bowel disease models.We studied Ceacam1 as a regulator of GVHD and GVT after allogeneic bone marrow transplantation (allo-BMT in mouse models. In vivo, Ceacam1(-/- T cells caused increased GVHD mortality and GVHD of the colon, and greater numbers of donor T cells were positive for activation markers (CD25(hi, CD62L(lo. Additionally, Ceacam1(-/- CD8 T cells had greater expression of the gut-trafficking integrin α(4β(7, though both CD4 and CD8 T cells were found increased numbers in the gut post-transplant. Ceacam1(-/- recipients also experienced increased GVHD mortality and GVHD of the colon, and alloreactive T cells displayed increased activation. Additionally, Ceacam1(-/- mice had increased mortality and decreased numbers of regenerating small intestinal crypts upon radiation exposure. Conversely, Ceacam1-overexpressing T cells caused attenuated target-organ and systemic GVHD, which correlated with decreased donor T cell numbers in target tissues, and mortality. Finally, graft-versus-tumor survival in a Ceacam1(+ lymphoma model was improved in animals receiving Ceacam1(-/- vs. control T cells.We conclude that Ceacam1 regulates T cell activation, GVHD target organ damage, and numbers of donor T cells in lymphoid organs and GVHD target tissues. In recipients of allo-BMT, Ceacam1 may also regulate tissue radiosensitivity. Because of its expression on both the

  3. Equine allogeneic bone marrow-derived mesenchymal stromal cells elicit antibody responses in vivo.

    Science.gov (United States)

    Pezzanite, Lynn M; Fortier, Lisa A; Antczak, Douglas F; Cassano, Jennifer M; Brosnahan, Margaret M; Miller, Donald; Schnabel, Lauren V

    2015-04-12

    This study tested the hypothesis that Major Histocompatibility Complex (MHC) incompatible equine mesenchymal stromal cells (MSCs) would induce cytotoxic antibodies to donor MHC antigens in recipient horses after intradermal injection. No studies to date have explored recipient antibody responses to allogeneic donor MSC transplantation in the horse. This information is critical because the horse is a valuable species for assessing the safety and efficacy of MSC treatment prior to human clinical application. Six MHC heterozygote horses were identified as non-ELA-A2 haplotype by microsatellite typing and used as allogeneic MHC-mismatched MSC recipients. MHC homozygote horses of known ELA-A2 haplotype were used as MSC and peripheral blood leukocyte (PBL) donors. One MHC homozygote horse of the ELA-A2 haplotype was the recipient of ELA-A2 donor MSCs as an MHC-matched control. Donor MSCs, which were previously isolated and immunophenotyped, were thawed and culture expanded to achieve between 30x10(6) and 50x10(6) cells for intradermal injection into the recipient's neck. Recipient serum was collected and tested for the presence of anti-donor antibodies prior to MSC injection and every 7 days after MSC injection for the duration of the 8-week study using the standard two-stage lymphocyte microcytotoxicity dye-exclusion test. In addition to anti-ELA-A2 antibodies, recipient serum was examined for the presence of cross-reactive antibodies including anti-ELA-A3 and anti-RBC antibodies. All MHC-mismatched recipient horses produced anti-ELA-A2 antibodies following injection of ELA-A2 MSCs and developed a wheal at the injection site that persisted for the duration of the experiment. Anti-ELA-A2 antibody responses were varied both in terms of strength and timing. Four recipient horses had high-titered anti-ELA-A2 antibody responses resulting in greater than 80% donor PBL death in the microcytotoxicity assays and one of these horses also developed antibodies that cross

  4. Allogeneic Compact Bone-Derived Mesenchymal Stem Cell Transplantation Attenuates the Severity of Idiopathic Pneumonia Syndrome in a Murine Bone Marrow Transplantation Model

    Directory of Open Access Journals (Sweden)

    Shu-kai Qiao

    2016-12-01

    Full Text Available Background/Aims: Idiopathic pneumonia syndrome (IPS is a serious and life-threatening lung complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT and currently no effective therapies exist. This study was designed to determine whether transplantation of allogeneic murine compact bone derived- mesenchymal stem cells (CB-MSCs could prevent the development of IPS. Methods: We tested the effects of CB-MSCs transplantation on IPS using an established murine model of C57BL/6 (H-2b→BALB/c (H-2d. Survival rates, body weight change, clinical GVHD scores, lung histological changes were assessed after IPS induction. Mechanistically, concentrations of cytokines (TNF-α, IFN-γ and IL-4 and chemokines (CCL5, CXCL9 and CXCL10 in bronchoalveolar lavage fluid (BALF from the recipient mice were measured at different time point post-transplantation. CD4+CD25+Foxp3+ regulatory T cell (Treg percentage, CCR5, CXCR3 and CCR7 expression on CD3+ T cells, and lung CXCR3, CCR5, CCR7, T-bet and GATA-3 mRNA levels were also evaluated at different time point post-transplantation. Results: Co-transplantation of CB-MSCs significantly attenuated the severity of lung injuries and increased survival rate of mice compared to non-cotransplanted mice. A higher Treg percentage, reduction of TNF-α, IFN-γ, CCL5, CXCL9 and CXCL10 levels, down-regulation of CXCR3 and CCR5, as well as up-regulation of CCR7, were observed in MSCs co-transplantation mice. Also, the prophylactic effect of CB-MSCs was associated with a shift of Th1/Th2 balance toward anti-inflammatory Th2 polarization. Conclusions: Allogeneic CB-MSCs effectively controlled the occurrence of IPS due to its profound immunomodulatory capacity. This may offer a novel prophylactic approach for IPS after allo-HSCT.

  5. Successful treatment with low-dose nivolumab in refractory Hodgkin lymphoma after allogeneic stem cell transplantation.

    Science.gov (United States)

    Onizuka, Makoto; Kojima, Minoru; Matsui, Keiko; Machida, Shinichiro; Toyosaki, Masako; Aoyama, Yasuyuki; Kawai, Hidetsugu; Amaki, Jun; Hara, Ryujiro; Ichiki, Akifumi; Ogawa, Yoshiaki; Kawada, Hiroshi; Nakamura, Naoya; Ando, Kiyoshi

    2017-07-01

    Previous studies have reported that an antibody that blocks programmed cell death 1 (PD-1) has therapeutic activity in patients with refractory/relapsed Hodgkin lymphoma (HL). However, the safety and efficacy of these agents in the post-allogeneic stem cell transplantation (allo-SCT) setting are not well known. Here, we describe a patient who was diagnosed as classical HL and treated with five regimens of chemotherapies with autologous SCT. Complete remission (CR) was not achieved following this initial treatment, so we performed allo-SCT from an HLA-matched sibling donor. Since his disease progressed at day 403 after allo-SCT, we decided to use nivolumab in the treatment of his refractory disease. To prevent the worsening of his chronic graft-versus-host disease (GVHD), we reduced the initial dose and frequency of nivolumab compared with the previous report. After four courses of 0.5 mg/kg of nivolumab every three weeks, FDG-PET imaging showed partial response (PR) to the treatment, a remarkable result. However, since the escalated dose of 2 mg/kg resulted in worsening of dyspnea and skin sclerosis, we initiated systemic administration of prednisolone and reduced nivolumab to 1 mg/kg. At the time of this report, his HL is in stable PR with three weekly administration of nivolumab and steroid controlled mild chronic GVHD.

  6. Effects of allogeneic bone marrow derived mesenchymal stromal cell therapy on voiding function in a rat model of Parkinson disease.

    Science.gov (United States)

    Campeau, Lysanne; Soler, Roberto; Sittadjody, Sivanandane; Pareta, Rajesh; Nomiya, Masanori; Zarifpour, Mona; Opara, Emmanuel C; Yoo, James J; Andersson, Karl-Erik

    2014-03-01

    Cellular therapy induced transient urodynamic improvement in a rat model of Parkinson disease in which bladder dysfunction was noted after unilateral injection of 6-hydroxydopamine into the medial forebrain bundle. We sought to prolong the effect by injecting allogeneic rat bone marrow mesenchymal stromal cells before and after microencapsulation into the substantia nigra pars compacta. Female rats underwent unilateral stereotactic injection of 6-hydroxydopamine in the medial forebrain bundle. Injection was performed in the ipsilateral substantia nigra pars compacta using vehicle alone or vehicle with nonmicroencapsulated or microencapsulated rat bone marrow derived mesenchymal stromal cells. Rats were evaluated by cystometry 7, 14, 28 and 42 days after treatment. Brains were extracted for immunostaining. At 42 days the nonmicroencapsulated group had lower threshold and intermicturition pressure, spontaneous activity and AUC than vehicle treated animals. Rats that received microencapsulated cells had lower threshold pressure at 28 days and lower spontaneous activity at 42 days than vehicle treated rats. Microencapsulated and nonmicroencapsulated rat bone marrow derived mesenchymal stromal cells were noted in the substantia nigra pars compacta up to 42 days after transplantation. At 42 days tyrosine hydroxylase positive neurons were more numerous in the substantia nigra pars compacta of the nonmicroencapsulated group, followed by the microencapsulated and vehicle treated groups. Urodynamic effects of the 6-hydroxydopamine lesion persisted up to 42 days after vehicle injection. Transplantation of nonmicroencapsulated rat bone marrow derived mesenchymal stromal cells improved urodynamic pressure by 42 days after treatment more markedly than microencapsulated cells. This was associated with more tyrosine hydroxylase positive neurons in the treated substantia nigra pars compacta of the nonmicroencapsulated group, suggesting that functional improvement requires a

  7. Treatment of Severely Resorbed Maxilla Due to Peri-Implantitis by Guided Bone Regeneration Using a Customized Allogenic Bone Block: A Case Report.

    Science.gov (United States)

    Blume, Oliver; Hoffmann, Lisa; Donkiewicz, Phil; Wenisch, Sabine; Back, Michael; Franke, Jörg; Schnettler, Reinhard; Barbeck, Mike

    2017-10-21

    The objective of this case report is to introduce a customized CAD/CAM freeze-dried bone allograft (FDBA) block for its use in Guided Bone Regeneration (GBR) procedures for severely deficient maxillary bones. Additionally, a special newly developed remote incision technique is presented to avoid wound dehiscence. The results show optimal integration behavior of the FDBA block after six months and the formation of new vital bone. Thus, the results of the present case report confirm the use of the customized CAD/CAM bone block for augmentation of complex defects in the maxillary aesthetic zone as a successful treatment concept.

  8. Treatment of Severely Resorbed Maxilla Due to Peri-Implantitis by Guided Bone Regeneration Using a Customized Allogenic Bone Block: A Case Report

    Directory of Open Access Journals (Sweden)

    Oliver Blume

    2017-10-01

    Full Text Available The objective of this case report is to introduce a customized CAD/CAM freeze-dried bone allograft (FDBA block for its use in Guided Bone Regeneration (GBR procedures for severely deficient maxillary bones. Additionally, a special newly developed remote incision technique is presented to avoid wound dehiscence. The results show optimal integration behavior of the FDBA block after six months and the formation of new vital bone. Thus, the results of the present case report confirm the use of the customized CAD/CAM bone block for augmentation of complex defects in the maxillary aesthetic zone as a successful treatment concept.

  9. Predictors for successful PBSC collection on the fourth day of G-CSF-induced mobilization in allogeneic stem cell donors.

    Science.gov (United States)

    van Oostrum, Anja; Zwaginga, Jaap Jan; Croockewit, Sandra; Overdevest, Jacqueline; Fechter, Mirjam; Ruiterkamp, Bart; Brand, Anneke; Netelenbos, Tanja

    2017-12-01

    Peripheral blood stem cells (PBSCs) used for allogeneic transplantation are collected by apheresis after pre-treatment of donors with G-CSF. Using modern apheresis devices stem cells can be collected more efficiently. It was studied whether collection on the 4th instead of the 5th day after initiation of G-CSF treatment might be feasible. Stem cell yields that could have been collected on day 4 were calculated in two cohorts treated with 10 µg/kg G-CSF once daily (n = 106, cohort I) or 5 µg/kg twice daily schedule (n = 85, cohort II). Harvests were predicted using the median collection efficiency (CE) of the apheresis machine and regarded successful when > 5.0 x106 CD34+/ kg recipient body weight. Successful harvests at day 4 could have been obtained in only 22.6% and 41.2% of donors in cohort I and II respectively, while the expected successful collections on day 5 were 55.7% and 76.5%. Individual donor factors that correlated with a successful harvest on day 4 were weight, BMI, age, ratio donor/recipient weight and total G-CSF dose in cohort I, whereas ratio donor/recipient weight was the only significant predictor in cohort II. Donor weight, BMI and total G-CSF dose correlated positively with CD34+ values in the blood on day 4 in all donors. However, donor characteristics were not able to be used as strong predictors in daily practice. In conclusion, PBSC collection on day 4 will not result in a successful harvest in most stem cell donors, however using a twice daily G-CSF scheme increases the yield. © 2017 Wiley Periodicals, Inc.

  10. Marrow damage and hematopoietic recovery following allogeneic bone marrow transplantation for acute leukemias: effect of radiation dose and conditioning regimen

    Science.gov (United States)

    Wilke, Christopher; Holtan, Shernan G.; Sharkey, Leslie; DeFor, Todd; Arora, Mukta; Premakanthan, Priya; Yohe, Sophia; Vagge, Stefano; Zhou, Daohong; Chakrabarty, Jennifer L. Holter; Mahe, Marc; Corvo, Renzo; Dusenbery, Kathryn; Storme, Guy; Weisdorf, Daniel J.; Verneris, Michael R.; Hui, Susanta

    2015-01-01

    Background and Purpose Total body irradiation (TBI) is a common component of hematopoietic cell transplantation (HCT) conditioning regimens. Preclinical studies suggest prolonged bone marrow (BM) injury after TBI could contribute to impaired engraftment and poor hematopoietic function. Materials and Methods We studied the longitudinal changes in the marrow environment in patients receiving allogeneic HCT with myeloablative (MA, n=42) and reduced intensity (RIC, n=56) doses of TBI from 2003-2013, including BM cellularity, histologic features of injury and repair, hematologic and immunologic recovery. Results Following MA conditioning, a 30% decrease in the marrow cellularity persisted at 1 year post-transplant (p=0.03). RIC HCT marrow cellularity transiently decreased but returned to baseline by 6 months even though the RIC group received mostly umbilical cord blood (UCB) grafts (82%, vs. 17% in the MA cohort, pmarrow vascular damage or inflammation. Recipients of more intensive conditioning did not show more persistent cytopenias with the exception of a tendency for minimal thrombocytopenia. Immune recovery was similar between MA and RIC. Conclusions These findings suggest that TBI associated with MA conditioning leads to prolonged reductions in marrow cellularity, but does not show additional histological evidence of long-term injury, which is further supported by similar peripheral counts and immunologic recovery. PMID:26653357

  11. Presence of donor-derived thymic epithelial cells in [B6-->MRL/lpr] mice after allogeneic intra-bone marrow-bone marrow transplantation (IBM-BMT).

    Science.gov (United States)

    Takaki, Takashi; Hosaka, Naoki; Miyake, Takashi; Cui, Wenhao; Nishida, Teruhisa; Inaba, Muneo; Ikehara, Susumu

    2008-12-01

    We have previously shown that allogeneic intra-bone marrow-bone marrow transplantation (IBM-BMT) can be used to treat autoimmune diseases in MRL/lpr (H-2(K)) mice with replacing not only hematolymphoid cells but also stromal cells by normal C57BL/6 (B6: H-2(b)) mouse cells. In the present study, we examined for existence of donor-derived thymic epithelial cells (TECs) in the host thymus using green fluorescent protein (GFP)-B6 (H-2(b)) mice. In [GFP-B6-->MRL/lpr] chimeric mice, splenocytes and thymocytes were completely replaced by donor-type cells, and levels of serum autoantibodies and proteinuria were significantly - reduced to those levels of normal donors. Interestingly, GFP-expressing TECs - not only medullary TECs, which express mouse thymus stromal (MTS)-10, but also cortical TECs, which express cytokeratin 18 - were found. Also, the number of autoimmune regulator (AIRE) expressing TECs, which regulates tissue-specific antigens to delete autoreactive cells, was reduced in the chimeric mice to that of the donor, whereas the number of forkhead box N1 (FOXN1) expressing TECs, which are crucial in the terminal differentiation of TECs, remained unchanged. These findings suggest that BMCs contain the precursors of functional TECs, and that they can differentiate into TECs, thereby correcting thymic function.

  12. Application of allogeneic bone marrow cells in view of residual alloreactivity: sirolimus but not cyclosporine evolves tolerogenic properties.

    Directory of Open Access Journals (Sweden)

    Kai Timrott

    Full Text Available Application of bone marrow cells (BMC is a promising strategy for tolerance induction, but usually requires strong depletion of the host immune system. This study evaluates the ability of immunosuppressants to evolve tolerogenic properties of BMC in view of residual alloreactivity.The rat model used a major histocompatibility complex (MHC class II disparate bone marrow transplantation (BMT setting (LEW.1AR1 (RT1auu → LEW.1AR2 (RT1aau. Heart grafts (LEW.1WR1 (RT1uua were disparate for the complete MHC to recipients and for MHC class I to BMC donors. Limited conditioning was performed by total body irradiation of 6 Gy. Cyclosporine (CsA or Sirolimus (Srl were administered for 14 or 28 days. Transplantation of heart grafts (HTx was performed at day 16 or at day 100 after BMT. Chimerism and changes in the T cell pool were detected by flow cytometry.Mixed chimeras accepted HTx indefinitely, although the composition of the regenerated T cell pool was not changed to a basically donor MHC class II haplotype. Non-chimeric animals rejected HTx spontaneously. BMC recipients, who received HTx during T cell recovery at day 16, accepted HTx only after pre-treatment with Srl, although chimerism was lost. CsA pre-treatment led to accelerated HTx rejection as did isolated application of BMC.Srl evolves tolerogenic properties of allogeneic BMC to achieve indefinite acceptance of partly MHC disparate HTx despite residual alloreactivity and in particular loss of chimerism.

  13. Graft-derived anti-HPA-2b production after allogeneic bone-marrow transplantation

    DEFF Research Database (Denmark)

    Taaning, E; Jacobsen, N; Morling, N

    1994-01-01

    We report on a male who received a bone-marrow allograft from his HLA identical sister for acute myelogenous leukaemia. After transplantation, the patient suffered from refractoriness to the transfusions of HLA-matched platelets and a strong platelet-specific antibody, anti-HPA-2b, of IgG1 subclass...

  14. A case series of CAEBV of children and young adults treated with reduced-intensity conditioning and allogeneic bone marrow transplantation: a single-center study.

    Science.gov (United States)

    Watanabe, Yuko; Sasahara, Yoji; Satoh, Miki; Looi, Chung Yeng; Katayama, Saori; Suzuki, Tasuku; Suzuki, Nobu; Ouchi, Meri; Horino, Satoshi; Moriya, Kunihiko; Nanjyo, Yuka; Onuma, Masaei; Kitazawa, Hiroshi; Irie, Masahiro; Niizuma, Hidetaka; Uchiyama, Toru; Rikiishi, Takeshi; Kumaki, Satoru; Minegishi, Masayoshi; Wada, Taizo; Yachie, Akihiro; Tsuchiya, Shigeru; Kure, Shigeo

    2013-09-01

    Epstein-Barr virus (EBV)-infected T or NK cells cause chronic active EBV infection (CAEBV). Allogeneic hematopoietic stem cell transplantation (HSCT) is curative treatment for CAEBV patients. However, chemotherapy prior to HSCT and optimal conditioning regimen for allogeneic HSCT are still controversial. We retrospectively analyzed five patients with CAEBV treated with reduced-intensity conditioning (RIC) consisted of fludarabine, cyclophosphamide, and low-dose total-body irradiation followed by allogeneic bone marrow transplantation in a single institute. Only one of five patients received chemotherapy prior to transplantation. We analyzed EBV-infected cells in a patient whose EBV load increased after HSCT by T-cell repertoire assay, separation of T-cell subpopulations, in situ hybridization and microsatellite analysis. All five patients achieved engraftment, complete chimera, and eradication of EBV load. All patients have been alive without any serious regimen-related toxicity for more than 16 months following HSCT. However, one patient transplanted from HLA-matched sibling donor developed clonal proliferation of CD4+ Vβ3+ T cells caused by monoclonal EBV infection on day 99 after transplantation. Further analysis revealed that the CD4+ Vβ3+ T cells selectively harbored EBV genome, and these infected cells were derived from donor T cells. Allogeneic HSCT with RIC is a safe and effective treatment for better overall survival and less regimen-related toxicity in patients with CAEBV. Our first pediatric case reported in the literature suggests that we should consider the possibility of persistent EBV infection in donor T cells as well as the relapse in recipient cells if EBV load increases after allogeneic HSCT. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Successful Treatment of Sinusitis by Acanthamoeba in a Pediatric Patient After Allogeneic Stem Cell Transplantation.

    Science.gov (United States)

    Juan, Antonio; Alonso, Laura; Olivé, Teresa; Navarro, Alexandra; Sulleiro, Elena; Sánchez de Toledo, José; Díaz de Heredia, Cristina

    2016-12-01

    Acanthamoeba infections are rare and mostly occur in immunocompromised patients. Most of the reported cases after stem cell transplantation have been diagnosed postmortem. We present the case of a 3-year-old boy with chronic graft versus host disease post hematopoietic transplantation, who was successfully treated for Acanthamoeba.

  16. Experimental study of the effect of autologous platelet-rich plasma on the early phases of osteoinduction by allogenic demineralized bone matrix.

    Science.gov (United States)

    Leventis, Minas D; Eleftheriadis, Efstathios; Oikonomopoulou, Panagiota; Vavouraki, Helen; Khaldi, Lubna; Tosios, Konstantinos I; Vardas, Emmanouil; Valavanis, Konstantinos D; Dontas, Ismene

    2012-10-01

    To evaluate the effect of autologous platelet-rich plasma (PRP) on the early phases of osteoinduction by allogenic demineralized bone matrix (DBM) in rabbit intramuscular positions. Allogenic DBM was produced from bones of 3 healthy rabbits. In each of 6 experimental animals, 0.3 mL autologous PRP was prepared and 2 muscle pouches were created, where 250 mg DBM + PRP (experimental sites) and 250 mg DBM without PRP (control sites) were randomly implanted. Animals were euthanized 3 weeks postoperatively. Histologic examination revealed uneventful healing in all cases, whereas remineralization of the periphery of the bone graft particles was a constant finding. In both control and experimental sites, fibroblasts and other mesenchymal cells (probably osteoprogenitor cells and preosteoblasts) were observed. The main histological difference was the recolonization of the empty lacunae of the bone graft particles by osteocytes at the control sites. The degradation of the graft at the control sites was statistically significantly quicker, although a statistically significant difference regarding the amount of the newly formed fibrous connective tissue was not observed. The present study demonstrated that in this experimental model, the addition of PRP to DBM had a negative effect on the early phases of osteoinduction at 3 weeks of observation.

  17. Reduced graft-versus-host disease-inducing capacity of T cells after activation, culturing, and magnetic cell sorting selection in an allogeneic bone marrow transplantation model in rats

    NARCIS (Netherlands)

    Weijtens, M; van Spronsen, A; Hagenbeek, A; Braakman, E; Martens, A

    Graft-versus-host disease (GvHD), a major complication of allogeneic bone marrow transplantation, has been ascribed to mature T cells in the graft. Because T cells play an important role in engraftment of the bone marrow and decrease the probability of relapse of leukemia, a treatment strategy was

  18. Nonunion of the femur treated with conventional osteosynthesis combined with autogenous and strut allogeneic bone grafts.

    Science.gov (United States)

    Weng, Lin-Hsiu; Wang, Jun-Wen

    2004-04-01

    In this study, we reviewed the results of conventional osteosynthesis combined with strut onlay allografts and autogenous bone grafts as the treatment for nonunion of the femur. We conducted a retrospective study of 18 patients with nonunion of the femur treated with internal fixation (eight 95 degree fixed-angled blade plates, 7 intramedullary nails, 2 dynamic hip compression plates and screws, and 1 condylar buttress plate) and autogenous bone grafts and cortical strut allografts. There were 1.8 operations on average before surgery. The average time from the initial treatment of the fracture or osteotomy to surgery was 32.5 months. The average follow-up was 32.2 months. All 18 nonunions had healed by the time of follow-up. Positive intraoperative cultures (Staphylococcus epidermidis) in 2 patients were resolved by parenteral antibiotics with no additional treatment. Removal of implants was required in 5 patients because of screw irritation or bony union. One concomitant quadricepsplasty as well as 2 excisions of a protruding graft were required because of restricted knee motion or impingement. For difficult nonunions of the femur in the current study, strict adherence to the principles of the treatment of nonunion and the addition of strut allografts to enhance stability and repair potential proved to be a good alternative.

  19. Validation of the sterilization procedure of allogeneic avital bone transplants using peracetic acid-ethanol.

    Science.gov (United States)

    Pruss, A; Baumann, B; Seibold, M; Kao, M; Tintelnot, K; von Versen, R; Radtke, H; Dörner, T; Pauli, G; Göbel, U B

    2001-06-01

    Different procedures are available to inactivate bacteria and fungi, including their spores, as well as viruses in human bone transplants. The most efficient methods are considered to be gamma irradiation and thermal inactivation as well as chemical sterilization methods like the peracetic acid-ethanol treatment (PES). Following national and international standards or draft standards, the antimicrobial effectiveness of this procedure was evaluated. Due to the standardizable size as well as the clinical relevance, defatted human spongiosa cuboids (15x15x15 mm) served as model system. After treatment with PES for 2 and 4 hours, respectively, the titre of living micro-organisms was determined in the supernatant and the cuboid. A reduction in the titre of viable micro-organisms below the detection level (reduction factor >5 log10) was already achieved after an incubation time of 2 hours (Staphylococcus aureus, Enterococcus faecium, Pseudomonas aeruginosa, Bacillus subtilis, Clostridium sporogenes, Mycobacterium terrae, Candida albicans as well as spores of Bacillus subtilis). No viable micro-organisms could be detected in any of the PES-treated test cuboids. Spores of Aspergillus niger were also completely inactivated. The PES procedure proved to be a reliable method for the sterilization of human bone transplants derived from spongiosa. Copyright 2001 The International Association for Biologicals.

  20. Allogeneic split-skin grafting in stem cell transplanted patients

    DEFF Research Database (Denmark)

    Olsen, Jan Kyrre Berg; Vindeløv, Lars; Schmidt, G.

    2008-01-01

    SUMMARY: We present a unique case of a bone marrow stem cell transplanted (BMT) patient with cutaneous chronic Graft versus Host Disease (cGvHD) who underwent successful allogeneic split-thickness skin graft (STSG) transplantation. BMT had previously been carried out due to myelodysplasia and non......). Allogeneic skin grafts are known to be acutely rejected. Successful allogeneic STSG has only been reported in sporadic cases of identical twins (isotransplantation). This case is the first to demonstrate what works in theory: the immune system of a stem cell transplanted patient with 100% or mixed stable...... donor chimaerism will not recognise skin from the stem cell donor as foreign. Due to advances in haematology, the number of BMT patients and their long-term survival is expected to increase. cGvHD, predisposing to skin problems and ulcerations, complicates up to 70% of cases of BMT. In BMT patients...

  1. Ex Vivo Oncolytic Virotherapy with Myxoma Virus Arms Multiple Allogeneic Bone Marrow Transplant Leukocytes to Enhance Graft versus Tumor.

    Science.gov (United States)

    Lilly, Cameron L; Villa, Nancy Y; Lemos de Matos, Ana; Ali, Haider M; Dhillon, Jess-Karan S; Hofland, Tom; Rahman, Masmudur M; Chan, Winnie; Bogen, Bjarne; Cogle, Christopher; McFadden, Grant

    2017-03-17

    Allogeneic stem cell transplant-derived T cells have the potential to seek and eliminate sites of residual cancer that escaped primary therapy. Oncolytic myxoma virus (MYXV) exhibits potent anti-cancer efficacy against human cancers like multiple myeloma (MM) and can arm transplant-derived T cells to become more effective cancer killers in vitro and in an immunodeficient xenotransplant murine model. Here, we tested ex vivo MYXV virotherapy against residual murine MM in immunocompetent mice using an allogeneic mouse-mouse model. In contrast to all human MM cell lines previously tested, the murine MM cell line tested here was highly resistant to direct MYXV infection and oncolysis in vitro. Despite this in vitro resistance, we found that ex vivo MYXV-armed allogeneic bone marrow (BM) transplantation dramatically ablated pre-seeded residual MM in vivo. Unexpectedly, we show that both neutrophils and activated T cells from the donor function as virus-armed carrier cells, and MYXV-preloaded cells enhanced MM killing. Our results demonstrate a novel therapeutic paradigm for residual cancer, in which multiple classes of allotransplant leukocytes can be armed by MYXV ex vivo to enhance the graft-versus-tumor effects.

  2. Ex Vivo Oncolytic Virotherapy with Myxoma Virus Arms Multiple Allogeneic Bone Marrow Transplant Leukocytes to Enhance Graft versus Tumor

    Directory of Open Access Journals (Sweden)

    Cameron L. Lilly

    2017-03-01

    Full Text Available Allogeneic stem cell transplant-derived T cells have the potential to seek and eliminate sites of residual cancer that escaped primary therapy. Oncolytic myxoma virus (MYXV exhibits potent anti-cancer efficacy against human cancers like multiple myeloma (MM and can arm transplant-derived T cells to become more effective cancer killers in vitro and in an immunodeficient xenotransplant murine model. Here, we tested ex vivo MYXV virotherapy against residual murine MM in immunocompetent mice using an allogeneic mouse-mouse model. In contrast to all human MM cell lines previously tested, the murine MM cell line tested here was highly resistant to direct MYXV infection and oncolysis in vitro. Despite this in vitro resistance, we found that ex vivo MYXV-armed allogeneic bone marrow (BM transplantation dramatically ablated pre-seeded residual MM in vivo. Unexpectedly, we show that both neutrophils and activated T cells from the donor function as virus-armed carrier cells, and MYXV-preloaded cells enhanced MM killing. Our results demonstrate a novel therapeutic paradigm for residual cancer, in which multiple classes of allotransplant leukocytes can be armed by MYXV ex vivo to enhance the graft-versus-tumor effects.

  3. Studies of allogeneic bone marrow and spleen cell transplantation in a murine model using ultraviolet-B light

    Energy Technology Data Exchange (ETDEWEB)

    Pamphilon, D.H.; Alnaqdy, A.A.; Godwin, V.; Preece, A.W.; Wallington, T.B. (South Western Regional Transfusion Centre, Bristol (United Kingdom))

    1991-05-01

    Ultraviolet irradiation inhibits alloreactive and mitogen-induced responses and might reduce both graft-versus-host and host-versus-graft reactions after bone marrow transplantation (BMT). We have studied proliferative responses to mitogens and reactivity in mixed lymphocyte culture after irradiation with ultraviolet (UV)-B light using splenocytes from Balb/c (H-2d) and CBA (H-2k) mice. Response to mitogens and in MLC was strongly inhibited by 20 J/m{sup 2} and abolished at 50 J/m{sup 2}. Clonogenic cell recovery (CFU-GM; CFU-S) after UV-B irradiation was also reduced. When bone marrow and spleen cells were transplanted from parent (Balb/c) animals into F1 hybrid (Balb/c X CBA) recipients, all animals died with features indicative of graft-versus-host disease (GVHD) in 34 days. If the grafts were first irradiated with 100 J/m{sup 2} of UV-B at a mean wavelength of 310 nm, then 76% survived to day 80 when they were killed and shown to have normal marrow cellularity. The remainder died in marrow aplasia or of GVHD. H-2 typing in a group of surviving recipients showed either donor hematopoiesis only (8 of 15), mixed allogeneic chimerism (5 of 15), or recipient type hematopoiesis (2 of 15). Higher doses (200 to 300 J/m{sup 2}) were detrimental to survival with 88% of recipients dying in marrow aplasia. Syngeneic BMT in Balb/c mice showed slower hematopoietic reconstitution when the grafts were first irradiated with 100 J/m{sup 2}. After BMT from Balb/c to CBA mice all recipients of unirradiated grafts died within 54 days. By contrast, after graft irradiation with 100 J/m{sup 2} survival of recipient animals to day 80 was 59%. If these grafts were treated with 50 J/m{sup 2} survival was only 26% with an increase in deaths due to GVHD. Hematopoiesis at day 80 in a group of survivors studied by Ig heavy chain allotyping indicated donor type hematopoiesis in 6 of 10 (50 J/m{sup 2}) and 2 of 9 (100 J/m{sup 2}).

  4. Adhesion, proliferation and osteogenic differentiation of human MSCs cultured under perfusion with a marine oxygen carrier on an allogenic bone substitute.

    Science.gov (United States)

    Le Pape, Fiona; Richard, Gaëlle; Porchet, Emmanuelle; Sourice, Sophie; Dubrana, Frédéric; Férec, Claude; Polard, Valérie; Pace, Richard; Weiss, Pierre; Zal, Franck; Delépine, Pascal; Leize, Elisabeth

    2017-08-22

    Tissue engineering strategies have been developed to optimize osseointegration in dental implant surgery. One of the major problems is the non-homogeneous spatial cell distribution in the scaffold, as well as subsequent matrix production. Insufficient nutrient and oxygen supplies inside the scaffold are factors in this phenomenon. To mediate this gradient formation, we have implemented a perfusion culture method to seed human bone marrow mesenchymal stem cells (MSCs) into three-dimensional (3-D)-allogenic bone scaffolds in combination with a marine haemoglobin, HEMOXCell(®), for oxygen delivery. Cell culture was performed under static and perfusion conditions, with standard and osteogenic media, with and without HEMOXCell(®). The cell seeding efficiency, as well as MSC/scaffold cytocompatibly were assessed using viability and proliferation assays. Scaffolds' cellularization and extracellular matrix (ECM) formation were analyzed using scanning electron microscopy and histological staining. Cell differentiation was investigated with osteogenic biomarkers gene expression analysis. The perfusion culture was observed to significantly promote MSC proliferation and differentiation throughout the scaffolds, especially when using the induction medium w/HEMOXCell(®). Our data suggest that perfusion culture of MSC into allogenic bone substitute with HEMOXCell(®) as a natural oxygen carrier is promising for tissue engineering applications to oxygenate hypoxic areas and to promote cellular proliferation.

  5. Metabolic bone diseases in patients after allogeneic hematopoietic stem cell transplantation: report from the Consensus Conference on Clinical Practice in chronic graft-versus-host disease.

    Science.gov (United States)

    Hautmann, Anke Heidewig; Elad, Sharon; Lawitschka, Anita; Greinix, Hildegard; Bertz, Hartmut; Halter, Joerg; Faraci, Maura; Hofbauer, Lorenz Christian; Lee, Stephanie; Wolff, Daniel; Holler, Ernst

    2011-09-01

    With improved outcome of allogeneic stem cell transplantation (allo-SCT) for hematologic malignancies, long-term complications gain greater importance. Skeletal complications such as osteoporosis or avascular necrosis (AVN) occur frequently in allogeneic recipients with a cumulative incidence of diminished bone mineral density of 24-50% between 2 and 12 months after allo-SCT and a cumulative incidence of AVN in as many as 19% of patients 3 years after allo-SCT. Here, we present a review as part of the German, Austrian, and Swiss Consensus Conference on clinical practice in chronic graft-versus-host disease, held 2009 in Regensburg. The Consensus Conference aimed to achieve a consensus on the current evidence of diagnosis, prevention, and therapeutic options of late complications after allo-SCT summarizing and discussing the literature on these topics. In this report, we provide recommendations for metabolic bone diseases agreed upon by the working party. This includes guidelines for diagnosis, prevention, and therapeutic options in patients with low bone mass or AVN. © 2011 The Authors. Transplant International © 2011 European Society for Organ Transplantation.

  6. Evaluation of reactivation of HSV1, HHV6, CMV and EBV in a population of patients undergoing allogeneic bone marrow transplantation

    Directory of Open Access Journals (Sweden)

    Caterina Matinato

    2011-06-01

    Full Text Available Herpes viruses are recognized as important pathogens as a result of viral reactivation in immunocompromised hosts, especially in patients undergoing bone marrow transplantation. Objectives of this study were the assessment of the reactivation of herpes virus HSV1, HHV6, CMV and EBV and the correlation between viral reactivation and progression of transplantation in a population of patients undergoing allogeneic bone marrow transplantation at Fondazione IRCCS Ospedale Maggiore Ca’ Granda Policlinico, Milan. Viral DNA was detected and quantified by Real Time PCR in a population of 35 patients undergoing allogeneic bone marrow transplantation. The viral reactivation was observed in 7 patients for HSV1 (20%, 6 patients for HHV6 (17.1%, 11 patients for CMV (31.4% and 4 patients for EBV (11.4%. Difference in the incidence of aGVDH between patients with viral reactivation versus those for which there was no reactivation was statistically significant. These data confirm the importance of monitoring viral load for the management of antiviral therapy in order to prevent CMV disease and complications related to herpes viruses reactivation.

  7. Recurrence of chronic active Epstein-Barr virus infection from donor cells after achieving complete response through allogeneic bone marrow transplantation.

    Science.gov (United States)

    Arai, Ayako; Imadome, Ken-ichi; Wang, Ludan; Wu, Nan; Kurosu, Tetsuya; Wake, Atsushi; Yamamoto, Hisashi; Ota, Yasunori; Harigai, Masayoshi; Fujiwara, Shigeyoshi; Miura, Osamu

    2012-01-01

    We report the case of a 35-year-old woman with chronic active Epstein-Barr virus (EBV) infection (CAEBV). She underwent allogeneic bone marrow transplantation (BMT) from an unrelated male donor and achieved a complete response. However, her CAEBV relapsed one year after BMT. EBV-infected cells proliferated clonally and revealed a 46XY karyotype. In addition, the infecting EBV strain differed from that detected before BMT. These findings indicated that her disease had developed from donor cells. This is the first report of donor cell-derived CAEBV that recurred after transplantation, suggesting that host factors may be responsible for the development of this disease.

  8. Changes in cell and protein content of cerebrospinal fluid in children with acute lymphoblastic leukaemia after allogeneic bone marrow transplantation

    NARCIS (Netherlands)

    van den Berg, H.; Gerritsen, E. J.; Haraldsson, A.; Vossen, J. M.

    1993-01-01

    The material from 59 and 134 cerebrospinal fluid (CSF) samples, taken in the week prior to grafting and during the first 100 days after grafting respectively, were examined from 37 children undergoing allogeneic BMT. All CSF samples were obtained from lumbar punctures performed for regular

  9. Allogeneic bone marrow transplantation with T cell-depleted partially matched related donors for advanced acute lymphoblastic leukemia in children and adults: a comparative matched cohort study.

    Science.gov (United States)

    Fleming, D R; Henslee-Downey, P J; Romond, E H; Harder, E J; Marciniak, E; Munn, R K; Messino, M J; Macdonald, J S; Bishop, M; Rayens, M K; Thompson, J S; Foon, K A

    1996-06-01

    Allogeneic BMT provides the best treatment currently available for long-term disease-free survival in patients with recurrent ALL. Historically, partially matched related donors provided the opportunity for treatment to a greater number of patients than matched related donors at the expense of decreased overall survival. In this study we compare the results in recurrent ALL patients transplanted with either HLA identical sibling bone marrow or partially matched related bone marrow. Thirty-two patients with relapsed ALL received partially matched bone marrows from a relative with one to three HLA, A, B and Dr antigen mismatches. Bone marrow was partially T cell-depleted with murine T10B9.1A-31 moAb. Sixteen patients with relapsed ALL received HLA-matched sibling bone marrows. All partially matched patients received additional GVHD prophylaxis with methylprednisolone in addition to anti-CD5 immunotoxin and/or CYA. All matched patients in addition to methylprednisolone received MTX and/or CYA. We observed no difference in disease-free survival between patients transplanted with partially matched bone marrow (median follow-up 1252 days, range 778-2035 days) vs those transplanted with HLA-matched bone marrow (median follow-up 1472 days, range 1165-2800 days; P = 0.48). Median survival for all patients is 38% (95% CI 24-52%) at 6 years. Patients transplanted in remission had a significant increase in disease-free survival when compared to those in relapse (P = 0.007). Our data suggest that partially matched BMTs from related donors are a comparable alternative to fully matched transplants in patients with ALL.

  10. Clinical effectiveness of hyperbaric oxygen therapy for BK-virus-associated hemorrhagic cystitis after allogeneic bone marrow transplantation.

    Science.gov (United States)

    Savva-Bordalo, J; Pinho Vaz, C; Sousa, M; Branca, R; Campilho, F; Resende, R; Baldaque, I; Camacho, O; Campos, A

    2012-08-01

    Late-onset hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (HSCT) has been associated with BK virus (BKV). Antiviral drugs are of limited efficacy and the optimal treatment for HC has not yet been established. Hyperbaric oxygen (HBO) may benefit these patients. We, therefore, retrospectively evaluated the effectiveness of HBO therapy in 16 patients with HC after allogeneic HSCT. All 16 patients had macroscopic hematuria and BKV infection. Patients received 100% oxygen in a hyperbaric chamber at 2.1 atmospheres for 90 min, 5 days per week, with a median 13 treatments (range, 4-84). Fifteen patients (94%) showed complete resolution of hematuria. Median urinary DNA BKV titers declined after HBO (P<0.05). Patients started on HBO earlier after diagnosis of HC responded sooner (P<0.05). HBO was generally well tolerated and proved to be a reliable option for this difficult to manage condition.

  11. Feasibility and Efficiency of Human Bone Marrow Stromal Cell Culture with Allogeneic Platelet Lysate-Supplementation for Cell Therapy against Stroke

    Directory of Open Access Journals (Sweden)

    Chengbo Tan

    2016-01-01

    Full Text Available Currently, there is increasing interest in human bone marrow stromal cells (hBMSCs as regeneration therapy against cerebral stroke. The aim of the present study was to evaluate the feasibility and validity of hBMSC cultures with allogeneic platelet lysates (PLs. Platelet concentrates (PC were harvested from healthy volunteers and made into single donor-derived PL (sPL. The PL mixtures (mPL were made from three different sPL. Some growth factors and platelet cell surface antigens were detected by enzyme-linked immunosorbent assay (ELISA. The hBMSCs cultured with 10% PL were analyzed for their proliferative potential, surface markers, and karyotypes. The cells were incubated with superparamagnetic iron oxide (SPIO agents and injected into a pig brain. MRI and histological analysis were performed. Consequently, nine lots of sPL and three mPL were prepared. ELISA analysis showed that PL contained adequate growth factors and a particle of platelet surface antigens. Cell proliferation capacity of PLs was equivalent to or higher than that of fetal calf serum (FCS. No contradiction in cell surface markers and no chromosomal aberrations were found. The MRI detected the distribution of SPIO-labeled hBMSCs in the pig brain. In summary, the hBMSCs cultured with allogeneic PL are suitable for cell therapy against stroke.

  12. BK polyomavirus-associated hemorrhagic cystitis among pediatric allogeneic bone marrow transplant recipients: treatment response and evidence for nosocomial transmission.

    Science.gov (United States)

    Koskenvuo, Minna; Dumoulin, Alexis; Lautenschlager, Irmeli; Auvinen, Eeva; Mannonen, Laura; Anttila, Veli-Jukka; Jahnukainen, Kirsi; Saarinen-Pihkala, Ulla M; Hirsch, Hans H

    2013-01-01

    BK polyomavirus-associated hemorrhagic cystitis (BK-PyVHC) is a significant complication of allogenic hematopoietic stem cell transplantation (HSCT), but risk factors and treatment are currently unresolved. BK-PyVHC typically presents with clinical cystitis, macrohematuria, and increasing urine and blood BKV loads. Characterization of children undergoing allogeneic HSCT with BK-PyVHC and their clinical and antibody response to cidofovir treatment. By prospective screening of urine and plasma in 50 pediatric allogenic HSCT performed between 2008 and 2010, we identified 6 (12%) children with BK-PyVHC. Cidofovir was administered intravenously to 5 patients and intravesically to 4 patients (3 double treatments). Decreasing BKV viremia of>2log(10)copies/mL and clinical resolution was seen in 4 patients over 5-12 weeks. Responses occurred only in patients mounting BKV-specific IgM and IgG responses. Epidemic curve plots, BKV genotyping and contact tracing provided evidence of transmission between 2 BKV-seronegative patients, but ruled out transmission among the remaining four patients The data suggest that BK-PyVHC may be the result of nosocomial transmission in children with low/undetectable BKV antibodies and raises urgent questions about appropriate infection control measures and the role of cidofovir. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Chronic active Epstein-Barr virus infection with marked pericardial effusion successfully treated with allogeneic peripheral blood stem cell transplantation.

    Science.gov (United States)

    Matsui, Shinichiro; Takeda, Yusuke; Isshiki, Yusuke; Yamazaki, Atsuko; Nakao, Sanshiro; Takaishi, Koji; Nagao, Yuhei; Hasegawa, Nagisa; Togasaki, Emi; Shimizu, Ryoh; Kawajiri, Chika; Sakai, Shio; Mimura, Naoya; Takeuchi, Masahiro; Ohwada, Chikako; Sakaida, Emiko; Iseki, Tohru; Imadome, Ken-Ichi; Nakaseko, Chiaki

    2016-05-01

    A 23-year-old woman presented with a persistent fever and shortness of breath. Computed tomography showed marked pericardial effusion, hepatosplenomegaly, and cervical and mediastinal lymph node swelling. Epstein-Barr virus (EBV) antibody titers were abnormally elevated, and the copy number of EBV-DNA was increased in peripheral blood. Based on these observations, she was diagnosed with chronic active EBV infection (CAEBV). The EBV-infected cells in her peripheral blood were CD4(+)T lymphocytes. Fever and pericardial effusion improved following treatment with a combination of prednisolone, etoposide, and cyclosporine; however, peripheral blood EBV-DNA levels remained high. The patient underwent allogeneic peripheral blood stem cell transplantation from an EBV-seronegative, HLA-matched sibling donor, with fludarabine and melphalan conditioning. The post-transplantation course was uneventful, except for mild skin acute graft-versus-host disease (grade 2). EBV-DNA became undetectable in peripheral blood 98 days post transplantation. She has since been in good health without disease recurrence. CAEBV is a potentially fatal disease caused by persistent EBV infection of T lymphocytes or natural killer cells, thus requiring prompt treatment and allogeneic transplantation. Pericardial effusion is rarely observed in CAEBV and can impede its diagnosis. Therefore, we should be aware that patients may present with marked pericardial effusion as an initial manifestation of CAEBV.

  14. Successful nonsibling bone marrow transplantation in severe combined immunodeficiency

    DEFF Research Database (Denmark)

    Ramsøe, K; Skinhøj, P; Andersen, V

    1978-01-01

    Severe combined immunodeficiency (SCID) was diagnosed in a girl immediately after birth; her older brother had SCID and was successfully reconstituted by bone marrow transplantation from his uncle. She was isolated in a laminar air flow bench and decontaminated. The father differed by one HLA-A a......A); tests of cell-mediated immunity are normal. Apart from slight upper respiratory infections, the patient has been healthy. Physical and psychological development have been normal....

  15. [The role of third-party tolerogenic dendritic cells in the prevention of acute graft-versus-host-disease following allogeneic bone marrow transplantation in mice].

    Science.gov (United States)

    Li, Gui-ping; Yang, Jie; Hao, Jun; Yang, Yi-ming; Ren, Ya-na; Xie, Ru-feng; Fan, Hua-hua; Qian, Kai-cheng

    2012-06-01

    To explore the biological characteristic of third-party-derived tolerogenic DC(tDC) and the influence of third-party-derived tDC on acute graft-versus-host-disease (aGVHD) following allogeneic bone marrow transplantation (allo-BMT) in mice. tDC from bone marrow cells of D1 mice was cultured with low doses of GM-CSF, IL-10 and TGF-β1D1. The phenotype, expression of cytokines and function associated molecules were identified with FACS and RT-PCR. Mixed lymphocyte reaction was applied to analyze the influence of third-party-derived tDC on allo-CD4(+)T cells proliferation in vitro. Different doses of D1-tDC were adoptive transferred in the aGVHD model in allogeneic BMT which B6 mice as donors and D2 mice as recipients. Survival time, clinical GVHD score and the levels of Th1/2 cytokines in serum were monitored after allo-BMT using the aGVHD model as control. tDC expressed lower levels of MHC II and co-stimulatory molecules, such as CD80, CD86 and CD40, even when stimulated by LPS. The results by RT-PCR indicated that tDC expressed low levels of IL-12p40 and high levels of immunosuppressive molecules, such as IL-10, TGF-β, Fas Ligand, indoleamine 2, 3-dioxygenase (IDO) and arginase. In the allogeneic MLR, third-party tDC suppressed allo-CD4(+)T cells proliferation, which was relative to the dose of tDC. In the B6→D2 mouse model, all aGVHD mice died within 18 days. Remarkably, if 10(4) third-party tDC were transferred, 60% mice survived at least 60 days. When the doses of tDC were reduced to 10(3) cells, only 20% of mice survived day 60, and when increased tDC to 10(5), all of the mice died within day 37 after allo-BMT. The cytokine levels in serum indicated that 10(4) tDC-treated mice secreted in vivo high level of IL-10 21d after BMT (P party tDC could suppress allo-CD4(+)T cells proliferation in vitro and prevent aGVHD in allogeneic BMT mode, which may be mediated by modulating tolerogenic cytokines secretion, such as IL-10. And this effect was associated with the

  16. Transplante de medula óssea com doador familiar parcialmente compatível Partially matched family donor allogeneic bone marrow transplantation

    Directory of Open Access Journals (Sweden)

    Rosaura Saboya

    2010-05-01

    Full Text Available O transplante de células-tronco hematopoéticas alogênico (TCTH alo após um regime de condicionamento ablativo ou não mieloablativo é um tratamento potencialmente curativo para uma grande variedade de doenças malignas hematológicas e outras desordens não hematológicas. O doador HLA aparentado totalmente compatível continua contribuindo para as melhores taxas de sobrevida global e livre de progressão; contudo, apenas 25%-30% dos candidatos a TCTH alo apresentam um doador aparentado HLA (antígenos leucocitários humanos compatível. A busca por doadores não aparentados cadastrados nos bancos de medula óssea nacional e internacional demanda tempo, que, a depender da situação clínica da doença do paciente e sua deterioração clínica, não permite a espera. Neste sentido, o transplante com doadores familiares parcialmente compatíveis tem se mostrado uma opção terapêutica. Este artigo revisa a literatura e demonstra a factibilidade desta opção.Myeloablative or non-myeloablative related allogeneic bone marrow transplantation is a curative treatment in some oncologic and hematologic diseases. Unfortunately, only 25 to 30% of patients find a fully matched related donor. National and International donor programs are an option, however, much time is lost and patients can not wait because of their advance disease status or clinical deterioration. Partially matched family donor allogeneic bone marrow transplantation may be an option. This article reviews the literature on this subject.

  17. Cerebral toxoplasmosis in an adolescent post allogeneic hematopoietic stem cell transplantation: successful outcome by antiprotozoal chemotherapy and CD4+ T-lymphocyte recovery.

    Science.gov (United States)

    Kerl, K; Ehlert, K; Brentrup, A; Schiborr, M; Keyvani, K; Becker, K; Rossig, C; Groll, A H

    2015-02-01

    Toxoplasmosis is a rare opportunistic infection in pediatric allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients and associated with severe T-cell deficiency. Here, we report the successful management of cerebral toxoplasmosis in a 15-year-old adolescent 4 months post allo-HSCT for non-Hodgkin lymphoma through rapid invasive diagnostics, long-term antiprotozoal chemotherapy, and an hematopoietic stem cell boost for persistently poor graft function. While supportive care and antiprotozoal chemotherapy achieved stabilization, definite improvement only occurred following recovery of CD4(+) T lymphocytes to >100 cells/μL. At 5 years after the diagnosis of toxoplasmosis, the patient is in continuing remission with normalized clinical and imaging findings. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Allogeneic Bone Marrow Transplant from MRL/MpJ Super-Healer Mice Does Not Improve Articular Cartilage Repair in the C57Bl/6 Strain.

    Directory of Open Access Journals (Sweden)

    Catherine A Leonard

    Full Text Available Articular cartilage has been the focus of multiple strategies to improve its regenerative/ repair capacity. The Murphy Roths Large (MRL/MpJ "super-healer" mouse demonstrates an unusual enhanced regenerative capacity in many tissues and provides an opportunity to further study endogenous cartilage repair. The objective of this study was to test whether the super-healer phenotype could be transferred from MRL/MpJ to non-healer C57Bl/6 mice by allogeneic bone marrow transplant.The healing of 2mm ear punches and full thickness cartilage defects was measured 4 and 8 weeks after injury in control C57Bl/6 and MRL/MpJ "super-healer" mice, and in radiation chimeras reconstituted with bone marrow from the other mouse strain. Healing was assessed using ear hole diameter measurement, a 14 point histological scoring scale for the cartilage defect and an adapted version of the Osteoarthritis Research Society International scale for assessment of osteoarthritis in mouse knee joints.Normal and chimeric MRL mice showed significantly better healing of articular cartilage and ear wounds along with less severe signs of osteoarthritis after cartilage injury than the control strain. Contrary to our hypothesis, however, bone marrow transplant from MRL mice did not confer improved healing on the C57Bl/6 chimeras, either in regards to ear wound healing or cartilage repair.The elusive cellular basis for the MRL regenerative phenotype still requires additional study and may possibly be dependent on additional cell types external to the bone marrow.

  19. Dipeptidyl peptidase IV (DPPIV/CD26) inhibition does not improve engraftment of unfractionated syngeneic or allogeneic bone marrow after nonmyeloablative conditioning

    Science.gov (United States)

    Schwaiger, Elisabeth; Klaus, Christoph; Matheeussen, Veerle; Baranyi, Ulrike; Pilat, Nina; Ramsey, Haley; Korom, Stephan; De Meester, Ingrid; Wekerle, Thomas

    2012-01-01

    In order to develop minimally toxic bone marrow transplantation (BMT) protocols suitable for use in a wider range of indications, it is important to identify ways to enhance BM engraftment at a given level of recipient conditioning. CXCL12/stromal cell-derived factor-1α plays a crucial physiological role in homing of hematopoietic stem cells to BM. It is regulated by the ectopeptidase dipeptidyl peptidase IV (DPPIV; DPP4) known as CD26, which cleaves dipeptides from the N-terminus of polypeptide chains. Blocking DPPIV enzymatic activity had a beneficial effect on hematopoietic stem cell engraftment in various but very specific experimental settings. Here we investigated whether inhibition of DPPIV enzymatic activity through Diprotin A or sitagliptin (Januvia) improves BM engraftment in nonmyeloablative murine models of syngeneic (i.e., CD45-congenic) and allogeneic (i.e., Balb/c to B6) BMT (1 Gy total body irradiation, 10–15 × 106 unseparated BM cells/mouse). Neither Diprotin A administered in vivo at the time of BMT and/or used for in vitro pretreatment of BM nor sitagliptin administered in vivo had a detectable effect on the level of multilineage chimerism (follow-up >20 weeks). Similarly, sitagliptin did not enhance chimerism after allogeneic BMT, even though DPPIV enzymatic activity measured in serum was profoundly inhibited (>98% inhibition at peak exposure). Our results provide evidence that DPPIV inhibition via Diprotin A or sitagliptin does not improve engraftment of unseparated BM in a nonmyeloablative BMT setting. PMID:22085453

  20. Granulocytic Sarcoma by AML M4eo (inv16 after Allogeneic Stem Cell Transplantation without Bone Marrow Involvement

    Directory of Open Access Journals (Sweden)

    Stephan Zaenker

    2011-01-01

    Full Text Available Granulocytic sarcoma (GS represents a rare type of extramedullar manifestation from the acute myeloid leukaemia (AML. We report the case of a patient with recurrences of AML M4eo leukaemia in the uterus and the small intestine at 3 and 5 years, respectively, after matched related peripheral blood stem cell transplantation (PBSCT. The patient underwent the withdrawal of immunosuppression, hysterectomy, and local irradiation at first relapse, as well as systemic chemotherapy and donor lymphocyte infusions at second recurrence, inducing a second and third complete remission, respectively. At year six after transplantation, the patient experienced disease progression by meningeosis leukaemia to which she succumbed despite intrathecal chemotherapy. Following allogeneic stem cell transplantation, awareness for atypical manifestations of granulocytic sarcoma appears prudent, the cellular immunotherapy should aim at immunological disease control.

  1. Effect of allogeneic bone marrow derived stromal cells on induced third-degree skin burn healing in mouse

    Directory of Open Access Journals (Sweden)

    Leyla Soleymani

    2014-10-01

    Conclusion: This experimental modulation of wound healing suggests that bone marrow-derived stromal cells can significantly enhance the rate of wound healing possibly through stimulation of granulation tissue, angiogenesis, fibroblast proliferation and collagen deposition.

  2. Pathways analysis of differential gene expression induced by engrafting doses of total body irradiation for allogeneic bone marrow transplantation in mice.

    Science.gov (United States)

    Chen, Xinjian; Wang, Yuanyuan; Li, Qiuxia; Tsai, Schickwann; Thomas, Alun; Shizuru, Judith A; Cao, Thai M

    2013-08-01

    A major challenge in allogeneic bone marrow (BM) transplantation is overcoming engraftment resistance to avoid the clinical problem of graft rejection. Identifying gene pathways that regulate BM engraftment may reveal molecular targets for overcoming engraftment barriers. Previously, we developed a mouse model of BM transplantation that utilizes recipient conditioning with non-myeloablative total body irradiation (TBI). We defined TBI doses that lead to graft rejection, that conversely are permissive for engraftment, and mouse strain variation with regards to the permissive TBI dose. We now report gene expression analysis, using Agilent Mouse 8x60K microarrays, in spleens of mice conditioned with varied TBI doses for correlation to the expected engraftment phenotype. The spleens of mice given engrafting doses of TBI, compared with non-engrafting TBI doses, demonstrated substantially broader gene expression changes, significant at the multiple testing-corrected P change ≥2. Functional analysis revealed significant enrichment for a down-regulated canonical pathway involving B-cell development. Genes enriched in this pathway suggest that suppressing donor antigen processing and presentation may be pivotal effects conferred by TBI to enable engraftment. Regardless of TBI dose and recipient mouse strain, pervasive genomic changes related to inflammation was observed and reflected by significant enrichment for canonical pathways and association with upstream regulators. These gene expression changes suggest that macrophage and complement pathways may be targeted to overcome engraftment barriers. These exploratory results highlight gene pathways that may be important in mediating BM engraftment resistance.

  3. Subclinical pulmonary function defects following autologous and allogeneic bone marrow transplantation: relationship to total body irradiation and graft-versus-host disease

    Energy Technology Data Exchange (ETDEWEB)

    Tait, R.C.; Burnett, A.K.; Robertson, A.G.; McNee, S.; Riyami, B.M.; Carter, R.; Stevenson, R.D. (Department of Haematology, Royal Infirmary, Glasgow (Scotland))

    1991-06-01

    Pulmonary function results pre- and post-transplant, to a maximum of 4 years, were analyzed in 98 patients with haematological disorders undergoing allogeneic (N = 53) or autologous bone marrow transplantation (N = 45) between 1982 and 1988. All received similar total body irradiation based regimens ranging from 9.5 Gy as a single fraction to 14.4 Gy fractionated. FEV1/FVC as a measure of airway obstruction showed little deterioration except in patients experiencing graft-versus-host disease in whom statistically significant obstructive ventilatory defects were evident by 6 months post-transplant (p less than 0.01). These defects appeared to be permanent. Restrictive ventilatory defects, as measured by reduction in TLC, and defects in diffusing capacity (DLCO and KCO) were also maximal at 6 months post-transplant (p less than 0.01). Both were related, at least in part, to the presence of GVHD (p less than 0.01) or use of single fraction TBI with absorbed lung dose of 8.0 Gy (p less than 0.05). Fractionated TBI resulted in less marked restricted ventilation and impaired gas exchange, which reverted to normal by 2 years, even when the lung dose was increased from 11.0 Gy to between 12.0 and 13.5 Gy. After exclusion of patients with GVHD (30% allografts) there was no significant difference in pulmonary function abnormalities between autograft and allograft recipients.

  4. COMPROMISING EFFECT OF LOW DOSE-RATE TOTAL-BODY IRRADIATION ON ALLOGENEIC BONE-MARROW ENGRAFTMENT

    NARCIS (Netherlands)

    VAN OS, R; KONINGS, A W T; DOWN, J D

    1993-01-01

    The protraction of total body irradiation (TBI) to a continuous low dose-rate has been investigated for its effect on donor marrow engraftment in murine bone marrow transplant (BMT) models of varying histocompatibility. Three different BMT combinations were used: syngeneic [B6-Gpi-1a --> B6-Gpi-1b],

  5. Successful treatment with intravesical cidofovir for virus-associated hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation: A case report and a review of the literature.

    Science.gov (United States)

    Sakurada, Maki; Kondo, Tadakazu; Umeda, Masayuki; Kawabata, Hiroshi; Yamashita, Kouhei; Takaori-Kondo, Akifum

    2016-07-01

    Virus-associated hemorrhagic cystitis (VAHC) is a formidable complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The standard management of severe VAHC after allo-HSCT has not been established. Intravenous administration of cidofovir (CDV), an acyclic nucleoside analogue with broad-spectrum activity against DNA viruses, has been reported to be effective for VAHC, but it can cause severe renal toxicity. Here we report four cases who achieved clinical responses with intravesical instillation of CDV for severe VAHC after allo-HSCT. Median age was 57 years (40-63), and all were male. The underlying diseases were hematological malignancies. Three had received bone marrow transplantation, and one received cord blood transplantation twice. Conditioning regimen was myeloablative for one, and reduced-intensity for three. The viral types were BK virus and/or adenovirus. Two patients had received CDV intravenously prior to the intravesical therapy. A dose of intravesical CDV was 2-5 mg/kg. In all cases, symptoms of cystitis improved dramatically within a few days without showing any systemic adverse effects. The virological response was observed in two cases. This local therapy was effective even in the cases refractory to the intravenous CDV and a case with severe renal failure. Along with the review of literature, we propose that the intravesical instillation of CDV can be a therapeutic option for severe VAHC after allo-HSCT. Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  6. Allogeneic mesenchymal progenitor cells for posterolateral lumbar spine fusion in sheep.

    Science.gov (United States)

    Wheeler, Donna L; Lane, Joseph M; Seim, Howard B; Puttlitz, Christian M; Itescu, Silviu; Turner, A Simon

    2014-03-01

    Osteoconductive porous ceramic bone graft materials supplemented with mesenchymal precursor cells (MPC) derived from autologous bone marrow aspirates have been shown to stimulate successful interbody and posterolateral spine fusion in preclinical models. Recent advances in immunomagnetic cell sorting have enabled purification and isolation of pluripotent stem cells from marrow aspirates and have expanded stem cell technology to allogeneic cell sources. Allogeneic MPC technology combined with appropriate synthetic biomaterial carriers could provide both the osteogenic and osteoconductive components needed for successful posterolateral spine fusion without the need for autologous bone harvest or expensive recombinant protein technology. To determine the safety and efficacy of a hydroxyapatite:tricalcium phosphate graft material supplemented with allogeneic mesenchymal precursor cells in posterolateral lumbar spine fusion using an ovine model. Skeletally mature ewes underwent single-level instrumented posterolateral lumbar spine fusion using either autograft (AG), hydroxyapatite:tricalcium phosphate carrier (CP), or CP supplemented with allogeneic mesenchymal progenitor cells (MPCs). Three doses of MPCs were evaluated: 25 × 10⁶ cells (low dose, LD), 75 × 10⁶ cells (mid dose, MD), and 225 × 10⁶ cell (high dose, HD). Animals survived for either 4 or 9 months. Plain radiographs were acquired and scored for bridging bone at regular intervals during healing to monitor fusion development. Hematology, coagulation, and serum chemistry were monitored at regular intervals throughout the study to monitor animal health. After necropsy, computed tomography, high-resolution radiography, biomechanical testing, organ pathology, bone histopathology, and bone histomorphometry were conducted to monitor the safety and ascertain the efficacy of MPC treatment. MPC treatment in this spine fusion model resulted in no observed adverse systemic or local tissue responses

  7. [Analysis of chronergy for treatment of spinal cord injury with the allogeneic bone mesenchymal stem cells (BMscs) transplantation in rats].

    Science.gov (United States)

    Duan, Da-peng; Su, Quan; Hu, Wei; You, Wu-Lin; Dang, Xiao-Qian; Wang, Kun-Zheng

    2013-10-01

    ,and different gliocyte proliferation and inflammatory cell infiltrate cound be found. Allogeneic BMSCs transplantation is effective to stimulate the recovery of spinal cord function in rats with spinal cord injury,and the optimal time of BMSCs transplantation maybe at the 3 d after injury.

  8. Annual bone loss and success rates of dental implants based on radiographic measurements

    NARCIS (Netherlands)

    Geraets, W.; Zhang, L.; Liu, Y.; Wismeijer, D.

    2014-01-01

    Objectives: Bone loss around dental implants is generally measured by monitoring changes in marginal bone level using radiographs. After the first year of implantation, an implant should have <0.2 mm annual loss of marginal bone level to satisfy the criteria of success. However, the process of

  9. Cytogenetic evidence for recurrence of acute myelogenous leukemia after allogeneic bone marrow transplantation in donor hematopoietic cells

    Energy Technology Data Exchange (ETDEWEB)

    Elfenbein, G.J.; Brogaonkar, D.S.; Bias, W.B.

    1978-09-01

    A 22-yr-old man with acute myelocytic leukemia received a bone marrow transplant from a genotypically HLA-identical female sibling after cyclophosphamide preparation. He remained in complete remission for 18 mo, when he developed a chloroma in the perineum. The chloroma was treated with local radiotherapy. The chloroma recurred 8 mo later and was treated with radiotherapy followed by combination chemotherapy. At 34 mo after transplant, marrow relapse and chloroma were documented. The first chloroma contained host cells by fluorescent Y-chromatin body analyses of interphase nuclei. All metaphase cells and karyotypes from peripheral blood and marrow samples showed no evidence of host cells from 3 wk after transplant through the time of marrow relapse. Data from autosomal and sex chromosome studies indicate that the marrow relapse occurred in cells of donor origin. A new consistent chromosome abnormality (45, X, -X, t(8;21) (q22; q22)) was observed in a majority of donor cells. The patient received a second bone marrow transplant from the same donor after preparation with busulfan and cyclophosphamide and attained a complete remission with full hematologic engraftment.

  10. Chronic active Epstein-Barr virus infection (CAEBV) successfully treated with allogeneic peripheral blood stem cell transplantation.

    Science.gov (United States)

    Taketani, T; Kikuchi, A; Inatomi, J; Hanada, R; Kawaguchi, H; Ida, K; Oh-Ishi, T; Arai, T; Kishimoto, H; Yamamoto, K

    2002-03-01

    We report a pediatric case of CAEBV and T cell-based Hodgkin's-like disease successfully treated with allo PBSCT from an HLA-matched sibling. The diagnosis of CAEBV was made from clinical signs and the presence of the EBV genome in PBMC and tumor cells. Conditioning with busulfan (BU) + etoposide (VP16) + cyclophosphamide (CY) was effective and well tolerated. EBV was totally eradicated by 3 months after allo PBSCT. Although she suffered from chronic GVHD of the liver, she has been well and free of disease for 47 months since PBSCT. We suggest allo PBSCT for CAEBV as a potent therapeutic strategy for eradication of the EBV genome and allowing immunological reconstitution.

  11. Bone Marrow Graft-Versus-Host Disease in Major Histocompatibility Complex-Matched Murine Reduced-Intensity Allogeneic Hemopoietic Cell Transplantation.

    Science.gov (United States)

    Shahin, Kifah; Mattar, Zamil; Silveira, Pablo; Hsu, Wei-Hsun; Bendall, Linda; Hart, Derek; Bradstock, Kenneth F

    2017-11-01

    Most clinical allogeneic hemopoietic cell transplants (alloHCT) are now performed using reduced-intensity conditioning (RIC) instead of myeloablative conditioning (MAC); however, the biology underlying this treatment remains incompletely understood. We investigated a murine model of major histocompatibility complex-matched multiple minor histocompatibility antigen-mismatched alloHCT using bone marrow (BM) cells and splenocytes from B6 (H-2) donor mice transplanted into BALB.B (H-2) recipients after RIC with fludarabine of 100 mg/kg per day for 5 days, cyclophosphamide of 60 mg/kg per day for 2 days, and total body irradiation (TBI). The lowest TBI dose capable of achieving complete donor chimerism in this mouse strain combination was 325 cGy given as a single fraction. Mice that underwent RIC had a reduced incidence and delayed onset of graft-versus-host disease (GVHD) and significantly prolonged survival compared with MAC-transplanted recipients (TBI of 850 cGy plus cyclophosphamide of 60 mg/kg per day for 2 days). Compared with syngeneic controls, RIC mice with GVHD showed evidence of BM suppression, have anemia, reduced BM cellularity, and showed profound reduction in BM B cell lymphopoiesis associated with damage to the endosteal BM niche. This was associated with an increase in BM CD8 effector T cells in RIC mice and elevated blood and BM plasma levels of T helper1 cytokines. Increasing doses of splenocytes resulted in increased incidence of GVHD in RIC mice. We demonstrate that the BM is a major target organ of GVHD in an informative clinically relevant RIC mouse major histocompatibility complex-matched alloHCT model by a process that seems to be driven by CD8 effector T cells.

  12. Allogeneic stem cells from deciduous teeth in treatment for periodontitis in miniature swine.

    Science.gov (United States)

    Fu, Xiaoru; Jin, Luyuan; Ma, Ping; Fan, Zhipeng; Wang, Songlin

    2014-06-01

    Regeneration of lost periodontium in periodontitis is a challenge in that alveolar bone, cementum, and periodontal ligament need to be restored to their original architecture. Stem cells from exfoliated deciduous teeth (SHEDs) appear to be an attractive candidate for periodontium tissue regeneration. Previously, the authors successfully regenerated periodontal defects using autologous and allogeneic periodontal ligament stem cells (PDLSCs). The purpose of the present study is to investigate the ability of allogeneic SHEDs to regenerate lost periodontium in a swine periodontitis model. Animal models of periodontitis were established in miniature pigs, and allogeneic stem cells were isolated from miniature pig deciduous teeth (SPDs). The animal models were treated with SPDs plus hydroxyapatite/tricalcium phosphate (HA/TCP). Allogeneic PDLSCs plus HA/TCP or HA/TCP alone were set as positive control or control, respectively. Clinical assessments, computed tomography (CT) scanning, and histologic examination were used to evaluate the outcome of tissue regeneration. Clinical indices including probing depth, gingival recession, and attachment loss showed significant restoration in the SPD and PDLSC treatment groups, compared to the HA/TCP group 12 weeks post-transplantation. Meanwhile, CT scans showed that 75% of the samples had successful hard-tissue regeneration in both PDLSC and SPD groups, compared to the HA/TCP group, where the success rate was only 25%. In addition, histologic examination demonstrated that SPD and PDLSC treatment brought about remarkable regeneration of periodontal tissues, whereas periodontal regeneration was rare in the HA/TCP group. Allogeneic SPDs can effectively repair hard and soft tissue loss brought about by periodontitis in a swine model. Allogeneic SHEDs, which are easily accessible, may be applied to treat periodontitis in clinics in the future.

  13. ALLOGENEIC PERIPHERAL BLOOD AND BONE MARROW STEM CELL TRANSPLANTATION FOR CHRONIC MYELOGENOUS LEUKEMIA: A SINGLE CENTER STUDY

    Directory of Open Access Journals (Sweden)

    A. Ghavamzadeh

    2003-08-01

    Full Text Available In this center, from 1991 to 2002, 89 chronic myelogenous leukemic (CML patients, age ranging between 8-48 years with a median age of 29, underwent hematopoietic stem cell transplantation. Eighty-eight patients were in the first chronic phase of disease. Twenty-three patients received bone marrow transplantation (BMT and 66 patients received peripheral blood stem cell transplantations (PBSCT. Transplantation was performed at a median interval of 19 months post-diagnosis. All with five exceptions received busulfan + cyclophosphamide (Bu Cy conditioning regimens. To maintain graft vs. host disease (GVHD prophylaxis, all with three exceptions received cyclosporine + metothrexate. Administration of granulocyte colony stimulating factor (G-CSF, per protocol, was included in post-transplantation regimens from the year 1999 on 48 patients. All patients received marrow transplantations from sibling donors. Fifty seven of transplanted patients are alive. Disease free survivals (DFS from 6.2 to 9.5 and from 2.2 to 6.2 years for BMT group were 38.2% and 47.8%, respectively. DFS for PBSCT group was calculated as 54.3% in a period of 1.9 to 4.6 years.

  14. Enhanced cellular responses of human bone marrow stromal cells cultured on pretreated surface with allogenic platelet-rich plasma.

    Science.gov (United States)

    Shin, Seung Han; Yoo, Jeong Joon; Kim, Ha Na; Nam, Jinwoo; Kim, Hee Joong

    2012-01-01

    The principal objective of this study was to evaluate the effects of surface pretreatment with platelet-rich plasma (PRP) on the cellular functions of human bone marrow stromal cells (hBMSCs). The surfaces of tissue culture plates (TCPs) were pretreated by adding PRP followed by centrifugation to bring platelets closer to the surface, followed by incubation for 60 min at 37°C. Then, hBMSCs were seeded onto TCP and TCP pretreated with PRP (TCP-PRP), followed by culture in osteogenic medium. Cell attachment, proliferation, and osteogenic differentiation were evaluated. Field emission scanning electron microscope (FE-SEM; JSM-7401F, JEOL Ltd., Japan) observations were conducted. The attachment of hBMSCs was significantly lower on TCP-PRP than on TCP. However, when the cell numbers were normalized with those observed on day 1 of culture, cellular proliferation on 5 days was significantly higher on TCP-PRP. Alkaline phosphatase activity, an index of early phase of osteoblastic differentiation, was significantly higher on TCP-PRP on day 14. Calcium deposition amount, an index of terminal osteoblastic differentiation, was also significantly higher on TCP-PRP on days 14 and 21. The results of von Kossa staining confirmed that, on day 21, the area of mineralized nodules was significantly larger on TCP-PRP. FE-SEM observation demonstrated that activated platelets and fibrin network covered the surface after PRP treatment. An increase in the number of hBMSCs and their cellular products was evident on the FE-SEM observation, and the fibrin network remained on day 21. Our results demonstrate that a PRP-treated surface enhanced early proliferation and late osteogenic differentiation of hBMSCs.

  15. Prolonged Survival of Subcutaneous Allogeneic Islet Graft by Donor Chimerism without Immunosuppressive Treatment

    Directory of Open Access Journals (Sweden)

    Brend Ray-Sea Hsu

    2017-01-01

    Full Text Available The aim of this study was to investigate whether tolerance-induced protection of islets in the renal subcapsular space can also prevent subcutaneous allogeneic islets from being rejected. We used bone marrow stem cells from C57BL/6 (H2b mice to construct donor chimerism in conditioned diabetic BALB/c (H2d mice and investigated the effect of donor chimerism on engraftment and survival of subcutaneously transplanted allogeneic islets in streptozotocin-induced diabetic mice. We also studied the anti-inflammatory effect of mesenchymal stem cell on islet engraftment. Full but not low-grade or no donor chimerism was associated with successful engraftment of allogeneic islets and restoration of normoglycemia in the treated diabetic mice. The temporary hyperglycemia was 11 ± 1 versus 19 ± 5 days (p<0.05 for the mice with full donor chimerism with transplanted islets in the renal subcapsular space versus the subcutaneous space, respectively. Cotransplantation of mesenchymal stem cell did not enhance alloislet engraftment. Full multilineage donor chimerism was associated with a higher transient expansion of CD11b+ and Gr-1+ myeloid progenitor cells and effector memory CD4 and CD8 T cells. In conclusion, full donor chimerism protected both renal subcapsular and subcutaneous allogeneic islets in this rodent transplantation model.

  16. Crestal bone preservation: A review of different approaches for successful implant therapy

    Directory of Open Access Journals (Sweden)

    D Krishna Prasad

    2011-01-01

    The purpose of this paper is to review all the possible methods to preserve the crestal bone, when each method should be used and their success rates in an attempt to address this complex problem of crestal bone resorption. "PubMed" and "Google Scholar" were used to find out any studies involving platform switching concept from 1990 up to 2009. Twenty-four studies involving methods for preservation of crestal bone were evaluated, which included 26% studies on platform switching, 22% on non-submerged approach, 17% on scalloped implants, 13% on progressive loading and 22% on immediate implant placement. Crestal bone preservation should be thought of starting from the design of the implant to be placed. The technique to be followed in a given case will depend upon the density of bone, force factors by the patient, bone volume and amount of soft tissues, etc. The best possible method or the combination of the methods should be used to preserve the crestal bone for the long-term success of the implants.

  17. Prediction of autosomal STR typing success in ancient and Second World War bone samples.

    Science.gov (United States)

    Zupanič Pajnič, Irena; Zupanc, Tomaž; Balažic, Jože; Geršak, Živa Miriam; Stojković, Oliver; Skadrić, Ivan; Črešnar, Matija

    2017-03-01

    Human-specific quantitative PCR (qPCR) has been developed for forensic use in the last 10 years and is the preferred DNA quantification technique since it is very accurate, sensitive, objective, time-effective and automatable. The amount of information that can be gleaned from a single quantification reaction using commercially available quantification kits has increased from the quantity of nuclear DNA to the amount of male DNA, presence of inhibitors and, most recently, to the degree of DNA degradation. In skeletal remains samples from disaster victims, missing persons and war conflict victims, the DNA is usually degraded. Therefore the new commercial qPCR kits able to assess the degree of degradation are potentially able to predict the success of downstream short tandem repeat (STR) typing. The goal of this study was to verify the quantification step using the PowerQuant kit with regard to its suitability as a screening method for autosomal STR typing success on ancient and Second World War (WWII) skeletal remains. We analysed 60 skeletons excavated from five archaeological sites and four WWII mass graves from Slovenia. The bones were cleaned, surface contamination was removed and the bones ground to a powder. Genomic DNA was obtained from 0.5g of bone powder after total demineralization. The DNA was purified using a Biorobot EZ1 device. Following PowerQuant quantification, DNA samples were subjected to autosomal STR amplification using the NGM kit. Up to 2.51ng DNA/g of powder were extracted. No inhibition was detected in any of bones analysed. 82% of the WWII bones gave full profiles while 73% of the ancient bones gave profiles not suitable for interpretation. Four bone extracts yielded no detectable amplification or zero quantification results and no profiles were obtained from any of them. Full or useful partial profiles were produced only from bone extracts where short autosomal (Auto) and long degradation (Deg) PowerQuant targets were detected. It is

  18. Ex Vivo Oncolytic Virotherapy with Myxoma Virus Arms Multiple Allogeneic Bone Marrow Transplant Leukocytes to Enhance Graft versus Tumor

    OpenAIRE

    Lilly, Cameron L.; Villa, Nancy Y.; Lemos de Matos, Ana; Ali, Haider M.; Dhillon, Jess-Karan S.; Hofland, Tom; Rahman, Masmudur M.; Chan, Winnie; Bogen, Bjarne; Cogle, Christopher; McFadden, Grant

    2017-01-01

    Allogeneic stem cell transplant-derived T cells have the potential to seek and eliminate sites of residual cancer that escaped primary therapy. Oncolytic myxoma virus (MYXV) exhibits potent anti-cancer efficacy against human cancers like multiple myeloma (MM) and can arm transplant-derived T cells to become more effective cancer killers in vitro and in an immunodeficient xenotransplant murine model. Here, we tested ex vivo MYXV virotherapy against residual murine MM in immunocompetent mice us...

  19. Eculizumab before and after allogeneic hematopoietic stem cell transplantation in a patient with paroxysmal nocturnal hemoglobinuria

    Directory of Open Access Journals (Sweden)

    Hakan Göker

    2011-09-01

    Full Text Available Paroxysmal nocturnal hemoglobinuria (PNH is characterized by the triad of intravascular hemolysis, venous thrombosis, and cytopenia. Treatment of PNH is generally supportive. Bone marrow transplantation is the only curative therapy for PNH, but is associated with significant morbidity and mortality. Herein, we present a patient with PNH that received eculizumab, a humanized monoclonal antibody that blocks activation of the terminal complement at C5, before and immediately following allogeneic peripheral stem cell transplantation. Prior to hematopoietic stem cell transplantation eculizumab treatment markedly reduced hemolysis and transfusion requirement; however, 1 d post transplantation a hemolytic episode occured, which was successfully stopped with eculizumab re-treatment. Afterwards the patient did not require additional transfusions. The results of this study indicate that early administration of eculizumab may be a safe and effective therapy for hemolytic episodes associated with allogeneic peripheral stem cell transplantation in patients with PNH.

  20. Chemokine Receptor Signatures in Allogeneic Stem Cell Transplantation

    Science.gov (United States)

    2015-08-01

    Porter DL (2015). “Reduced-intensity conditioning for allogeneic hematopoietic stem-cell transplantation in adults with acute myeloid leukemia .” Bone...Tallman MS, Wirk B, Bunjes DW, Devine SM, de Lima M, Weisdorf DJ, Uy GL (2015). “Allogeneic Hematopoietic Cell Transplant for Acute Myeloid Leukemia ...in target organs of GVHD. 15. SUBJECT TERMS CCR5, Chemokines, graft-versus-host disease 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT

  1. Two cases of chronic active Epstein-Barr virus infection in which EBV-specific cytotoxic T lymphocyte was induced after allogeneic bone marrow transplantation.

    Science.gov (United States)

    Miyamura, Takako; Chayama, Kousuke; Wada, Tomoaki; Yamaguchi, Kazunari; Yamashita, Nobuko; Ishida, Toshiaki; Washio, Kana; Morishita, Naoto; Manki, Akira; Oda, Megumi; Morishima, Tsuneo

    2008-08-01

    CAEBV is a high mortality and morbidity disease with life-threatening complications. Nevertheless, the treatment regimens for CAEBV have not yet been established. Although some reports have described CAEBV therapy involving treatments such as antiviral drugs, immunomodulatory agents, and immunochemotherapy, none of these treatments have been demonstrated to be effective. The only treatment reported to be effective is allogeneic SCT. However, the complications of SCT are severe, so treatment results have been poor. Recently, immunotherapy has been devised, but this is still in the developmental stage. In this report, two cases of CAEBV in which allogeneic SCT was performed soon after diagnosis are reported. In both cases, a high EBV genome titer in the peripheral blood was detected at onset. After SCT, the EBV genome titer decreased as CTL activity gradually increased. This fact suggested that not only high-dose chemotherapy as a preconditioning treatment of SCT but also increased CTL activity which could eliminate virus-infected cells might be effective, although additional cases should be studied in order to establish effective treatments.

  2. Successful bone-anchored hearing aid implantation in a patient with osteogenesis imperfecta.

    Science.gov (United States)

    Coutinho, M B; Marques, C; Mendes, G J; Gonçalves, C

    2015-11-01

    To report a case of successful bone-anchored hearing aid implantation in an adult patient with type III osteogenesis imperfecta, which is commonly regarded as a contraindication to this procedure. A 45-year-old man with type III osteogenesis imperfecta presented with mixed hearing loss. There was a mild sensorineural component in both ears, with an air-bone gap between 45 and 50 dB HL. He was implanted with a bone-anchored hearing aid. The audiological outcome was good, with no complications and good implant stability (as measured by resonance frequency analysis). To our knowledge, this is the first recorded case of bone-anchored hearing aid implantation in a patient with osteogenesis imperfecta.

  3. Platelet transfusion refractoriness attributable to HLA antibodies produced by donor-derived cells after allogeneic bone marrow transplantation from one HLA-antigen-mismatched mother.

    Science.gov (United States)

    Hatakeyama, Naoki; Hori, Tsukasa; Yamamoto, Masaki; Inazawa, Natsuko; Iesato, Kotoe; Miyazaki, Toru; Ikeda, Hisami; Tsutsumi, Hiroyuki; Suzuki, Nobuhiro

    2011-12-01

    PTR is a serious problem in patients being treated for hematologic disorders. Two patients with acute leukemia developed PTR after allogeneic BMT from one HLA-antigen-mismatched mother attributable to HLA antibodies, which could not be detected in their serum before BMT. HLA antibodies, whose specificity resembled that of each patient, were detected in each donor's serum. Each donor had probably been immunized during pregnancy by their partner's HLA antigens expressed by the fetus, consequently, transplanted donor-derived cells provoked HLA antibodies in each recipient early after BMT, and those HLA antibodies induced PTR. If the mothers are selected as donors for their children, they should be tested for the presence of HLA antibodies. © 2010 John Wiley & Sons A/S.

  4. Computed tomography-guided percutaneous biopsy of bone lesions: rate of diagnostic success and complications

    Energy Technology Data Exchange (ETDEWEB)

    Maciel, Macello Jose Sampaio; Tyng, Chiang Jeng; Barbosa, Paula Nicole Vieira Pinto; Bitencourt, Almir Galvao Vieira; Matushita Junior, Joao Paulo Kawaoka; Zurstrassen, Charles Edouard; Chung, Wu Tu; Chojniak, Rubens, E-mail: macellomaciel@me.com [A.C.Camargo Cancer Center, Sao Paulo, SP (Brazil)

    2014-09-15

    Objective: To determine the rates of diagnostic success and complications of computed tomography (CT)-guided percutaneous biopsy of bone lesions suspected for malignancy. Materials and Methods: Retrospective study including 186 cases of CT-guided percutaneous biopsies of bone lesions in the period from January, 2010 to December, 2012. All the specimens were obtained with 8-10 gauge needles. The following data were collected: demographics, previous history of malignancy, data related to the lesion, to the procedure, and to histological results. Results: Most patients were women (57%), and the mean age was 53.0 ± 16.4 years. In 139 cases (74.6%), there was diagnostic suspicion of metastasis and the most common primary tumors were breast (32.1%) and prostate (11.8%). The bones most commonly involved were spine (36.0%), hip (32.8%) and long bones (18.3%). Complications occurred in only three cases (1.6%) including bone fracture, paraesthesia with functional impairment, and needle breakage requiring surgical removal. The specimens collected from 183 lesions (98.4%) were considered appropriate for diagnosis. Malignant results were more frequently found in patients who had a suspected secondary lesion and history of known malignancy (p < 0.001), and in patients who underwent PET/CT-guided procedures (p = 0.011). Conclusion: CT-guided percutaneous biopsy is a safe and effective procedure for the diagnosis of suspicious bone lesions. (author)

  5. [Percutaneous sclerotherapy with polidocanol : Successful relapse therapy of infantile aneurysmal bone cyst].

    Science.gov (United States)

    Rieger, S; Dickschas, J

    2016-09-01

    The aneurysmal bone cyst (ABC) is well-known for its local expansile growth form and for the high risk of recurrence after treatment. We present the case of a 6‑year-old patient with a large ABC in the metaphysis of the proximal tibia, which showed recurrence only five months after treatment with curettage and autologous bone graft. By using six percutaneous intralesional injections of polidocanol the patient was successfully treated with no recurrence. After 18 months, a mild genu valgum was clinically noted.

  6. Successful use of oseltamivir prophylaxis in managing a nosocomial outbreak of influenza A in a hematology and allogeneic stem cell transplant unit.

    Science.gov (United States)

    Yue, Mimi C; Collins, Joel T; Subramoniapillai, Elango; Kennedy, Glen A

    2017-02-01

    To describe a nosocomial outbreak of H1N1 influenza A in an inpatient hematology and allogeneic stem cell transplant unit and outcomes of universal oseltamivir prophylaxis. Medical records of all patients admitted to the unit were reviewed to define the nosocomial outbreak, commencing 1 week prior to the index case until 4 weeks following institution of oseltamivir prophylaxis. Timelines for clinical symptoms, viral spread, management, patient outcomes and follow up testing were constructed. All cases of influenza were confirmed on nasopharyngeal swabs and/or bronchoalveolar lavages collected for polymerase chain reaction testing. In addition to the index case, further 11 patients were diagnosed with influenza A during the outbreak. Six patients (50%) had influenza-like-illness, five (42%) had respiratory symptoms only and one (8%) was asymptomatic. In total, five patients died, including four (33%) patients who were admitted to intensive care. A clustering of seven cases led to recognition of the outbreak and subsequent commencement of universal prophylaxis with oseltamivir 75 mg/day in all inpatients within the unit. Strict infection control processes were reinforced concurrently. There were no further cases of influenza A linked to the outbreak after the implementation of universal oseltamivir prophylaxis. Three later cases were linked to H1N1 exposure during the original outbreak. H1N1 influenza infection is associated with significant mortality in hematology patients. Universal prophylaxis with oseltamivir during a nosocomial outbreak appeared to be effective in controlling spread of the virus. We recommend early institution of infection control and universal prophylaxis in any nosocomial outbreak of influenza. © 2016 John Wiley & Sons Australia, Ltd.

  7. [Remembering the first successful bone marrow transplantation performed in 1977 in Novi Sad].

    Science.gov (United States)

    Popović, K

    1998-01-01

    The author describes circumstances under which a young man with a severe idiopathic aplastic anemia, pancytopenia and hemorrhagic syndrome had undergone the first successful bone marrow transplantation performed at the Department of Haematology of the Internal Clinic in Novi Sad in 1977. As the patient did not react to the androgenic therapy and he had a healthy twin-brother with the same blood group and HLA system and MCL, differing only in Rh genotype, bone marrow transplantation was suggested. Attempted transplantation without immunosuppression and with a small number of bone marrow cells was performed in 1976 at the Military Medical Academy (MMA) in Belgrade, but it was unsuccessful. The patient suffered from a serious pancytopenia and hemorrhagic syndrome, and survived due to blood transfusions. There were 56 blood transfusions with more than 20 liters of blood. At that time bone marrow transplantations were not performed in Yugoslavia, only MMA started this method. The patient could not be transported, so the author with his associates decided to perform a new transplantation with immunosuppressive therapy with cyclophosphamide and with sufficient number of bone marrow cells, believing that it was the only chance their patient had to get better. Without special equipment, improvising a sterile room, the author performed a new transplantation. Two weeks later first signs of improvement of pancytopenia occurred, whereas after reticulocytic crisis, 45 days later, the number of blood cells reached normal values. On the occasion of examining Rh genotype of our patient it was established that, instead of previous Rh genotype inherited from his father, after retransplantation he had a new Rh phenotype acquired from his brother who inherited it from their mother. It was a proof that the transplantation was a complete success. On the occasion of 20th anniversary of that event in 1977, the whole team, which had performed the retransplantation, met their ex

  8. Successful disinfection of femoral head bone graft using high hydrostatic pressure.

    Science.gov (United States)

    van de Sande, Michiel A J; Bovée, Judith V M G; van Domselaar, Mark; van Wijk, Marja J; Sanders, Ingrid; Kuijper, Ed

    2017-12-20

    The current standard for sterilization of potentially infected bone graft by gamma irradiation and thermal or chemical inactivation potentially deteriorates the biomechanical properties of the graft. We performed an in vitro experiment to evaluate the use of high hydrostatic pressure (HHP); which is widely used as a disinfection process in the food processing industry, to sterilize bone grafts. Four femoral heads were divided into five parts each, of which 16 were contaminated (in duplicate) with 10 5 -10 7  CFU/ml of Staphylococcus epidermidis, Bacillus cereus, or Pseudomonas aeruginosa or Candida albicans, respectively. Of each duplicate, one sample was untreated and stored similarly as the treated sample. The remaining four parts were included as sterile control and non-infected control. The 16 parts underwent HHP at the high-pressure value of 600 MPa. After HHP, serial dilutions were made and cultured on selective media and into enrichment media to recover low amounts of microorganism and spores. Three additional complete femoral heads were treated with 0, 300 and 600 MPa HHP respectively for histological evaluation. None of the negative-control bone fragments contained microorganisms. The measured colony counts in the positive-control samples correlated excellent with the expected colony count. None of the HHP treated bone fragments grew on culture plates or enrichment media. Histological examination of three untreated femoral heads showed that the bone structure remained unchanged after HHP. Sterilizing bone grafts by high hydrostatic pressure was successful and is a promising technique with the possible advantage of retaining biomechanical properties of bone tissue.

  9. Allogeneic major histocompatibility complex-mismatched equine bone marrow-derived mesenchymal stem cells are targeted for death by cytotoxic anti-major histocompatibility complex antibodies.

    Science.gov (United States)

    Berglund, A K; Schnabel, L V

    2017-07-01

    Allogeneic mesenchymal stem cells (MSCs) are a promising cell source for treating musculoskeletal injuries in horses. Controversy exists, however, over whether major histocompatibility complex (MHC)-mismatched MSCs are recognised by the recipient immune system and targeted for death by a cytotoxic antibody response. To determine if cytotoxic anti-MHC antibodies generated in vivo following MHC-mismatched MSC injections are capable of initiating complement-dependent cytotoxicity of MSCs. Experimental controlled study. Antisera previously collected at Days 0, 7, 14 and 21 post-injection from 4 horses injected with donor MHC-mismatched equine leucocyte antigen (ELA)-A2 haplotype MSCs and one control horse injected with donor MHC-matched ELA-A2 MSCs were utilised in this study. Antisera were incubated with ELA-A2 MSCs before adding complement in microcytotoxicity assays and cell death was analysed via eosin dye exclusion. ELA-A2 peripheral blood leucocytes (PBLs) were used in the assays as a positive control. Antisera from all 4 horses injected with MHC-mismatched MSCs contained antibodies that caused the death of ELA-A2 haplotype MSCs in the microcytotoxicity assays. In 2 of the 4 horses, antibodies were present as early as Day 7 post-injection. MSC death was consistently equivalent to that of ELA-A2 haplotype PBL death at all time points and antisera dilutions. Antisera from the control horse that was injected with MHC-matched MSCs did not contain cytotoxic ELA-A2 antibodies at any of the time points examined. This study examined MSC death in vitro only and utilized antisera from a small number of horses. The cytotoxic antibody response induced in recipient horses following injection with donor MHC-mismatched MSCs is capable of killing donor MSCs in vitro. These results suggest that the use of allogeneic MHC-mismatched MSCs must be cautioned against, not only for potential adverse events, but also for reduced therapeutic efficacy due to targeted MSC death. © 2016 The

  10. Titanium implant insertion into dog alveolar ridges augmented by allogenic material

    DEFF Research Database (Denmark)

    Pinholt, E M; Haanaes, H R; Donath, K

    1994-01-01

    of 6 weeks allogenic, demineralized and lyophilized dentin or bone was implanted subperiosteally. Titanium implants were installed 5.5 months later in some of the regions. Light and fluorescence microscopic evaluation revealed fibrous encapsulation of the implanted allogenic material, no osteoinduction...

  11. Prospective clinical and radiographic evaluation of an allogeneic bone matrix containing stem cells (Trinity Evolution® Viable Cellular Bone Matrix) in patients undergoing two-level anterior cervical discectomy and fusion.

    Science.gov (United States)

    Peppers, Timothy A; Bullard, Dennis E; Vanichkachorn, Jed S; Stanley, Scott K; Arnold, Paul M; Waldorff, Erik I; Hahn, Rebekah; Atkinson, Brent L; Ryaby, James T; Linovitz, Raymond J

    2017-04-26

    Trinity Evolution® (TE), a viable cellular bone allograft, previously demonstrated high fusion rates and no safety-related concerns after single-level anterior cervical discectomy and fusion (ACDF) procedures. This prospective multicenter clinical study was performed to assess the radiographic and clinical outcomes of TE in subjects undergoing two-level ACDF procedures. In a prospective, multicenter study, 40 subjects that presented with symptomatic cervical degeneration at two adjacent vertebral levels underwent instrumented ACDF using TE autograft substitute in a polyetherethereketone (PEEK) cage. At 12 months, radiographic fusion status was evaluated by dynamic motion plain radiographs and thin cut CT with multiplanar reconstruction by a panel that was blinded to clinical outcome. Fusion success was defined by angular motion (≤4°) and the presence of bridging bone across the adjacent vertebral endplates. Clinical pain and function assessments included the Neck Disability Index (NDI), neck and arm pain as evaluated by visual analog scales (VAS), and SF-36 at both 6 and 12 months. At both 6 and 12 months, all clinical outcome scores (SF-36, NDI, and VAS pain) improved significantly (p Trinity Evolution in Anterior Cervical Disectomy and Fusion (ACDF) NCT00951938.

  12. Bilateral Transplantation of Allogenic Adult Human Bone Marrow-Derived Mesenchymal Stem Cells into the Subventricular Zone of Parkinson’s Disease: A Pilot Clinical Study

    Directory of Open Access Journals (Sweden)

    N. K. Venkataramana

    2012-01-01

    Full Text Available The progress of PD and its related disorders cannot be prevented with the medications available. In this study, we recruited 8 PD and 4 PD plus patients between 5 to 15 years after diagnosis. All patients received BM-MSCs bilaterally into the SVZ and were followed up for 12 months. PD patients after therapy reported a mean improvement of 17.92% during “on” and 31.21% during “off” period on the UPDRS scoring system. None of the patients increased their medication during the follow-up period. Subjectively, the patients reported clarity in speech, reduction in tremors, rigidity, and freezing attacks. The results correlated with the duration of the disease. Those patients transplanted in the early stages of the disease (less than 5 years showed more improvement and no further disease progression than the later stages (11–15 years. However, the PD plus patients did not show any change in their clinical status after stem cell transplantation. This study demonstrates the safety of adult allogenic human BM-MSCs transplanted into the SVZ of the brain and its efficacy in early-stage PD patients.

  13. Mesenchymal stem cells avoid allogeneic rejection

    Directory of Open Access Journals (Sweden)

    Murphy J Mary

    2005-07-01

    Full Text Available Abstract Adult bone marrow derived mesenchymal stem cells offer the potential to open a new frontier in medicine. Regenerative medicine aims to replace effete cells in a broad range of conditions associated with damaged cartilage, bone, muscle, tendon and ligament. However the normal process of immune rejection of mismatched allogeneic tissue would appear to prevent the realisation of such ambitions. In fact mesenchymal stem cells avoid allogeneic rejection in humans and in animal models. These finding are supported by in vitro co-culture studies. Three broad mechanisms contribute to this effect. Firstly, mesenchymal stem cells are hypoimmunogenic, often lacking MHC-II and costimulatory molecule expression. Secondly, these stem cells prevent T cell responses indirectly through modulation of dendritic cells and directly by disrupting NK as well as CD8+ and CD4+ T cell function. Thirdly, mesenchymal stem cells induce a suppressive local microenvironment through the production of prostaglandins and interleukin-10 as well as by the expression of indoleamine 2,3,-dioxygenase, which depletes the local milieu of tryptophan. Comparison is made to maternal tolerance of the fetal allograft, and contrasted with the immune evasion mechanisms of tumor cells. Mesenchymal stem cells are a highly regulated self-renewing population of cells with potent mechanisms to avoid allogeneic rejection.

  14. Long-term outcome of bone mineral density in children who underwent a successful liver transplantation.

    Science.gov (United States)

    D'Antiga, Lorenzo; Ballan, Donatella; Luisetto, Giovanni; Cillo, Umberto; Guariso, Graziella; Zancan, Lucia

    2004-09-27

    It has previously been shown that bone mineral density (BMD) during the first year after orthotopic liver transplantation (OLT) in children with osteodystrophy increases remarkably and according to height. The effect of posttransplant factors possibly influencing bone mass in the long-term after a successful OLT in children is unknown. Eighteen patients (9 male), median age 13.3 (range 4.7-23.7) years, median time after OLT 8.3 (1.1-17.3) years were enrolled. Indications for OLT were biliary atresia (8), Alagille (3), hepatoblastoma (2), NonA-NonG acute liver failure (2), intrahepatic cholestasis, cryptogenic cirrhosis, and cholesteryl-ester disease (1 each). At OLT, all were prepubertal and 12 were severely cholestatic. We recorded anthropometric data, immunosuppression, dual-energy x-ray absorptiometry (DXA), biochemical markers of bone metabolism, and liver function. Six children were on steroid therapy, eight were on cyclosporine, nine on tacrolimus. Median L1 to L4 spinal BMD was 0.720 (range 0.524-1.127) g/cm3, Z score -0.70 (-2.2- +2.1), height Z score -0.31 (-1.83- +1.96). Median bone mineral apparent density was 0.112 (0.084-0.142) (normal value 0.10-0.14) g/cm3. Median alanine aminotransferase level was 22 (range 11-79) IU/L, urinary free deoxypyridinolines 20.6 (7.1-62) nmol/mmol creatinine, osteocalcin 14 (2.3-45) microg/L, parathyroid hormone 51 (2-87) ng/L, Vitamin D3 67 (17-102) nmol/L. BMD after the first year from a successful pediatric liver transplantation is normal. Our study suggests that normal bone density in this setting is maintained for at least 1 decade.

  15. POSITIVE RESULTS OF TRANSPLANTATION OF MULTI-COMPONENT COMPOSITE MATERIAL CONTAINING ALLOGENEIC MESENCHYMAL STEM CELLS AFTER CYSTECTOMY IN A RABBIT

    Directory of Open Access Journals (Sweden)

    N. V. Orlovа

    2017-01-01

    Full Text Available Of late much attention has been paid to tissue engineering by urologists. After successful testing on animals, artificial urinary bladders with self-specific cells were transplanted to humans. Our research is aimed at investigating the opportunity of using cellular technologies  if no healthy  self-specific material is available.The goal of this experiment  is to investigate the opportunity of using a multi-component composite material containing  allogeneic cells to replace the defect of urinary wall under experimental conditions.The standard technique was used for isolation and culturing of mesenchymal stromal stem cells from the rabbit's  bone marrow. Multi-component composite material based on the polylactide  matrix was inoculated by allogeneic cells and transplanted in vivo to the model of partial cystectomy. In 2.5 months the presence of labeled cells in the implantation site was confirmed by objective methods.

  16. THE EFFECT OF DONOR LYMPHOCYTES-T AND TOTAL-BODY IRRADIATION ON HEMATOPOIETIC ENGRAFTMENT AND PULMONARY TOXICITY FOLLOWING EXPERIMENTAL ALLOGENEIC BONE-MARROW TRANSPLANTATION

    NARCIS (Netherlands)

    DOWN, JD; MAUCH, P; WARHOL, M; NEBEN, S; FERRARA, JLM

    1992-01-01

    To study the effects of donor T lymphocytes on engraftment and graft-versus-host disease in relation to recipient total-body irradiation, we have returned small numbers of T cells to T-cell-depleted bone marrow transplanted across a minor histocompatibility barrier in mice (B10.BR --> CBA).

  17. Encapsulation of allogeneic mesenchymal stem cells in alginate extends local presence and therapeutic function

    NARCIS (Netherlands)

    M.J.C. Leijs (Maarten J.C.); E. Villafuertes; J.C. Haeck (Joost); W.J.L.M. Koevoet (Wendy J.L.M.); B. Fernandez-Gutierrez; M.J. Hoogduijn (Martin); J.A.N. Verhaar (Jan); M.R. Bernsen (Monique); G.M. van Buul (Gerben); G.J.V.M. van Osch (Gerjo)

    2017-01-01

    textabstractBone marrow derived mesenchymal stem cells (MSCs) have immunomodulatory and trophic capacities. For therapeutic application in local chronic inflammatory diseases, MSCs, preferably of allogeneic origin, have to retain immunomodulatory properties. This might be achieved by encapsulation

  18. Evaluation of safety and efficacy of radiation-sterilized bone allografts in reconstructive oral surgery.

    Science.gov (United States)

    Krasny, Marta; Krasny, Kornel; Kamiński, Artur; Zadurska, Małgorzata; Piekarczyk, Piotr; Fiedor, Piotr

    2013-09-01

    Bone grafting allows reconstruction of the atrophied or destroyed alveolar process. In orthopaedics and traumatology allogeneic grafting has been used to restore defects of osseous tissue for over 60 years. In order to improve safety of the graft recipient, sterilized allogeneic grafts have been use. The aim of the study was to assess the direct and long-term outcomes following augmentation of atrophied alveolar processes with the use of radiation-sterilized allogeneic bone grafts. Sixty-eight patients were surgically treated between 2004 and 2011: 29 underwent open sinus floor elevation, post-extraction alveoli augmentation was performed in 16 subjects and 23 underwent reconstruction of the atrophied alveolar process. Augmentation of bone defects used bone granulate in 63 patients and bone blocks stabilized with titanium screws in 5 patients. PRF membranes collected from the patient's blood were also used in all the procedures. In each of the cases optimal dimensions of the alveolar process were obtained allowing embedment of BIOMET 3I dental implant/-s. In all the patients the defects were successfully restored with implant-supported prostheses. Radiation-sterilized allogeneic bone grafts proved to be safe and effective for the patients and manageable for the surgeon constituting a good alternative to autogeneic material.

  19. Successful Function-Preserving Therapy for Chondroblastoma of the Temporal Bone Involving the Temporomandibular Joint

    Directory of Open Access Journals (Sweden)

    Junkichi Yokoyama

    2011-02-01

    Full Text Available We present a case involving a late diagnosis of chondroblastoma of the temporal skull base involving the temporomandibular joint (TMJ. Following an initial misdiagnosis and unsuccessful treatment over a period of 5 years, the patient was referred to our department for further evaluation and possible surgical intervention for occlusal abnormalities, trismus, clicking of the TMJ, and hearing impairment. Based on preoperative immunochemical studies showing positive reaction of multinucleated giant cells for S-100 protein, the final diagnosis was chondroblastoma. The surgical approach – postauricular incision and total parotidectomy, with complete removal of the temporal bone, including the TMJ via the extended middle fossa – was successful in preserving facial nerves and diminishing clinical manifestations. This study highlights a misdiagnosed case in an effort to underline the importance of medical examinations and accurate differential diagnosis in cases involving any tumor mass in the temporal bone.

  20. Successful Treatment of Multifocal Histiocytic Sarcoma Occurring after Renal Transplantation with Cladribine, High-Dose Cytarabine, G-CSF, and Mitoxantrone (CLAG-M Followed by Allogeneic Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Julia Tomlin

    2015-01-01

    Full Text Available Histiocytic sarcoma (HS is a rare, aggressive malignancy. Lesions previously called HS were typically non-Hodgkin lymphomas, not HS. As such, chemotherapy directed at lymphoid neoplasms was frequently successful, but it is unclear if these regimens are ideal for HS. We present a 33-year-old African gentleman who underwent sequential renal transplants for glomerulonephritis. He subsequently developed HS of the upper airway and multiple cutaneous sites. The patient received cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP followed by salvage ifosfamide, carboplatin, and etoposide (ICE but had continuous progression of cutaneous involvement. Cladribine, high-dose cytarabine, G-CSF, and mitoxantrone (CLAG-M yielded a partial response with near resolution of disease. Ultimately, the patient achieved a complete remission after myeloablative allogeneic hematopoietic stem cell transplant. HS occurring after solid organ transplant raises the possibility of HS as a potential posttransplant malignancy. The use of CLAG-M has not been reported in HS. In this case, histiocyte-directed chemotherapy with CLAG-M was superior to lymphoma-directed regimens.

  1. Utility of the inspiratory phase in high-resolution computed tomography evaluations of pediatric patients with bronchiolitis obliterans after allogeneic bone marrow transplant: reducing patient radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Togni Filho, Paulo Henrique; Casagrande, Joao Luiz Marin; Lederman, Henrique Manoel, E-mail: paulotognifilho@gmail.com [Universidade Federal de Sao Paulo (EPM/UNIFESP), Sao Paulo, SP (Brazil). Escola Paulista de Medicina. Dept. of Diagnostico por Imagem; Universidade de Sao Paulo (InRad/HC/FMUSP), Sao Paulo, SP (Brazil). Hospital das Clinicas. Instituto de Radiologia

    2017-03-15

    Objective: To evaluate the utility of the inspiratory phase in high-resolution computed tomography (HRCT) of the chest for the diagnosis of post-bone marrow transplantation bronchiolitis obliterans. Materials and Methods: This was a retrospective, observational, cross-sectional study. We selected patients of either gender who underwent bone marrow transplantation and chest HRCT between March 1, 2002 and December 12, 2014. Ages ranged from 3 months to 20.7 years. We included all examinations in which the HRCT was performed appropriately. The examinations were read by two radiologists, one with extensive experience in pediatric radiology and another in the third year of residency, who determined the presence or absence of the following imaging features: air trapping, bronchiectasis, alveolar opacities, nodules, and atelectasis. Results: A total of 222 examinations were evaluated (mean, 5.4 ± 4.5 examinations per patient). The expiratory phase findings were comparable to those obtained in the inspiratory phase, except in one patient, in whom a small uncharacteristic nodule was identified only in the inspiratory phase. Air trapping was identified in a larger number of scans in the expiratory phase than in the inspiratory phase, as was atelectasis, although the difference was statistically significant only for air trapping. Conclusion: In children being evaluated for post-bone marrow transplantation bronchiolitis obliterans, the inspiratory phase can be excluded from the chest HRCT protocol, thus reducing by half the radiation exposure in this population. (author)

  2. [Allogenic bone marrow transplantation versus autograft in acute lymphoblastic leukemia, in second remission in 113 children. Results of the Grupo Español de Transplante de Medula Niños (GETMON)].

    Science.gov (United States)

    Badell, I; Ortega, J J; Muñoz, A; Bureo, E; Madero, L; Olivé, T; Cubells, J; Maldonado, M S; Baro, J; Díaz, M A

    1996-04-01

    Using the data from the GETMON ("Grupo Español de Trasplante de Medula Osea en Niños") we carried out a retrospective analysis of the results of allogeneic bone marrow transplantation (alloBMT) compared to autologous bone marrow transplantation (ABMT) in 113 paediatric patients with acute lymphoblastic leukaemia (ALL) in second remission. Transplants were performed by the following centers, from April 1983 to December 1991: H. Vall d'Hebrón and H. Sant Pau from Barcelona, H. Ramón y Cajal and H. Niño Jesús from Madrid and H. Marqués de Valdecilla from Santander. The study included 113 patients between the ages of two and 16 years with ALL in second remission at marrow transplant. Fifty-six underwent alloBMT and 57 ABMT. Both groups were homogeneous with respect to age, sex, immunophenotype, duration of first remission, risk at diagnosis, percentage of early and late relapses, percentage with marrow or extramedullary relapse prior to transplant, time interval from attainment of second remission to transplant, and conditioning regimens applied for marrow transplant, with predominance of chemoradiotherapy in both. Haematologic recovery was observed to be faster in alloBMT than in ABMT. A granulocyte count > 0.5 x 10(9)/l was reached in alloBMT patients in a median of 19 days and in ABMT patients in a median of 25 days (p 30 months) 61.1 +/- 13.8%, than those who had presented an early relapse (< 30 months) 18.3 +/- 6.5% (p < 0.005). Probability of relapse was significantly greater in ABMT (70%) compared to alloBMT (46%) (p < 0.025). Transplant offers a better DFS in extramedullary relapses compared to isolated or combined bone marrow relapses: 71.4 +/- 17.1% with alloBMT and 38.1 +/- 14.7% with ABMT (p = NS). In our experience we observed a better DFS with alloBMT compared with ABMT, overcoat in early relapses, but without significant difference. A higher relapse rate in ABMT group is partially compensated by more early deaths in alloBMT offers a few survival

  3. Limitations and options using resorbable versus nonresorbable membranes for successful guided bone regeneration.

    Science.gov (United States)

    Soldatos, Nikolaos K; Stylianou, Popi; Koidou, Vasiliki P; Angelov, Nikola; Yukna, Raymond; Romanos, Georgios E

    2017-01-01

    Deficient bony ridges often complicate the implant treatment plan. Several treatment modalities are used to regenerate bone, including guided bone regeneration (GBR). The purpose of this study was to summarize the knowledge on different types of membranes available and currently used in GBR procedures in a staged approach or with simultaneous implant placement. The primary role of the membranes is to exclude epithelial and connective tissue cells from the wound area to be regenerated, and to create and maintain the space into which pluripotential and osteogenic cells are free to migrate. A literature search was performed for articles that were published in English on the topic. A selected number of studies were chosen in order to provide a review of the main characteristics, applications, and outcomes of the different types of membranes. Resorbable membranes are made of natural or synthetic polymers like collagen and aliphatic polyesters. Collagens are the most common type used. They have similar collagen composition to the periodontal connective tissue. Other materials available include human, porcine, and bovine pericardium membranes, human amnion and chorion tissue, and human acellular freeze-dried dermal matrix. Nonresorbable membranes used in GBR include dense-polytetrafluoroethylene (d-PTFE), expanded-polytetrafluoroethylene (e-PTFE), titanium mesh, and titanium-reinforced polytetrafluoroethylene. The most common complication of nonresorbable membranes is exposure, which has detrimental effect on the final outcome with both types of membranes. For vertical bone augmentation procedures, the most appropriate membranes are the nonresorbable. For combination defects, both types result in a successful outcome.

  4. Comparative alveolar ridge preservation using allogenous tooth graft versus free-dried bone allograft: A randomized, controlled, prospective, clinical pilot study

    Directory of Open Access Journals (Sweden)

    Chaitanya Pradeep Joshi

    2017-01-01

    Full Text Available Background: For the first time in India, allografts from human extracted teeth were prepared. A randomized, prospective, clinicoradiographical, histological study was conducted to evaluate their efficacy in comparison with freeze-dried bone allograft (FDBA in alveolar ridge preservation. Materials and Methods: Graft preparation: with written consent, teeth were collected from three donors (full mouth extraction cases. Once donors' serums were tested negative for HIV, HBV, HCV, and Venereal disease research laboratory (VDRL, mineralized whole tooth allograft (WTA and dentin allograft (DA were prepared using the standard protocol of Tissue Bank at Tata Memorial Hospital, Mumbai, India. Study Design: In this randomized controlled trial, 15 patients undergoing extraction of at least four teeth were selected. In each patient after atraumatic extractions, one socket was grafted with WTA, second with DA, third with FDBA, and fourth was left ungrafted (control site. All the sites were covered with chorion membrane. To estimate three-dimensional alveolar crest changes, cone beam computed tomography scans were taken immediately after grafting and 4 months postoperatively. Bone biopsies using 3 mm trephine bur were obtained from four patients at the time of implant placement and evaluated histologically. Results: Clinically uneventful healing was observed at all sites. Compared to other sites, WTA and DA consistently showed superior results demonstrating least reduction in alveolar crest height and width which was statistically significant (P < 0.05. Between WTA and DA sites, there was no statistically significant difference. Histological analysis also confirmed more new bone formation at WTA and DA sites. Conclusions: Rather than disposing extracted human teeth as a biomedical waste (common practice, they can be collected from suitable systemically healthy donors. With the help of tissue bank, they can be processed into an allograft, serving as an

  5. The immunodeficiency of bone marrow-transplanted patients. The effect of patient lymphocytes on the response of donor lymphocytes to mitogens and allogeneic cells

    DEFF Research Database (Denmark)

    Ødum, Niels; Hofmann, B; Platz, P

    1985-01-01

    -BMT lymphocytes were tested for functional suppressor activities against donor and recipient pre-BMT lymphocytes in the lymphocyte transformation test. None of these post-BMT cells suppressed the response of donor or pre-BMT cells to phytohaemagglutinin A or concanavalin A. In contrast, the response of donor......Lymphocytes from patients after bone marrow transplantation (BMT) are in most cases predominantly of the Leu-2+ (cytotoxic/suppressor) phenotypes and are almost unresponsive to mitogens. In contrast, normal Leu-3+-depleted, Leu-2+-enriched lymphocyte suspensions retain approximately 50......% of the mitogenic response compared with that of unseparated cells. To investigate whether this discrepancy was due to active suppression, we selected nine BMT patients from whom sufficient numbers of cells were available and whose lymphocyte phenotypes were predominantly Leu-2+ after BMT. These post...

  6. Reconstruction of beagle hemi-mandibular defects with allogenic mandibular scaffolds and autologous mesenchymal stem cells.

    Directory of Open Access Journals (Sweden)

    ChangKui Liu

    Full Text Available Massive bone allografts are frequently used in orthopedic reconstructive surgery, but carry a high failure rate of approximately 25%. We tested whether treatment of graft with mesenchymal stem cells (MSCs can increase the integration of massive allografts (hemi-mandible in a large animal model.Thirty beagle dogs received surgical left-sided hemi-mandibular defects, and then divided into two equal groups. Bony defects of the control group were reconstructed using allografts only. Those of the experimental group were reconstructed using allogenic mandibular scaffold-loaded autologous MSCs. Beagles from each group were killed at 4 (n = 4, 12 (n = 4, 24 (n = 4 or 48 weeks (n = 3 postoperatively. CT and micro-CT scans, histological analyses and the bone mineral density (BMD of transplants were used to evaluate defect reconstruction outcomes.Gross and CT examinations showed that the autologous bone grafts had healed in both groups. At 48 weeks, the allogenic mandibular scaffolds of the experimental group had been completely replaced by new bone, which has a smaller surface area to that of the original allogenic scaffold, whereas the scaffold in control dogs remained the same size as the original allogenic scaffold throughout. At 12 weeks, the BMD of the experimental group was significantly higher than the control group (p<0.05, and all micro-architectural parameters were significantly different between groups (p<0.05. Histological analyses showed almost all transplanted allogeneic bone was replaced by new bone, principally fibrous ossification, in the experimental group, which differed from the control group where little new bone formed.Our study demonstrated the feasibility of MSC-loaded allogenic mandibular scaffolds for the reconstruction of hemi-mandibular defects. Further studies are needed to test whether these results can be surpassed by the use of allogenic mandibular scaffolds loaded with a combination of MSCs and osteoinductive growth

  7. Success of long bone fracture healing in ancient Egypt: a paleoepidemiological study of the Giza Necropolis skeletons.

    Science.gov (United States)

    Erfan Zaki, Moushira

    2013-01-01

    Complications may provide information regarding the management of fractures in ancient populations. The aim of this study was to determine the rates of long-bone fractures and the proportion of misalignments as indicators of failed treatment or no treatment at all in skeletons from the Giza Necropolis dating to the Old Kingdom period (2700-2190 BC). We visually examined for fractures 2287 long bones of 204 adult skeletons (112 male and 92 female) and took x-rays of fractured bones in standard AP and ML views, so that we can analyse misalignments. Fractures were found in 45 of the 2287 examined long bones (1.97 %). Most of the fractures healed with good alignment, most likely as a result of successful treatment, and only three fractures showed misalignment.

  8. Successful bone marrow transplantation in a patient with Diamond-Blackfan anemia with co-existing Duchenne muscular dystrophy: a case report

    Directory of Open Access Journals (Sweden)

    Kaur Jasmeet

    2011-06-01

    Full Text Available Abstract Introduction Diamond-Blackfan anemia and Duchenne muscular dystrophy are two rare congenital anomalies. Both anomalies occurring in the same child is extremely rare. Allogeneic hematopoietic stem cell transplantation is a well-established therapy for Diamond-Blackfan anemia. However, in patients with Duchenne muscular dystrophy, stem cell therapy still remains experimental. Case presentation We report the case of a nine-year-old boy of north Indian descent with Diamond-Blackfan anemia and Duchenne muscular dystrophy who underwent successful allogeneic hematopoietic stem cell transplantation. He is transfusion-independent, and his Duchenne muscular dystrophy has shown no clinical deterioration over the past 45 months. His creatine phosphokinase levels have significantly decreased to 300 U/L from 14,000 U/L pre-transplant. The patient is 100% donor chimera in the hematopoietic system, and his muscle tissue has shown 8% to 10.4% cells of donor origin. Conclusion Our patient's Diamond-Blackfan anemia was cured by allogeneic hematopoietic stem cell transplantation. The interesting clinical observation of a possible benefit in Duchenne muscular dystrophy cannot be ruled out. However, further clinical follow-up with serial muscle biopsies and molecular studies are needed to establish this finding.

  9. Successful conservative management of symptomatic bilateral dorsal patellar defects presenting with cartilage involvement and bone marrow edema: MRI findings

    Energy Technology Data Exchange (ETDEWEB)

    Kwee, Thomas C. [University Medical Center Utrecht, Department of Radiology and Nuclear Medicine, Utrecht (Netherlands); Meander Medical Center, Department of Radiology, Amersfoort (Netherlands); Sonneveld, Heleen [Meander Medical Center, Department of Orthopaedics, Amersfoort (Netherlands); Nix, Maarten [Meander Medical Center, Department of Radiology, Amersfoort (Netherlands)

    2016-05-15

    The dorsal patellar defect is a relatively rare entity that involves the superolateral quadrant of the patella. It is usually considered to represent a delayed ossification process, although its exact origin remains unclear. Because of its usually innocuous nature and clinical course, invasive interventions are generally deemed unnecessary, although curretage has been successfully performed on symptomatic cases. This case report presents a rather unusual case of symptomatic bilateral dorsal patellar defects with cartilage involvement and widespread surrounding bone marrow edema as demonstrated by magnetic resonance imaging (MRI). Both cartilage involvement and bone marrow edema should be considered part of the spectrum of associated MRI findings that can be encountered in this entity. Furthermore, the presented case shows that symptomatic dorsal patellar defects can be treated conservatively with success and that (decrease of) pain symptoms are likely related to (decrease of) bone marrow edema. (orig.)

  10. Allogeneic transplantation in multiple myeloma

    OpenAIRE

    Majolino,Ignazio; Severino,Alessandro

    2009-01-01

    In this review the authors present a state of art tretment of multiple myeloma.High dose chemo-radiotherapy followed by autologous hematopoietic stem cell transplantation has been show to be superior a conventional chemotherapy and a double transplantation. The authors discuss too, the allogeneic transplantation with reduced intensity conditioning, allogeneic versus tandem autologous, results the patients long term outcome and a approach about the use of donor lymphocytes, anti thimocyte glob...

  11. Successful laparoscopic repair of a lumbar hernia occurring after iliac bone harvest.

    Science.gov (United States)

    Kawashita, Yujo; Iwata, Toru; Kanetaka, Kengo; Ono, Shinichiro; Matsuo, Mitsutoshi; Nagayoshi, Shigeki; Kanematsu, Takashi

    2010-02-01

    Many techniques have been described for the surgical repair of lumbar hernias, including primary repair, local tissue flaps, and conventional mesh repair. All these open techniques require a large incision plus extensive dissection to expose the hernia ring. This report presents a case of a recurrent lumbar hernia, which was successfully repaired using a laparoscopic approach. A 75-year-old female presented with a symptomatic right lumbar hernia, 1-year after an iliac bone harvest for knee surgery. Under general anesthesia, the patient was placed in a lateral decubitus position. A 3 trocar technique was used to do adhesiolysis of the surrounding tissues, to provide an ample working space to identify the hernia. A composix dual mesh (bard) was tailored so that it would overlap the defect with intermittent fixation by a spiral tacker (protac). No hernia recurrence occurred over 2 years after surgery. The laparoscopic approach has significant advantages for the repair a lumbar hernia: it enables the exact localization of the anatomic defect, and the mesh can be placed deep into the defect, thus allowing the intraabdominal pressure to hold it in position.

  12. Functional tooth restoration by allogeneic mesenchymal stem cell-based bio-root regeneration in swine.

    Science.gov (United States)

    Wei, Fulan; Song, Tieli; Ding, Gang; Xu, Junji; Liu, Yi; Liu, Dayong; Fan, Zhipeng; Zhang, Chunmei; Shi, Songtao; Wang, Songlin

    2013-06-15

    Our previous proof-of-concept study showed the feasibility of regenerating the dental stem cell-based bioengineered tooth root (bio-root) structure in a large animal model. Here, we used allogeneic dental mesenchymal stem cells to regenerate bio-root, and then installed a crown on the bio-root to restore tooth function. A root shape hydroxyapatite tricalcium phosphate scaffold containing dental pulp stem cells was covered by a Vc-induced periodontal ligament stem cell sheet and implanted into a newly generated jaw bone implant socket. Six months after implantation, a prefabricated porcelain crown was cemented to the implant and subjected to tooth function. Clinical, radiological, histological, ultrastructural, systemic immunological evaluations and mechanical properties were analyzed for dynamic changes in the bio-root structure. The regenerated bio-root exhibited characteristics of a normal tooth after 6 months of use, including dentinal tubule-like and functional periodontal ligament-like structures. No immunological response to the bio-roots was observed. We developed a standard stem cell procedure for bio-root regeneration to restore adult tooth function. This study is the first to successfully regenerate a functional bio-root structure for artificial crown restoration by using allogeneic dental stem cells and Vc-induced cell sheet, and assess the recipient immune response in a preclinical model.

  13. Retrospective success and survival rates of dental implants placed with simultaneous bone augmentation in partially edentulous patients.

    Science.gov (United States)

    Bazrafshan, Nima; Darby, Ivan

    2014-07-01

    The aim of this study was to assess the success and survival rate of dental implants placed with simultaneous hard tissue grafting. All patients treated in Royal Dental Hospital of Melbourne who had implant placement with and without guided bone regeneration (GBR) procedures were identified. Seventy-three attended a follow-up appointment. These patients were examined recording probing depth, bleeding on probing, plaque accumulation and radiographic bone loss by one examiner. Clinical and radiographic findings were compared in grafted and non-grafted groups and also analysed for years in function. Approximately 50% of implants were placed simultaneous guided bone regeneration technique. In the majority of cases, defects were filled by deproteinized bovine bone mineral and covered with collagen membrane. The range of time in function was 20-88 months with a mean 34.8 (±1.7). Seventy-nine per cent of the implants placed in anterior maxilla were placed with GBR, while only 18% in posterior mandible needed grafting procedure. The cumulative implant survival rates at the time of examination was 97.95% for both GBR and non-GBR group. The mean PPD, BOP, and Plaque index were not statistically significantly different in GBR vs. non-GBR groups two to seven years in function. However, bone loss is significantly less in GBR group 2-7 years after function. The overall success rate was around 90% after 2-7 years in function with the GBR group slightly less than the non-GBR group, but not statistically significant. For the subjects included in this retrospective study, the data demonstrate that GBR is a predictable procedure. The survival and success rates of the implants inserted with simultaneous GBR were similar, if slightly lower, to the non-grafted implants. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Successful treatment of pain in melorheostosis with zoledronate, with improvement on bone scintigraphy

    Science.gov (United States)

    Slimani, Samy; Nezzar, Adlen; Makhloufi, Hachemi

    2013-01-01

    Melorheostosis is a very rare sclerosing bone disorder that involves frequently one limb. It may be asymptomatic, but pain and limb deformity may occur and can be very debilitating. Different reports have indicated efficacy of bisphosphonates (pamidronate and etidronate) on symptoms. We report an adult patient with a very painful melorheostosis, who  improved after treatment with zoledronate, either on symptoms or on bone scans. PMID:23813581

  15. Successful control of Epstein-Barr virus (EBV)-infected cells by allogeneic nonmyeloablative stem cell transplantation in a patient with the lethal form of chronic active EBV infection.

    Science.gov (United States)

    Uehara, Taeko; Nakaseko, Chiaki; Hara, Satoru; Harima, Akane; Ejiri, Megumi; Yokota, Akira; Saito, Yasushi; Nishimura, Miki

    2004-08-01

    Chronic active Epstein-Barr virus infection (CAEBV) is a heterogeneous EBV-related disorder, ranging from mild/moderate forms to rapidly lethal disorders. The lethal form of CAEBV is characterized by multiple organ failure, hemophagocytic syndrome, and development of lymphomas. Allogeneic stem cell transplantation is considered as the only potentially curative treatment for the lethal form of CAEBV, but it is not always desirable because of the high incidence of regimen-related toxicities. A 17-year-old female with CAEBV, who was refractory to conventional therapies and considered to be unable to receive a myeloablative regimen because of multiple organ dysfunction, underwent allogeneic nonmyeloablative stem cell transplantation (allo-NST) before developing a hematological malignancy. She has been well without any signs of CAEBV for 27 months after allo-NST, and we confirmed that specific cytotoxic T lymphocyte activity against EBV was reconstituted. This outcome suggests that allo-NST can control CAEBV by reconstituting the host immunity against EBV. Copyright 2004 Wiley-Liss, Inc.

  16. Successful treatment of aggressive aneurysmal bone cyst of the pelvis with serial embolization.

    Science.gov (United States)

    Rossi, Giuseppe; Mavrogenis, Andreas F; Papagelopoulos, Panayiotis J; Rimondi, Eugenio; Ruggieri, Pietro

    2012-06-01

    Intralesional surgery is most commonly used for aneurysmal bone cysts. Rarely is en bloc resection used for active, aggressive, recurrent lesions and those located in expendable bones. However, persistence or recurrence of aneurysmal bone cysts is common. The clinical behavior of aneurysmal bone cysts is more aggressive in younger patients. Selective embolization is used as the primary treatment for aneurysmal bone cysts in surgically difficult anatomical locations and as an adjuvant to surgical treatment to reduce intraoperative blood loss and facilitate curettage.This article describes a 3-year-old boy with an aggressive aneurysmal bone cyst of the pelvis involving the right ischiopubic rami that achieved curative treatment with 3 embolizations with N-2-butyl-cyanoacrylate. Biopsy was diagnostic; however, the clinical course was misleading. Twenty days after the first embolization, despite complete occlusion of the feeding vessels, the patient experienced severe pain, increased size of the lesion, and lateral subluxation of the right hip. Based on the imaging and histological diagnosis, intralesional hemorrhage was assumed, and repeat embolization was performed. After the second embolization, the patient experienced perineal skin necrosis from normal vessel embolization; it was treated with wound dressing changes and healed uneventfully. A third embolization was performed because of a persistent lesion. Six years after treatment, the patient was symptom free, and imaging showed complete ossification of the cyst.Selective catheterization and occlusion of the feeding arteries with the appropriate embolic agent provide tumor devascularization, size reduction, pain relief, and induction of new bone formation. Multiple procedures are often necessary, and complications may occur. Copyright 2012, SLACK Incorporated.

  17. Invasive Pulmonary Aspergillosis in a Sickle Cell Patient Transplant Recipient: A Successful Treatment

    Directory of Open Access Journals (Sweden)

    Katia Paciaroni

    2015-08-01

    Full Text Available Sickle Cell Anaemia (SCA is the most common inherited blood disorder and is associated with severe morbidity and decreased survival. Allogeneic Haematopoietic Stem Cell Transplantation (HSCT is the only curative approach. Nevertheless the decision to perform a marrow transplant includes the risk of major complications  and mortality transplant related. The infections represent the main cause of mortality for SCA patients undergoing transplant. Invasive Pulmonary Aspergillosis (IPA is a devastating opportunistic infection and remains a significant cause of morbidity and mortality in HSCT recipients. Data regarding IPA in the setting of SCA are lacking. In the present report,  we describe a patient with SCA who developed IPA after allogeneic bone marrow transplant. The fungal infection was treated by systemic antifungal therapy in addition to the surgery, despite  mild chronic GVHD and with continuing immunosuppression therapy. This case shows that IPA occurring in bone marrow recipient with SCA can be successful treated

  18. Systematic analysis on the efficacy of bone enhancement methods used for success in dental implants

    Directory of Open Access Journals (Sweden)

    S Elakkiya

    2017-01-01

    Conclusion: Based on the available data in the current existing studies with a follow-up period of at least 3–5 years, it can be summarized that the autologous bone grafts can be preferred over allografts and xenografts for grafting implant sites since they are stable for at least 3–5 years.

  19. Aneurysmal bone cyst does not hinder the success of kidney transplantation. A case report.

    Science.gov (United States)

    Giordano, Mario; Caloro, Giorgia; Gaeta, Alberto; Vergori, Antonio; Santangelo, Luisa; Giordano, Paolo; Ruggieri, Pietro

    2015-03-01

    Uremic osteodystrophy is an expected complication in subjects with chronic renal insufficiency. It develops gradually and progressively already during the conservative treatment and then during the dialysis treatment. It can present a wide histopathological spectrum including typical alterations (from osteitis fibrosa to osteomalacia and/or mixed lesions) or, more rarely, isolated bone lesions indicative of a brown tumor of the bone. These conditions must be clearly identified in the pretransplant phase, especially if a bone lesion indicative of a pathological condition possibly evolving into a neoplasm is detected fortuitously. We report the case of a 19-yr-old boy with renal insufficiency and candidate for a pre-emptive renal transplantation from a living donor, in whom the diagnosis of ABC of the pubic symphysis - asymptomatic and fortuitously detected while performing instrumental investigations - was suspected through the imaging studies (CT scan, MRI) and was confirmed by the histological examination. This made it possible to perform the renal transplant. The immunosuppressive treatment, which was subsequently administered, was based on steroids, calcineurin inhibitors (tacrolimus), and mycophenolate and did not determine any modification in the radiological aspect of the bone lesion, even after more than one yr from the transplant. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Successful treatment with ganciclovir of presumed Epstein-Barr meningo-encephalitis following bone marrow transplant

    NARCIS (Netherlands)

    Dellemijn, P L; Brandenburg, A; Niesters, H G; van den Bent, M J; Rothbarth, P H; Vlasveld, L T

    Epstein-Barr virus-specific polymerase chain reaction was used to diagnose EBV-meningo-encephalitis in a bone marrow transplant recipient. The patient made complete recovery with ganciclovir treatment. Pitfalls in diagnosis with EBV-PCR and the potential therapeutic efficacy of ganciclovir in EBV

  1. Potential Use of Bacterial Community Succession in Decaying Human Bone for Estimating Postmortem Interval.

    Science.gov (United States)

    Damann, Franklin E; Williams, Daniel E; Layton, Alice C

    2015-07-01

    Bacteria are taphonomic agents of human decomposition, potentially useful for estimating postmortem interval (PMI) in late-stage decomposition. Bone samples from 12 individuals and three soil samples were analyzed to assess the effects of decomposition and advancing time on bacterial communities. Results indicated that partially skeletonized remains maintained a presence of bacteria associated with the human gut, whereas bacterial composition of dry skeletal remains maintained a community profile similar to soil communities. Variation in the UniFrac distances was significantly greater between groups than within groups (p decomposition stages. The oligotrophic environment of bone relative to soft tissue and the physical protection of organic substrates may preclude bacterial blooms during the first years of skeletonization. Therefore, community membership (unweighted) may be better for estimating PMI from skeletonized remains than community structure (weighted). © 2015 American Academy of Forensic Sciences.

  2. O transplante de medula óssea na leucemia mielóide aguda: análise de 80 pacientes transplantados no complexo do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo The allogeneic and autologous bone marrow transplantation in acute myeloid leukemia: analysis of 80 patients - Bone Marrow Transplantation Service - Hospital das Clínicas of the Medical School, University of São Paulo

    Directory of Open Access Journals (Sweden)

    Nadjanara D. Bueno

    2004-01-01

    Full Text Available Oitenta pacientes consecutivos portadores de Leucemia Mielóide Aguda (LMA submetidos a transplante de medula óssea alogênico (TMO alo e autogênico (TMO auto, foram selecionados entre 1989 e 2001. Quarenta por cento dos mesmos estavam vivos ao final do estudo; no TMO alo 37,9% e no TMO auto 45,4%. Fatores como sexo, classificação Franco-Americano-Britânica de LMA, tratamento de indução, número de células infundidas e regime de condicionamentos não tiveram significância estatística na sobrevida. Pacientes portadores de LMA M1 a M4 e que foram submetidos à consolidação com altas doses de arabinosídeo tiveram melhor sobrevida (p= 0,0148. Pacientes em 1º remissão completa se beneficiaram com TMO alo e auto, com uma sobrevida de 52,6% e 69,2% respectivamente. A presença de doença enxerto contra o hospedeiro (DECH aguda teve impacto na sobrevida dos pacientes quando se comparou ausência de DECH aguda, grau I/II com III/IV (p= 0,0285. Infecção foi a causa de óbito mais freqüente no TMO alo. No TMO auto, a recidiva foi a principal causa de óbito. Morte por toxicidade relacionada ao procedimento ocorreu em 38,9% dos pacientes que morreram no TMO alo e em 16,7% no TMO auto. Na análise univariada de Cox para fatores prognósticos, tiveram significância a fase da doença e a DECH aguda, que perderam significância na análise multivariada (p=0,069.The patients records of eighty consecutive patients with acute myeloid leukemia (AML submitted to allogeneic (allo BMT and autologous (auto BMT bone marrow transplantation (BMT between 1989 and 2001 were assessed. Forty percent were alive in the end of the study; 37.9% of allogeneic patients and 45.4% of autologous. Factors such as gender, the French-American-British AML classification, induction treatment, number of infused cells and the conditioning regiment did not have any impact in survival. Patients with AML from M1 to M4, and who were consolidated with high doses of arabinoside

  3. Successful treatment of perineal necrotising fasciitis and associated pubic bone osteomyelitis with the vacuum assisted closure system

    Science.gov (United States)

    Kumar, Susim; O'Donnell, Mark E; Khan, Khalid; Dunne, Gillian; Carey, P Declan; Lee, Jack

    2008-01-01

    Background Acute necrotising fasciitis is a life-threatening condition, which requires urgent surgical intervention. Surgical debridement is invariably associated with large areas of tissue loss. Case presentation We present a 58-year old woman with a past history of cervical carcinoma who presented with necrotising fasciitis of the perineum and upper thighs with associated pubic bone osteomyelitis. Following extensive debridement, a Vacuum Assisted Closure (VAC) system was applied to the large residual defect to facilitate skin graft application and optimise wound healing. Conclusion This case demonstrates the successful management of a complex and potentially lethal wound of the perineum with debridement, skin grafting and the VAC system. PMID:18577204

  4. Successful treatment of perineal necrotising fasciitis and associated pubic bone osteomyelitis with the vacuum assisted closure system

    Directory of Open Access Journals (Sweden)

    Dunne Gillian

    2008-06-01

    Full Text Available Abstract Background Acute necrotising fasciitis is a life-threatening condition, which requires urgent surgical intervention. Surgical debridement is invariably associated with large areas of tissue loss. Case presentation We present a 58-year old woman with a past history of cervical carcinoma who presented with necrotising fasciitis of the perineum and upper thighs with associated pubic bone osteomyelitis. Following extensive debridement, a Vacuum Assisted Closure (VAC system was applied to the large residual defect to facilitate skin graft application and optimise wound healing. Conclusion This case demonstrates the successful management of a complex and potentially lethal wound of the perineum with debridement, skin grafting and the VAC system.

  5. Successful Treatment of Fanconi Anemia and T-Cell Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Terrie Flatt

    2012-01-01

    Full Text Available Fanconi anemia is associated with an increased risk of malignancy. Patients are sensitive to the toxic effects of chemotherapy. We report the case of a patient with Fanconi anemia who developed T-cell acute lymphoblastic leukemia. He experienced chemotherapy-related complications including prolonged neutropenia, grade IV vincristine neuropathy, and disseminated aspergillosis. He was successfully treated with modified dosing of cytarabine and intrathecal methotrexate followed by allogeneic bone marrow transplant. The aspergillosis was treated with systemic antifungal treatment and surgical resection. Now 30 months after bone marrow transplant the patient is without evidence of aspergillosis or leukemia.

  6. Differential diagnosis of skin lesions after allogeneic haematopoietic stem cell transplantation

    NARCIS (Netherlands)

    Canninga-van Dijk, MR; Sanders, CJ; Verdonck, LF; Fijnheer, R; van den Tweel, JG

    Allogeneic haematopoietic stem cell transplantation (i.e. bone marrow or peripheral blood stem cell transplantation) is a common procedure in the treatment of various haematological disorders such as aplastic anaemia, (pre)leukaemias, some malignant lymphomas, multiple myeloma and immunodeficiency

  7. Gut microbiota and allogeneic transplantation.

    Science.gov (United States)

    Wang, Weilin; Xu, Shaoyan; Ren, Zhigang; Jiang, Jianwen; Zheng, Shusen

    2015-08-23

    The latest high-throughput sequencing technologies show that there are more than 1000 types of microbiota in the human gut. These microbes are not only important to maintain human health, but also closely related to the occurrence and development of various diseases. With the development of transplantation technologies, allogeneic transplantation has become an effective therapy for a variety of end-stage diseases. However, complications after transplantation still restrict its further development. Post-transplantation complications are closely associated with a host's immune system. There is also an interaction between a person's gut microbiota and immune system. Recently, animal and human studies have shown that gut microbial populations and diversity are altered after allogeneic transplantations, such as liver transplantation (LT), small bowel transplantation (SBT), kidney transplantation (KT) and hematopoietic stem cell transplantation (HTCT). Moreover, when complications, such as infection, rejection and graft versus host disease (GVHD) occur, gut microbial populations and diversity present a significant dysbiosis. Several animal and clinical studies have demonstrated that taking probiotics and prebiotics can effectively regulate gut microbiota and reduce the incidence of complications after transplantation. However, the role of intestinal decontamination in allogeneic transplantation is controversial. This paper reviews gut microbial status after transplantation and its relationship with complications. The role of intervention methods, including antibiotics, probiotics and prebiotics, in complications after transplantation are also discussed. Further research in this new field needs to determine the definite relationship between gut microbial dysbiosis and complications after transplantation. Additionally, further research examining gut microbial intervention methods to ameliorate complications after transplantation is warranted. A better understanding of the

  8. Diffuse hemorrhagic colitis in a patient with dyskeratosis congenita after nonmyeloablative allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Ehlert, Karoline; Rossig, Claudia; Groll, Andreas H; Beyna, Torsten; Froehlich, Birgit; Juergens, Heribert

    2015-01-01

    Dyskeratosis congenita (DC) is a rare inherited disorder characterized by reticular skin pigmentation, oral cavity leukoplakia, and nail dystrophy. Bone marrow failure in DC can only be cured by allogeneic hematopoietic stem cell transplantation (HSCT). After a nonmyeloablative, matched unrelated donor transplant, the 21-year-old patient experienced severe lower gastrointestinal tract hemorrhage caused by diffuse colitis. The etiology remained unclear. Diffuse colitis with life-threatening hemorrhage has now been reported in 3 DC patients after unrelated allogeneic HSCT. To identify the underlying causes and the disease-specific risks, and to allow for prevention and/or optimal management, data should be prospectively collected.

  9. Mixed allogeneic reconstitution (A+B----A) to induce donor-specific transplantation tolerance. Permanent acceptance of a simultaneous donor skin graft

    Energy Technology Data Exchange (ETDEWEB)

    Ildstad, S.T.; Wren, S.M.; Oh, E.; Hronakes, M.L. (Department of Surgery, University of Pittsburgh, Pennsylvania (USA))

    1991-06-01

    Mixed allogeneic reconstitution, in which a mixture of T-cell-depleted bone marrow of syngeneic host and allogeneic donor type is transplanted into a lethally irradiated recipient (A+B----A), results in mixed lymphopoietic chimerism with engraftment of a mixture of both host and donor bone marrow elements. Recipients are specifically tolerant to donor both in vitro and in vivo. Donor-specific skin grafts survive indefinitely when they are placed after full bone marrow repopulation at 28 days, while third-party grafts are rapidly rejected. To determine whether a delay of a month or more for full bone marrow repopulation is required before a donor-specific graft can be placed, we have now examined whether tolerance induction can be achieved if a graft is placed at the time of bone marrow transplantation. Permanent acceptance of donor-specific B10.BR skin grafts occurred when mixed allogeneic chimerism (B10+B10.BR----B10) was induced and a simultaneous allogeneic donor graft placed. In vitro, mixed reconstituted recipients were specifically tolerant to the B10.BR donor lymphoid cells but fully reactive to MHC-disparate third-party (BALB/c; H-2dd) when assessed by mixed lymphocyte reaction (MLR) and cell-mediated lympholysis (CML) assays. These data therefore indicate that a donor-specific graft placed at the time of mixed allogeneic reconstitution is permanently accepted without rejection. To determine whether an allogeneic skin graft alone without allogeneic bone marrow would be sufficient to induce tolerance, syngeneic reconstitution (B10----B10) was carried out, and a simultaneous B10.BR allogeneic skin graft placed. Although skin grafts were prolonged in all recipients, all grafts rejected when full lymphopoietic repopulation occurred at 28 days.

  10. Iodoacetate and allogenous cartilage particles as models for arthritis induction in equine

    Directory of Open Access Journals (Sweden)

    Ahmed Elmesiry

    2014-12-01

    Full Text Available Experimental models of osteoarthritis (OA have been widely developed in different animal species, because of the high incidence of osteoarthritis diseases in humans and animals. To date, no ideal OA animal model has been reported. The present study compare different osteoarthritis models to determine which one is suitable for inducing experimental equine OA. Fifteen donkeys were divided into three equal groups (n = 5. The radio carpal joints of the right forelimb of 15 donkeys were injected with 25 mg monoiodoacetate (MIA (group A, 50 mg allogenous cartilage particles (ACP (group B, or vehicle solution (group C over a period of 70 days. Osteoarthritis induction was evaluated weekly through lameness score, carpal circumference, joint flexion angel, synovial fluid analysis (total protein and WBC count, and radiology. Animal were euthanized and joints histopathology were performed at 70 days. Lameness score and joint circumference was increased in both group A and B however joint flexion angel was decreased compared to group C (p < 0.05. Osteophytes were observed in MIA injected joints only accompanied with subchondral bone sclerosis. Cartilage damage was observed grossly and histologically in Group A together with synovial membrane fibrosis. Group B had on cartilage damage grossly however histological examination revealed some cartilage surface discontinuity with synovial membrane edema. Injection of monoiodoacetate in the donkey is a successful model to create the acute clinical signs of joint disease as well as cartilage damage. However, allogenous cartilage particles injection need more investigation to be applied.

  11. Kidney dysfunction after allogeneic stem cell transplantation

    NARCIS (Netherlands)

    Kersting, S.

    2008-01-01

    Allogeneic stem cell transplantation (SCT) is a widely accepted approach for malignant and nonmalignant hematopoietic diseases. Unfortunately complications can occur because of the treatment, leading to treatment-related mortality. We studied kidney dysfunction after allogeneic SCT in 2 cohorts of

  12. Evaluation of safety and efficacy of radiation-sterilized bone allografts in reconstructive oral surgery

    OpenAIRE

    Krasny, Marta; Krasny, Kornel; Kami?ski, Artur; Zadurska, Ma?gorzata; Piekarczyk, Piotr; Fiedor, Piotr

    2012-01-01

    Bone grafting allows reconstruction of the atrophied or destroyed alveolar process. In orthopaedics and traumatology allogeneic grafting has been used to restore defects of osseous tissue for over 60?years. In order to improve safety of the graft recipient, sterilized allogeneic grafts have been use. The aim of the study was to assess the direct and long-term outcomes following augmentation of atrophied alveolar processes with the use of radiation-sterilized allogeneic bone grafts. Sixty-eigh...

  13. Elastomeric enriched biodegradable polyurethane sponges for critical bone defects: a successful case study reducing donor site morbidity.

    Science.gov (United States)

    Lavrador, Catarina; Mascarenhas, Ramiro; Coelho, Paulo; Brites, Cláudia; Pereira, Alfredo; Gogolewski, Sylwester

    2016-03-01

    Bone substitutes have been a critical issue as the natural source can seldom provide enough bone to support full healing. No bone substitute complies with all necessary functions and characteristics that an autograft does. Polyurethane sponges have been used as a surgical alternative to cancellous bone grafts for critical bone defect donor sites. Critical bone defects were created on the tibial tuberosity and iliac crest using an ovine model. In group I (control-untreated), no bone regeneration was observed in any animal. In group II (defects left empty but covered with a microporous polymeric membrane), the new bone bridged the top ends in all animals. In groups III and IV, bone defects were implanted with polyurethane scaffolds modified with biologically active compounds, and bone regeneration was more efficient than in group II. In groups III and IV there were higher values of bone regeneration specific parameters used for evaluation (P substances may offer an alternative to bone graft, reducing donor site morbidity associated with autogenous cancellous bone harvesting.

  14. Bone mineral density improvement after successful parathyroidectomy in pre- and postmenopausal women with primary hyperparathyroidism: a prospective study.

    Science.gov (United States)

    Lumachi, Franco; Camozzi, Valentina; Ermani, Mario; DE Lotto, Federica; Luisetto, Giovanni

    2007-11-01

    The aim of this study was to evaluate the short-term (1 year) changes of the lumbar spine (L2-L4) bone mineral density (LS-BMD) after parathyroidectomy (PTx) in pre- and postmenopausal women with primary hyperparathyroidism (PHPT). A series of 48 women (median age 56 years, range 23-82 years) with confirmed PHPT were prospectively enrolled in the study. Patients who received both oral contraceptives less than 2 years before the diagnosis and estrogen replacement therapy have previously been excluded. All patients underwent LS-BMD by dual energy x-ray absorptiometry before surgery. Patients were divided into two groups: group A (n = 12) premenopausal, and group B (n = 36) postmenopausal patients. The LS-BMD was repeated 12 months after successful PTx. Basal LS-BMD (0.852 +/- 0.061 vs. 0.748 +/- 0.142 g/cm(2)), serum calcium (2.95 +/- 0.23 vs. 2.94 +/- 0.26 mmol/L), creatinine (69.2 +/- 17.5 vs. 82.0 +/- 24.2 micromol/L), alkaline phosphatase (107.4 +/- 43.6 vs. 151.3 +/- 95.7 U/L), osteocalcin (28.6 +/- 9.3 vs. 28.2 +/- 8.3 microg/L), and PTH (192.7 +/- 133.2 vs. 175.2 +/- 132.1 ng/L) levels did not differ significantly (P = NS) between groups. The 1-year LS-BMD was 0.921 +/- 0.048 and 0.825 +/- 0.151 g/cm(2) in group A and B, respectively. In group B patients, the 1-year LS-BMD value did not improve significantly (P = NS), while in group A patients the difference between basal and postsurgical LS-BMD was significant (P < 0.01). In conclusion, PTx should be considered for all patients with PHPT and loss of bone density, but in premenopausal patients a greatest improvement of BMD may be found, suggesting the need of endogenous estrogens in complete lumbar bone recovery after surgery.

  15. Localized ridge augmentation with allogenic block grafts prior to implant placement: case reports and histologic evaluations.

    Science.gov (United States)

    Petrungaro, Paul S; Amar, Salomon

    2005-06-01

    The placement of dental implants is based on the amount of alveolar bone present in the edentulous site to be reconstructed. Insufficient alveolar contours may require bone grafting procedures to restore an adequate bone volume before implant placement. Larger osseous defects often require block grafts harvested from the symphysis or the ramus buccal shelf region. These provide adequate donor sites to harvest a graft sufficient to restore a significant defect in the osseous structures planned for implant placements. Autogenous block grafts have been well established to reconstruct these types of defects prior to implant placement procedures. However, surgical complications associated with the unfavorable anatomical structures and the necessity of large donor sites (e.g., symphysis and ramus buccal shelf) have led to the use of allogenic grafting materials. Recent developments in allogenic grafting materials have lead to the development of a corticocancellous block graft harvested from the iliac crest region. This study evaluates the clinical indications of these allogenic graft materials to replace compromised alveolar bone defects both horizontal and vertical in nature. The analysis is supported by re-entry procedures and histologic evaluations to substantiate predictability.

  16. RENAL ALLOGENEIC TRANSPLANTATION IN PATIENT WITH HAEMOPHILIA B

    Directory of Open Access Journals (Sweden)

    N. V. Purlo

    2014-01-01

    Full Text Available We report the case of successful renal allogeneic transplantation and treatment in a 56-year-old patient with haemophilia B at Hematology Research Center. He has received replacement therapy by factor IX since 2010. The transplant is marked with good renal function during 13 post-transplant months without episodes of rejection or bleeding complications. The complicated surgical interventions are possible in patients with haemophilia В аnd end-stage chronic renal failure in the presence of replacement therapy of IX factor for the purpose of achievement of optimum hemostasis.

  17. Successful treatment of chronic osteomyelitis in children with debridement, antibiotic-laden cement spacer and bone graft substitute.

    Science.gov (United States)

    Canavese, Federico; Corradin, Marco; Khan, Ahmad; Mansour, Mounira; Rousset, Marie; Samba, Antoine

    2017-02-01

    Chronic osteomyelitis and infected nonunion are relatively rare conditions in pediatric patients and are more frequently seen in developing countries. Although relatively rare, they are medically and surgically challenging. Here we report a novel surgical technique used to manage five patients with chronic osteomyelitis of long bones. Five skeletally immature patients with chronic osteomyelitis and infected nonunion of the long bones were treated surgically between 2010 and 2014 by a combination of resection of necrotic infected bone, debridement of surrounding soft tissue, and application of antibiotic-laden cement spacer inducing periosteal membrane before final bone reconstruction. Once inflammatory markers normalized, all the patients were re-operated for cement removal, bone graft substitution, and concomitant osteosynthesis of the affected bone, if needed. All patients underwent MRI, CT scan, and laboratory evaluation prior to surgery. The antibiotic regimen was started empirically and then adjusted according to culture and sensitivity results. Mean patient age at the time of diagnosis was 11 years (range 4-14), and all patients had at least 2-year follow-up (range 2-5). At last follow-up, clinical and laboratory evaluation had normalized, the bone had healed, and all patients had resumed daily living and sports activities. Surgical debridement is the standard approach to chronic osteomyelitis. Use of antibiotic-laden cement is recommended to penetrate local infection, with antibiotic therapy playing an adjunctive role. The cement also induces membrane formation that aids bone reconstruction. IV.

  18. Successful use of autogenous bone graft for the treatment of a radius-ulna nonunion in an amputee dog

    Directory of Open Access Journals (Sweden)

    B.W. Minto

    2015-08-01

    Full Text Available Fracture nonunions represent important complications in orthopedic surgeries. Nonunion repairs or bone defects are surgically challenging. Our aim was to describe a nonunion case, which was repaired with rapid bone recovery. An 8-month-old male mixed breed dog that has been previously operated was presented to the Veterinary Medical Teaching Hospital of São Paulo State University, with a right radius-ulna nonunion and an amputated contralateral forelimb. A cancellous bone graft was collected from a partially amputated limb, in order to correct the nonunion, and used in association with a locking plate. After four weeks, the bone graft had been incorporated into the original bone. Clinical union with good weight bearing was achieved after eight weeks.

  19. Allogeneic Mesenchymal Stem Cells in Combination with Hyaluronic Acid for the Treatment of Osteoarthritis in Rabbits.

    Directory of Open Access Journals (Sweden)

    En-Rung Chiang

    Full Text Available Mesenchymal stem cell (MSC-based therapies may aid in the repair of articular cartilage defects. The purpose of this study was to investigate the effects of intraarticular injection of allogeneic MSCs in an in vivo anterior cruciate ligament transection (ACLT model of osteoarthritis in rabbits. Allogeneic bone marrow-derived MSCs were isolated and cultured under hypoxia (1% O2. After 8 weeks following ACLT, MSCs suspended in hyaluronic acid (HA were injected into the knees, and the contralateral knees were injected with HA alone. Additional controls consisted of a sham operation group as well as an untreated osteoarthritis group. The tissues were analyzed by macroscopic examination as well as histologic and immunohistochemical methods at 6 and 12 weeks post-transplantation. At 6 and 12 weeks, the joint surface showed less cartilage loss and surface abrasion after MSC injection as compared to the tissues receiving HA injection alone. Significantly better histological scores and cartilage content were observed with the MSC transplantation. Furthermore, engraftment of allogenic MSCs were evident in surface cartilage. Thus, injection of the allogeneic MSCs reduced the progression of osteoarthritis in vivo.

  20. Allogeneic Mesenchymal Stem Cells in Combination with Hyaluronic Acid for the Treatment of Osteoarthritis in Rabbits.

    Science.gov (United States)

    Chiang, En-Rung; Ma, Hsiao-Li; Wang, Jung-Pan; Liu, Chien-Lin; Chen, Tain-Hsiung; Hung, Shih-Chieh

    2016-01-01

    Mesenchymal stem cell (MSC)-based therapies may aid in the repair of articular cartilage defects. The purpose of this study was to investigate the effects of intraarticular injection of allogeneic MSCs in an in vivo anterior cruciate ligament transection (ACLT) model of osteoarthritis in rabbits. Allogeneic bone marrow-derived MSCs were isolated and cultured under hypoxia (1% O2). After 8 weeks following ACLT, MSCs suspended in hyaluronic acid (HA) were injected into the knees, and the contralateral knees were injected with HA alone. Additional controls consisted of a sham operation group as well as an untreated osteoarthritis group. The tissues were analyzed by macroscopic examination as well as histologic and immunohistochemical methods at 6 and 12 weeks post-transplantation. At 6 and 12 weeks, the joint surface showed less cartilage loss and surface abrasion after MSC injection as compared to the tissues receiving HA injection alone. Significantly better histological scores and cartilage content were observed with the MSC transplantation. Furthermore, engraftment of allogenic MSCs were evident in surface cartilage. Thus, injection of the allogeneic MSCs reduced the progression of osteoarthritis in vivo.

  1. Pulpal regeneration following allogenic tooth transplantation into mouse maxilla.

    Science.gov (United States)

    Unno, Hideki; Suzuki, Hironobu; Nakakura-Ohshima, Kuniko; Jung, Han-Sung; Ohshima, Hayato

    2009-04-01

    Autogenic tooth transplantation is now a common procedure in dentistry for replacing a missing tooth. However, there are many difficulties in clinical application of allogenic tooth transplantation because of immunological rejection. This study aims to clarify pulpal regeneration following allogenic tooth transplantation into the mouse maxilla by immunohistochemistry for 5-bromo-2'-deoxyuridine (BrdU) and nestin, and by the histochemistry for tartrate-resistant acid phosphatase (TRAP). The upper right first molar (M1) of 2-week-old mice was extracted and allografted in the original socket in both the littermate and non-littermate after the extraction of M1. Tooth transplantation weakened the nestin-positive reactions in the pulp tissue that had shown immunoreactivity for nestin before operation. On postoperative Days 5-7, tertiary dentin formation commenced next to the preexisting dentin where nestin-positive odontoblast-like cells were arranged in all cases of the littermate group until Day 14, except for one case showing immunological rejection in the pulp chamber. In the non-littermate group, bone-like tissue formation occurred in the pulp chamber in addition to tertiary dentin formation until Day 14. The rate of tertiary dentin was 38%, and the rate of the mixed form of dentin and bone-like tissue formation was 23% (the remainder was immunological rejection). Interestingly, the periodontal tissue recovered even in the case of immunological rejection in which the pulp chamber was replaced by sparse connective tissue. These results suggest that the selection of littermate or non-littermate is decisive for the survival of odontoblast-lineage cells and that the immunological rejection does not influence the periodontal regeneration.

  2. IL-22 promoted CD3+ T cell infiltration by IL-22R induced STAT3 phosphorylation in murine acute graft versus host disease target organs after allogeneic bone marrow transplantation.

    Science.gov (United States)

    Zhao, Kai; Ruan, Suhong; Tian, Yu; Zhao, Dongmei; Chen, Chong; Pan, Bin; Yan, Zhiling; Yin, Lingling; Zhu, Shengyun; Xu, Kailin

    2016-10-01

    Graft versus host disease (GVHD) is a life threatening complication of bone marrow stem cell transplantation, in which considerable numbers of proinflammatory cytokines secreted by allo-reactive donor T cells are involved. We and other previous studies have found that interleukin-22 (IL-22) was able to aggravate the target organs damage of GVHD. However, the mechanism and the signal pathway of IL-22 in murine acute GVHD was not clear. Here, we observed that compared with GVHD group, more serious pathological damage and more CD3(+) T cells infiltrated in GVHD target organs were detected in the mice injected with IL-22. Meanwhile, transcription factor T-bet, RORγt and AhR respectively associated with Th1, Th17 and Th22 cells changed in varying degrees in different GVHD target organs. Furthermore, the increased expression of IL-22R and its downstream protein P-STAT3 were detected in GVHD mice with IL-22 treated. These results suggested that the pathological role of IL-22 in GVHD target organs contribute to exogenous injected IL-22 as well as secreted IL-22 from the infiltrated allo-reactive effector T cells. In addition, the IL-22R-STAT3 pathway may play important role in GVHD tissue injury and target this way may yield new approaches for reduction of GVHD. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Demineralized bone matrix and human cancellous bone enhance fixation of porous-coated titanium implants in sheep

    DEFF Research Database (Denmark)

    Babiker, Hassan; Ding, Ming; Overgaard, Søren

    2016-01-01

    Allogenic bone graft has been considered the gold standard in connection with bone graft material in revision joint arthroplasty. However, the lack of osteogenic potential and the risk of disease transmission are clinical challenges. The use of osteoinductive materials, such as demineralized bone...

  4. A rare case report of peri-implant bone necrosis: Mapping the distance of initial peri-implant complication toward a path of success

    Directory of Open Access Journals (Sweden)

    S K Salaria

    2011-01-01

    Full Text Available In the past decade, science of implant placement has greatly advanced and at the same time much success has been experienced with the endosseous implant. Despite the long-term predictability of the implants, however, biological, technical and esthetic complications do occur. The use of osseointegrated implants as a foundation for prosthetic replacement of missing teeth has been highly predictable, but still at present, there is no consensus of how to best manage the complications occurring after implant placement. In this report, we discuss post-insertion complication of bone necrosis and its successful management.

  5. Differentiation of allogeneic mesenchymal stem cells induces immunogenicity and limits their long-term benefits for myocardial repair.

    Science.gov (United States)

    Huang, Xi-Ping; Sun, Zhuo; Miyagi, Yasuo; McDonald Kinkaid, Heather; Zhang, Li; Weisel, Richard D; Li, Ren-Ke

    2010-12-07

    Cardiac cell therapy for older patients who experience a myocardial infarction may require highly regenerative cells from young, healthy (allogeneic) donors. Bone marrow mesenchymal stem cells (MSCs) are currently under clinical investigation because they can induce cardiac repair and may also be immunoprivileged (suitable for allogeneic applications). However, it is unclear whether allogeneic MSCs retain their immunoprivilege or functional efficacy late after myocardial implantation. We evaluated the effects of MSC differentiation on the immune characteristics of cells in vitro and in vivo and monitored cardiac function for 6 months after post-myocardial infarction MSC therapy. In the in vitro experiments, inducing MSCs to acquire myogenic, endothelial, or smooth muscle characteristics (via 5-azacytidine or cytokine treatment) increased major histocompatibility complex-Ia and -II (immunogenic) expression and reduced major histocompatibility complex-Ib (immunosuppressive) expression, in association with increased cytotoxicity in coculture with allogeneic leukocytes. In the in vivo experiments, we implanted allogeneic or syngeneic MSCs into infarcted rat myocardia. We measured cell differentiation and survival (immunohistochemistry, real-time polymerase chain reaction) and cardiac function (echocardiography, pressure-volume catheter) for 6 months. MSCs (versus media) significantly improved ventricular function for at least 3 months after implantation. Allogeneic (but not syngeneic) cells were eliminated from the heart by 5 weeks after implantation, and their functional benefits were lost within 5 months. The long-term ability of allogeneic MSCs to preserve function in the infarcted heart is limited by a biphasic immune response whereby they transition from an immunoprivileged to an immunogenic state after differentiation, which is associated with an alteration in major histocompatibility complex-immune antigen profile.

  6. Tratamento da recidiva da leucemia mielóide crônica após transplante de medula óssea alogênico utilizando mesilato de imatinibe: relato de três casos Treatment of chronic myelogenous leukemia relapse after allogeneic bone marrow transplantation with imatinib mesylate: report of three cases

    Directory of Open Access Journals (Sweden)

    Ronald Pallotta

    2006-06-01

    Full Text Available O mesilato de imatinibe (MI, inibidor seletivo da tirosinoquinase envolvido na patogênese da leucemia mielóide crônica (LMC, tem se constituído como terapia farmacológica de primeira linha para o tratamento desta doença. A infusão de linfócitos do doador (DLI tem sido considerada como tratamento padrão para recidiva da LMC após transplante de medula óssea (TMO alogênico, apesar de estar freqüentemente associado à ocorrência de doença do enxerto contra hospedeiro e mielossupressão. Por apresentar resultados satisfatórios e boa tolerabilidade no tratamento da LMC, os autores empregaram o mesilato de imatinib como terapêutica alternativa à DLI em pacientes que sofreram recidiva após o TMO. Obtiveram sucesso em dois casos, sendo que em um houve retorno comprovado do quimerismo do doador. No terceiro caso houve progressão da doença e o paciente foi encaminhado para segundo TMO. Desta forma, devido ao caráter recente do tema, este estudo descritivo sugere que esta opção terapêutica possa ser estudada como alternativa na recaída pós-TMO.Imatinib mesylate (MI, a selective tyrosine kinase inhibitor involved in the pathogenesis of chronic myelogenous leukemia (CML, has become the first-line treatment for this disease. Donor lymphocyte infusion (DLI has been considered as the standard treatment for relapse after allogeneic bone marrow transplantation (BMT, even though it is frequently associated with graft versus host disease and myelosuppression. Because of the satisfactory results and tolerance of the treatment of CML, the authors used MI as an alternative therapy for DLI in patients that relapsed after BMT. They obtained cytogenetic remission in two cases, with, in one case, proven conversion to the donor chimera. The third case evolved with progression of the disease and a second BMT was required. Since this is a new alternative, this descriptive study suggests it should be considered as an alternative therapy for relapse

  7. Menopause and Bone Loss

    Science.gov (United States)

    ... up bone loss. After menopause your ovaries stop producing the hormone estrogen, which helps to keep your ... you minimize and treat bone loss? Diet and lifestyle can help prevent and treat bone loss. Successful ...

  8. [The bone bank--a standardized procedure? Results of a federal survey of German surgical clinics].

    Science.gov (United States)

    Knaepler, H; Laubach, S; Gotzen, L

    1990-11-01

    An inquiry at German surgical departments about their bone bank techniques showed that 45% of clinical hospitals use allogeneic bone implants among other implants. In 1989, the year of the official survey, allogeneic bone was transplanted about 6000 times in these clinical hospitals. Despite of this high transplantation frequency important differences turn out regarding selection and testing of recipients, transplantation storage and treatment. A lot of clinical hospitals do not perform important donor examinations inspite of proven transmission risks of bacterial and viral diseases by deep frozen bone. A trend analysis shows that despite of the risk of an HIV-transmission and the resulting difficulties in the logistic of the bone bank, the transplantation frequency allogeneic bone stays constant. The official surveys prove the large range of bone bank techniques and should give rise to make efforts to take note of the recommendations for bone banking techniques.

  9. Canine models of bone marrow transplantation.

    Science.gov (United States)

    Ladiges, W C; Storb, R; Thomas, E D

    1990-01-01

    Progress in experimental bone marrow transplantation in dogs has provided for the direct transfer of research data to the clinical setting and the therapeutic application of marrow grafting to a variety of human diseases. Animal models of total body irradiation, engraftment and graft-versus-host disease are still needed to solve the existing clinical problems of marrow transplantation. Therefore, work in various canine model systems continues to be of interest. Pet dogs with spontaneously occurring lymphomas are used to study the clinical parameters necessary for applying the technique of transplanting their own marrow (autologous), in conjunction with high dose radiation and/or chemotherapy, to human patients with cancer. A major consideration in the successful transplantation of donor bone marrow (allogeneic) is overcoming histocompatibility barriers to assure engraftment and the prevention of graft-versus-host disease, a major limiting aspect of clinical marrow transplantation. Chemicals, radiation, radiotherapeutic techniques, antisera and monoclonal antibodies have been and continue to be developed in laboratory bred dogs. These approaches suppress the immune system either nonspecifically by ablation of immune reactive tissue, or specifically by affecting certain types of immune reactive cells. Parameters such as clinical effectiveness (engraftment or prevention of graft-versus-host disease), immune reconstitution and undesirable side affects in long-term survivors are all used to determine whether new technology can be transferred from preclinical canine studies to human bone marrow transplantation protocols.

  10. Secondary skull reconstruction with autogenous split calvarial bone grafts versus nonautogenous materials.

    Science.gov (United States)

    Lee, Hee Jong; Choi, Jong Woo; Chung, In Wook

    2014-07-01

    Skull reconstructions, which can be required for various reasons, including decompressive craniectomy, trauma, and tumors, are challenging issues in plastic surgery. Moreover, obtaining a low complication ratio in secondary skull reconstructions is more difficult than in primary skull reconstructions. Because standardized protocols have not been established, we here compare cranioplasty performance using fresh autogenous split calvarial bone grafts and allogenic or alloplastic materials in secondary revisional cases. Surgical correction of skull defects was performed in 25 patients in our center between 2005 and 2012. Only secondary cranioplasty cases were reviewed retrospectively. There were 17 men and 8 women, with ages ranging from 8 to 62 years at the time of surgery. The mean follow-up was 55.6 months. The surgical procedure in each case was a routine cranioplasty. In most of the cases, a 1-piece split calvarial bone graft was used while minimizing the separation of the bone flap into multiple pieces. In comparison with the skull reconstructional approach using nonautogenous materials, the functional and esthetic results of skull reconstruction using autogenous calvarial bone grafts were better and more consistent in secondary revisional cases. The group that received autogenous calvarial bone grafts showed a reconstruction success rate of 80% without esthetic and functional complications. In contrast, the group that received nonautogenous materials had a 30% success rate. Secondary cranial defect reconstructions with autogenous calvarial bone grafts showed better functional and esthetic results than skull reconstructions with nonautogenous materials.

  11. Radiobiological studies on target cell populations in murine bone marrow transplantation recipients.

    NARCIS (Netherlands)

    van Os, Ronald Peter

    1994-01-01

    The experiments presented in this thesis were designed to investigate the role of total body irradiation (TBI) in conditioning murine recipients of syngeneic and allogeneic bone marrow transplantation (BMT). ... Zie: Summary

  12. Reducing macrophages to improve bone marrow stromal cell survival in the contused spinal cord.

    NARCIS (Netherlands)

    Ritfeld, G.J.; Nandoe, R.D.S.; Rahiem, S.T.; Hurtado, A.; Roos, R.A.; Grotenhuis, A.; Oudega, M.

    2010-01-01

    We tested whether reducing macrophage infiltration would improve the survival of allogeneic bone marrow stromal cells (BMSC) transplanted in the contused adult rat thoracic spinal cord. Treatment with cyclosporine, minocycline, or methylprednisolone all resulted in a significant decrease in

  13. Allogeneic Bone Marrow Transplant for Inherited Metabolic Disorders

    Science.gov (United States)

    2018-01-09

    Mucopolysaccharidosis; Hurler Syndrome; Hunter Syndrome; Maroteaux-Lamy Syndrome; Sly Syndrome; Alpha Mannosidosis; Fucosidosis; Aspartylglucosaminuria; Adrenoleukodystrophy (ALD); Krabbe Disease; Metachromatic Leukodystrophy (MLD); Sphingolipidoses; Peroxisomal Disorders

  14. Transfusion of shed mediastinal blood reduces the use of allogenic blood transfusion without increasing complications.

    Science.gov (United States)

    Folkersen, Lars; Tang, Mariann; Grunnet, Niels; Jakobsen, Carl-Johan

    2011-03-01

    Reduced use of allogenic blood components is a key issue in cardiac surgery. Several methods to conserve blood have been used; reinfusion of shed mediastinal blood (RSMB) has found widespread acceptance, but the efficacy and safety are still debated. The purpose of this study was to evaluate the effects of RSMB on the use of allogenic blood components and selected complications. Six hundred and twenty-three consecutive cardiac surgery patients in three successive periods, of whom patients in the middle period did not receive RSMB due to manufacturer delivery problems, were evaluated. Patients and procedures were characterized by EuroSCORE. Prospective collected data were: units of transfused allogenic blood, fresh frozen plasma (FFP) and platelets, postoperative blood loss and postoperative complications such as dialysis, re-operation due to bleeding, sternal infection and stroke. Length of stay in ICU was used as a general indicator of perioperative complications. The number of patients receiving allogenic blood in periods with RSMB was significantly lower (36.5% versus 54.9%, ptransfused blood units was lower in patients receiving RSMB (2.07 versus 3.41, p=0.029), while FFP (1.34 versus 2.01, p=0.11) and platelets (0.58 versus 0.95, p=0.05) were not statistically significantly different. Postoperative bleeding was lower (759 versus 967 ml, p=0.032) in the periods with RSMB. Patients receiving RSMB were less transfused with allogenic blood and had less postoperative drainage, while the frequency of observed postoperative complications was not different from patients who did not receive RSMB.

  15. Encapsulation of allogeneic mesenchymal stem cells in alginate extends local presence and therapeutic function.

    Science.gov (United States)

    Leijs, M J; Villafuertes, E; Haeck, J C; Koevoet, W J; Fernandez-Gutierrez, B; Hoogduijn, M J; Verhaar, J A; Bernsen, M R; van Buul, G M; van Osch, G J

    2017-01-30

    Bone marrow derived mesenchymal stem cells (MSCs) have immunomodulatory and trophic capacities. For therapeutic application in local chronic inflammatory diseases, MSCs, preferably of allogeneic origin, have to retain immunomodulatory properties. This might be achieved by encapsulation of MSCs in a biomaterial that protects them from the host immune system. Most studies investigating the properties of MSCs for therapeutic application use short term cultures of cells in monolayer. Since the physical environment of MSCs can influence their functionality, we evaluated the feasibility of preserving the immunomodulatory properties of MSCs encapsulated in a three-dimensional alginate construct. After 5 weeks of implantation in immunocompetent rats, active allogeneic MSCs encapsulated in alginate were still detectable by Bio Luminescence Imaging and Magnetic Resonance Imaging of luciferase transduced and superparamagnetic iron oxide labelled MSCs. MSCs injected in saline were only detectable up to 1 week after injection. Moreover, the MSCs encapsulated in alginate responded to inflammatory stimuli similarly to MSCs in monolayer culture. In addition, MSC-alginate beads secreted immunomodulatory and trophic factors and inhibited T-cell proliferation after 30 d of in vitro culture. Our data indicate that allogeneic MSCs encapsulated in alginate persist locally and could act as an interactive immunomodulatory or trophic factor release system for several weeks, making this an interesting system to investigate for application in inflammatory disease conditions.

  16. Desmopressin for minimising perioperative allogeneic blood transfusion.

    Science.gov (United States)

    Henry, D A; Moxey, A J; Carless, P A; O'Connell, D; McClelland, B; Henderson, K M; Sly, K; Laupacis, A; Fergusson, D

    2001-01-01

    Public concerns regarding the safety of transfused blood have prompted re-consideration of the use of allogeneic (from an unrelated donor) red blood cell (RBC) transfusion, and a range of techniques designed to minimise transfusion requirements. To examine the evidence for the efficacy of desmopressin (1-deamino-8-D-arginine-vasopressin), in reducing perioperative blood loss and the need for red cell transfusion in patients who do not have congenital bleeding disorders. Articles were identified by: computer searches of OVID MEDLINE, EMBASE, and Current Contents (to August 2000) and web sites of international health technology assessment agencies (to May 1998). References in the identified trials and review articles were checked and authors contacted to identify additional studies. Randomised controlled parallel group trials in which adult patients, scheduled for non-urgent surgery, were randomised to DDAVP, or to a control group, who did not receive the intervention. Trial quality was assessed using criteria proposed by Schulz et al. (1995) and Jadad et al. (1996). The principal outcomes were: the number of patients exposed to red cells, and the amount of blood transfused. Other clinical outcomes are detailed in the review. Fourteen trials of DDAVP (N=1034) reported data on the proportion of patients exposed to allogeneic RBC transfusion. In subjects treated with DDAVP the relative risk of exposure to peri-operative allogeneic blood transfusion was 0.98 (95%CI: 0.88 to 1.10) compared with control. In DDAVP-treated patients the relative risk of requiring re-operation due to bleeding was 0.56 (95%CI: 0.18 to 1.73). There was no statistically significant effect overall for mortality and non-fatal myocardial infarction in DDAVP-treated patients compared with control (RR=1.53: 95%CI: 0.58 to 4.05) and (RR=1.52: 95%CI: 0.67 to 3.49) respectively. There is no convincing evidence that desmopressin minimises perioperative allogeneic RBC transfusion in patients who do not

  17. Induction therapy with vincristine, adriamycin, dexamethasone (VAD) and intermediate-dose melphalan (IDM) followed by autologous or allogeneic stem cell transplantation in newly diagnosed multiple myeloma.

    Science.gov (United States)

    Lokhorst, H M; Sonneveld, P; Cornelissen, J J; Joosten, P; van Marwijk Kooy, M; Meinema, J; Nieuwenhuis, H K; van Oers, M H; Richel, D J; Segeren, C N; Veth, G; Verdonck, L F; Wijermans, P W

    1999-02-01

    We performed a phase II study to test the efficacy and feasibility of induction therapy with vincristine, adriamycin and dexamethasone (VAD) and intermediate-dose melphalan, 70 mg/m2 (IDM), to autologous or allogeneic stem cell transplantation in newly diagnosed multiple myeloma (MM). A total of 77 patients received two cycles of VAD (n = 62) and/or two cycles of i.v. IDM 70 mg/m2 (n = 15) combined with G-CSF. PBSC were harvested after the first IDM, successfully in 87% of patients. Patients with a response to induction received myeloablative therapy with PBSCT (n = 50) followed by IFN maintenance or allo-BMT (n = 11). Seventy-two per cent of patients achieved a response after VAD which increased to 85% after IDM. Of patients who received PBSCT and allo-BMT, 24% and 45% achieved CR, respectively. Toxicity of induction consisted mainly of bone marrow suppression after IDM (median 8 days) with prolonged aplasia in 11% of patients after the second IDM. Only six infections WHO grade 3 occurred during induction. Treatment-related mortality of PBSCT and allo-BMT was 6% and 18%, respectively. Median time of follow-up is 44 months, and 50% of patients after PBSCT and 60% of patients after allo-BMT are still in remission. Survival rates of all patients were 82%, 75% and 63%, and for transplanted patients 86%, 79% and 68% after 12, 24 and 36 months. Well known prognostic factors, including alpha-IFN maintenance after PBSCT, were not significant for response or survival although patients in CR after allo-BMT had a strong tendency for better outcome. VAD/IDM is an effective and safe induction therapy for autologous and allogeneic stem cell transplantation. Based on these observations a phase III trial was started in October 1995 comparing IFN maintenance with PBSCT and allo-BMT after response to induction with VAD and IDM.

  18. Pubovaginal bone anchor fixation with polyethylene versus fascia lata slings in the treatment of female stress incontinence: sling material and processing are predominant factors in success.

    Science.gov (United States)

    Schulte-Baukloh, H; Thalau, F; Stürzebecher, B; Knispel, H H

    2005-04-01

    The opponents of the In-Taca bone anchor system note the risk of a high rate of wound infection and osteitis pubis. We evaluated whether there is a difference in the outcome of the use of two different sling materials--polyethylene and fascia lata--with regard to wound infection, and analyzed the incidence of osteitis pubis further in a larger series. A total of 61 women (mean age = 65.4 years) were treated for stress urinary incontinence (SUI) type II and III using the In-Taca bone anchor system. In 15 of 61 patients, we used a synthetic sling of polyethylene, and in 46, a fascia lata sling. The subjective success rate was determined with validated questionnaires (Urinary Distress Inventory-6, Symptom Severity Index and Symptom Impact Index). The objective assessment included a pad test according to the ICS- standard and a urogynecologic evaluation. Mean follow-up was 10.2 months. Wound inflammation of only very mild degree occurred in 15% in the fascia lata group, whereas 33% in the polyethylene group developed serious sling infection; in three patients explantation of the sling was necessary. Accordingly, satisfaction with the procedure was low in the polyethylene group. In both groups, there were no hints of osteitis pubis. The sling material used did not affect continence rate. Using the bone anchor system, the infection rate depends primarily on the sling material used and its processing: polyethylene is well tolerated in other reconstructive procedures (such as TVT, where a netlike mesh is used), so the processing of synthetic sling material plays an extremely important role in infection rate: platelike, dense synthetic material tends to cause wound infection.

  19. Silicate-doped hydroxyapatite and its promotive effect on bone mineralization

    Science.gov (United States)

    Qiu, Zhi-Ye; Noh, In-Sup; Zhang, Sheng-Min

    2013-03-01

    Bone defect is one of the most common diseases in clinic. Existing therapeutic approaches have encountered many problems, such as lack of autogenous allogeneic bone and immunological rejection to allogeneic implant. Synthetic hydroxyapatite (HA) provided solutions for bone repair, since the HA is the main inorganic component of animals' bone. However, HA has good biocompatibility, but does not possess osteogenic capability, which is of significance for modern bone repair materials. Si is an essential trace element in bone tissue, and it has been demonstrated to be able to promote bone formation. Therefore, silicate-doped hydroxyapatite (Si-HA) may serve as a promising material for bone repair, and promote bone regeneration in the repair. The current review discusses development of Si-HA, focusing on its preparation and characterization, in vitro and in vivo evaluations of the material, positive effect of Si-HA on promoting bone formation in clinical applications, and molecular mechanism investigation of such promotive effect.

  20. Allogeneic fibroblasts in dermal substitutes induce inflammation and scar formation

    NARCIS (Netherlands)

    Lamme, Evert N.; van Leeuwen, Rene T. J.; Mekkes, Jan R.; Middelkoop, Esther

    2002-01-01

    In the present study, we compared the use of autologous versus allogeneic fibroblasts in dermal skin substitutes in a porcine wound model. The allogeneic fibroblast populations were isolated from female and a male pig (allo-1, - 2 and - 3) and the controls, autologous fibroblasts, from female

  1. Bone morphogenetic protein-15 in follicle fluid combined with age may differentiate between successful and unsuccessful poor ovarian responders

    Directory of Open Access Journals (Sweden)

    Wu Yan-Ting

    2012-12-01

    Full Text Available Abstract Background The counselling of poor ovarian responders about the probability of pregnancy remains a puzzle for gynaecologists. The aim of this study was to optimise the management of poor responders by investigating the role of the oocyte-derived factor bone morphogenetic protein-15 (BMP-15 combined with chronological age in the prediction of the outcome of in-vitro fertilisation-embryo transfer (IVF-ET in poor responders. Methods A retrospective study conducted in a university hospital. A total of 207 poor ovarian responders who reached the ovum pick-up stage undergoing IVF/intracytoplasmic sperm injection (ICSI with three or fewer follicles no less than 14 mm on the day of oocyte retrieval were recruited from July 1, 2008 to December 31, 2009. Another 215 coinstantaneous cycles with normal responses were selected as controls. The BMP-15 levels in the follicular fluid (FF of the 207 poor responders were analysed by western blot. Based on the FF BMP-15 level and age, poor responders were sub-divided into four groups. The main outcome measures were the FF BMP-15 level, implantation rate, pregnancy rate, and live birth rate. Results The implantation rate (24.2% vs. 15.3%, chemical pregnancy rate (40% vs. 23.7%, clinical pregnancy rate (36.5% vs. 20.4% and live birth rate (29.4% vs. 15.1% in the high BMP-15 group were significantly higher than those in the low BMP-15 group. Furthermore, poor responders aged less than or equal to 35 years with a higher FF BMP-15 level had the best implantation, pregnancy and live birth rates, which were comparable with those of normal responders. Conclusions Our study suggests a potential role of BMP-15 in the prediction of the IVF outcome. A high FF BMP-15 combined with an age less than or equal to 35 years may be used as a potential indicator for repeating IVF cycles in poor ovarian responders.

  2. Rhinosinusitis in autologous and allogeneic bone marrow transplantation: a retrospective study on the performance of imaging studies on severity and prognostic evaluation Rinossinusite em transplante de células-tronco hematopoéticas autólogo e alogênico: um estudo retrospectivo sobre o desempenho de estudos de imagem na avaliação de severidade e prognóstico

    Directory of Open Access Journals (Sweden)

    Leo Sekine

    2010-02-01

    Full Text Available The objective of this work was to evaluate the diagnostic and prognostic performance of a traditional imaging staging system for rhinosinusitis in the bone marrow transplantation (BMT scenario. A retrospective cohort study was carried out at a bone marrow transplantation referral center involving subjects who underwent allogeneic or autologous BMT from September 1st 2005 to September 31st 2007 and later evolved with rhinosinusitis during the BMT inpatient period. Patients who had a previous history of sinusal disease or otolaryngologic surgery were excluded from the study. Data concerning mortality, the treatment of rhinosinusitis and BMT outcomes were extracted from medical files. The collected parameters were compared to the Lund-Mackay tomographic staging system score which was calculated based on available tomography films of each patient. A total of 85 BMT were performed and 23 allogeneic and 14 autologous (43.5% BMT patients evolved with rhinosinusitis during transplantation. A significant association with LMS was found for the absolute neutrophil count (ANC, with a higher ANC (>500/mm3 correlating with a higher LMS (Mean LMS for lower ANC 6.08 and higher ANC 9.71 points, pO objetivo deste trabalho foi avaliar o desempenho diagnóstico e prognóstico de um escore de estadiamento de rinossinusite (RS por tomografia em pacientes submetidos a transplante de medula óssea (TMO. Realizou-se um estudo de coorte retrospectivo de pacientes submetidos a transplante de medula óssea (autólogo e alogênico de 1º de setembro de 2005 a 31 de setembro de 2007 que desenvolveram RS durante o período de internação do transplante. Pacientes com história prévia de doença sinusal ou cirurgia otorrinolaringológica foram excluídos do estudo. Dados relacionados à mortalidade, resolução da RS e desfechos do TMO foram extraídos do prontuário médico. Os parâmetros coletados foram correlacionados com o escore de estadiamento de Lund-Mackay (ELM, que

  3. CD4+CD25+FOXP3+ Regulatory T Cells In Allogeneic Hematopoietic Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Young-Ho Lee

    2011-06-01

    Full Text Available CD4+CD25+FOXP3+ regulatory T cells (Treg require activation through the T cell receptor for function. CD4+CD25+FOXP3+ regulatory T cells are believed to be key players of the immune tolerance network and control the induction and effector phase of the immune system. Although these cells require antigen-specific activation, they are generally able to suppress bystander T cell responses once activated. This raises the possibility that antigen-specific Treg may be useful therapeutically by localizing generalized suppressive activity to tissues expressing select target antigens. Treg can exert a potent suppressive effect on immune effector cells reactive to host antigens and prevent graft versus host disease (GVHD in allogeneic bone marrow transplantation (BMT. Here, we observed that co-transfer of CD4+CD25+FOXP3+ T cells derived from donor type along with the donor bone marrow cells could control GVHD-like reactions by suppressing effectors cells of host responding to the donor hematopoietic compartment, and resulted in prevention of autoimmunity and rejection. We further demonstrate that CD4+CD25+FOXP3+ regulatory T cells can control immune-based morbidity after allogeneic BMT by suppressing the development of granulocytes cells and increasing the level of B cell expression.

  4. The role of bone void fillers in medial opening wedge high tibial osteotomy: a systematic review.

    Science.gov (United States)

    Slevin, Omer; Ayeni, Olufemi R; Hinterwimmer, Stefan; Tischer, Thomas; Feucht, Matthias J; Hirschmann, Michael T

    2016-11-01

    A variety of bone void filling materials and methods are available in opening medial wedge HTO (OWHTO). The pertinent question revolves around if and when bone void fillers are needed. The primary purpose of this study was to systematically review outcomes and complications after OWHTO with and without the use of bone void fillers. The EMBASE, PubMed\\MEDLINE, Cochrane Library and Google Scholar databases were searched to identify articles that reported OWHTO results using different bone void fillers until March 2016. Only articles reporting the exact bone void filler type, the opening gap size and the fixation method were included. The extracted data included the study design, demographic data, the radiological and clinical results and complication rates. Outcomes were analysed with regard to bone void filler type, and comparison was made between the groups (allograft, autograft, synthetic bone void filler and OWHTO without bone void filling). Twenty-two articles reporting the results of 1421 OWHTO met the inclusion criteria. In total, 647 osteotomies were completed with allogeneic graft as bone void filler, 367 with synthetic materials, 199 with autograft and 208 without any bone void filling material. The maximum opening gap size was similar in all groups with mean of 9.8 mm (range 4-17.5 mm). Locking plate fixation was used in 90 % of the osteotomies that were completed without bone void filler, while all allograft cases and more then 90 % of the autograft cases were done with non-locking systems. The highest rates of non-union (1.1 %) were seen in the synthetic group, compared to 0.5 % in the all the other groups. This systematic review showed no definitive advantages for OWHTO with any bone void filler in terms of union rates and loss of correction. Moreover, the use of autografts or allografts showed more favourable outcomes than synthetic bone substitutes. OWHTO with gaps smaller then 10 mm and rigid fixation might be successfully managed without

  5. [Experimental study of allogenic tendon with sheath grafting in chicken].

    Science.gov (United States)

    Zhang, Y L; Wang, S L; Gao, X S

    2001-03-01

    To investigate availability of deep freeze stored allogenic tendon with sheath grafting in repairing the tendon and sheath defect in the II area of flexor digitorum tendon. Sixty chickens with tendon and sheath defect were divided into 2 groups randomly, group A was treated with allogenic grafting and group B was treated with autogenic grafting, these two groups were divided into two subgroups respectively, they were, group A1 allogenic tendon with whole sheath grafting, group A2 allogenic tendon with partial sheath grafting, group B1 autogenic tendon with whole sheath grafting and group B2 autogenic tendon with whole sheath grafting. All the allogenic grafts were treated by deep freeze. Histomorphological study, histoimmunological study and slipping function of the grafts were measured after operation. In group A1 and B1, the local reaction was sever, the nutrition of tendon graft was barricaded by the whole sheath resulting in adhesion, degeneration and necrosis. In group A2 and B2, the tendon graft healed well and little adhesion existed between tendon and sheath. The results showed that there were significant differences between tendon grafting with whole sheath and tendon grafting with partial sheath. Deep freeze store can reduce the immunogenicity of allogenic tendon with sheath. Allogenic tendon with partial sheath grafting can be used as a new biological material for repairing the tendon and sheath defect.

  6. Mast Cell Leukemia: Review of a Rare Disease and Case Report of Prolonged Survival after Allogeneic Stem Cell Transplant

    Directory of Open Access Journals (Sweden)

    James Bauer, MD, PhD

    2017-11-01

    Full Text Available Mast cell leukemia is a rare and aggressive form of mastocytosis characterized by >20% mast cells found in the bone marrow aspirates of patients with signs of systemic mastocytosis-related organ damage. The prognosis for patients with mast cell leukemia is extremely poor, with resistance to both cytoreductive therapies and tyrosine kinase inhibitors being relatively common. While allogeneic hematopoietic stem cell transplantation has been associated with long-term survival in patients with advanced systemic mastocytosis, reports regarding its effectiveness in mast cell leukemia are limited to fewer than 20 cases described in the literature. Here, we report a patient with mast cell leukemia who remains in complete remission 24 months after allogeneic HSCT at the time of this writing, and briefly review the clinical, diagnostic, and therapeutic approaches to this rare disease.

  7. Use and preservation methods of bone grafts in small animals

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    Rafael Garabet Agopian

    2016-09-01

    Full Text Available The present review describes the main characteristics of bone grafts used in small animals. Bone grafts are tissues without vasculature, which facilitate the production of new bone cells with osteogenic and osteoinductive factors that lead to the differentiation of cells and structural support for bone marrow. The transplant of a graft is followed by three stages: osteogenesis, or the formation of new bone; osteoinduction, which is the differentiation of cells; and osteoconduction, the process of growth of mesenchymal cells and capillaries that results in new bone formation. The composition of bone grafts may include spongy bone, cortical bone, cortical-spongy bone, cartilage or bone marrow. Grafts can also be classified according to their origin, being autogenous tissue when they are transplanted from the same individual, allogenous (homologous when originating from another individual of the same species, and xenogenous when obtained from a different species.

  8. Storage and allogeneic transplantation of peripheral nerve using a green tea polyphenol solution in a canine model

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    Noguchi Takashi

    2010-11-01

    Full Text Available Abstract Background In our previous study, allogeneic-transplanted peripheral nerve segments preserved for one month in a polyphenol solution at 4°C could regenerate nerves in rodents demonstrated the same extent of nerve regeneration as isogeneic fresh nerve grafts. The present study investigated whether the same results could be obtained in a canine model. Methods A sciatic nerve was harvested from a male beagle dog, divided into fascicules of Sry and β-actin to investigate whether cells of donor origin remained in the allogeneic nerve segments. FK506 concentration was measured in blood samples taken before the animals were killed. Results The total myelinated axon numbers and amplitudes of the muscle action potentials correlated significantly with the blood FK506 concentration. Few axons were observed in the allogeneic-transplanted nerve segments in the PA0.025 group. PCR showed clear Sry-specific bands in specimens from the PA0.1 and PA0.05 groups but not from the PA0.025 group. Conclusions Successful nerve regeneration was observed in the polyphenol-treated nerve allografts when transplanted in association with a therapeutic dose of FK506. The data indicate that polyphenols can protect nerve tissue from ischemic damage for one month; however, the effects of immune suppression seem insufficient to permit allogeneic transplantation of peripheral nerves in a canine model.

  9. Cellular adoptive immunotherapy after allogeneic stem cell transplantation.

    NARCIS (Netherlands)

    Schattenberg, A.V.M.B.; Dolstra, H.

    2005-01-01

    PURPOSE OF REVIEW: This review presents the role of donor lymphocyte infusion, natural killer cells, and dendritic cells in cellular immunotherapy after allogeneic stem cell transplantation. RECENT FINDINGS: It becomes increasingly possible to infuse more specialized subsets of lymphocyte cells

  10. Management of the exposure of a dense PTFE (d-PTFE) membrane in guided bone regeneration (GBR): a case report.

    Science.gov (United States)

    Ghensi, P; Stablum, W; Bettio, E; Soldini, M C; Tripi, T R; Soldini, C

    2017-01-01

    Guided bone regeneration (GBR) is a well-established and generally predictable method for repairing alveolar ridge defects and preparing edentulous sites for implant placement. Standard GBR involves filling the space underneath a membrane with autogenous bone or a mixture composed of autogenous bone particles and allogeneic bone tissue or heterologous biomaterials. The use of a barrier membrane for GBR has sometimes been associated with complications, however - reportedly involving exposure, infection, and collapse - and the non-resorbable types of membrane seem to be involved more often than the resorbable solutions. Such complications may be severe enough to defeat the object of the GBR procedure. A non-resorbable high-density polytetrafluoroethylene (d-PTFE) membrane has recently been designed specifically for use in bone-augmentation procedures that seems to assure a good bone regeneration process even when the membrane is exposed to the oral cavity. This case report describes an exposure of a d-PTFE membrane occurring after a maxillary GBR procedure and how it was overcome successfully, enabling implants insertion.

  11. Bone tumor

    Science.gov (United States)

    Tumor - bone; Bone cancer; Primary bone tumor; Secondary bone tumor; Bone tumor - benign ... The cause of bone tumors is unknown. They often occur in areas of the bone that grow rapidly. Possible causes include: Genetic defects passed down ...

  12. Present and future of allogeneic natural killer cell therapy

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    Okjae eLim

    2015-06-01

    Full Text Available Natural killer (NK cells are innate lymphocytes that are capable of eliminating tumor cells and are therefore used for cancer therapy. Although many early investigators used autologous NK cells, including lymphokine-activated killer cells, the clinical efficacies were not satisfactory. Meanwhile, human leukocyte antigen (HLA-haploidentical hematopoietic stem cell transplantation revealed the anti-tumor effect of allogeneic NK cells, and HLA-haploidentical, killer cell immunoglobulin-like receptor (KIR ligand-mismatched allogeneic NK cells are currently used for many protocols requiring NK cells. Moreover, allogeneic NK cells from non-HLA-related healthy donors have been recently used in cancer therapy. The use of allogeneic NK cells from non-HLA-related healthy donors allows the selection of donor NK cells with higher flexibility and to prepare expanded, cryopreserved NK cells for instant administration without delay for ex vivo expansion. In cancer therapy with allogeneic NK cells, optimal matching of donors and recipients is important to maximize the efficacy of the therapy. In this review, we summarize the present state of allogeneic NK cell therapy and its future directions.

  13. Sixteen adult patients with acute leukemia treated by chemotherapy, total body irradiation and allogeneic marrow transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Kodera, Yoshihisa; Morishima, Yasuo; Morishita, Yoshihisa (Nagoya Univ. (Japan). Faculty of Medicine)

    1984-12-01

    Since 1976, 16 adult patients with acute leukemia have been treated by chemotherapy, total body irradiation (TBI) and allogeneic bone marrow transplantation (BMT) in the medical school hospital and the satellite hospitals of Nagoya University. The first group of 10 patients were given marrow grafts at the time of leukemic relapse and the second group of six patients were given the grafts in the period of remission of their disease. For the first group (ALL/ANLL 2:8, age (median) 33, M/F 8:2), HLA-identical donor cells (25 x 10/sup 7//kg(median)) were infused after the patients were conditioned with NSC D 245382 (ACNU) or daunorubicin, cyclophosphamide (CY) and a single shot of 1000 rad of TBI. For the second group (ALL/ANLL 4:2, age (median) 20, M/F 5:1), HLA-identical donor cells (22 x 10/sup 7//kg(median)) were infused after the patients were conditioned with CY and fractionated (250 rad x 4) TBI. All the patients were isolated in a laminar air flow room (LAF) after gut and skin decontamination. Engraftment of donor cells was confirmed in 15 out of the 16 patients. Febrile periods in LAF and the days required for platelet transfusion were prolonged in the first group. All the patients in the first group died within 12-214 days after BMT because of interstitial pneumonitis (7 patients) or bacterial infection (3 patients). On the other hand, five out of six patients in the second group are alive 84-540 days after BMT. For the surviving patients, the complications of chronic graft versus host disease, viral infections, tuberculosis, hepatitis, hemorrhagic cystitis and recurrence of leukemia are now the problems. It can be stated that the patient's clinical condition at the time of BMT is one of the most essential factors for the success of BMT although the effects of other variables, such as a change in the conditioning regimens or the supportive care, must also be carefully analyzed.

  14. Multiple intravenous injections of allogeneic equine mesenchymal stem cells do not induce a systemic inflammatory response but do alter lymphocyte subsets in healthy horses.

    Science.gov (United States)

    Kol, Amir; Wood, Joshua A; Carrade Holt, Danielle D; Gillette, Jessica A; Bohannon-Worsley, Laurie K; Puchalski, Sarah M; Walker, Naomi J; Clark, Kaitlin C; Watson, Johanna L; Borjesson, Dori L

    2015-04-15

    Intravenous (IV) injection of mesenchymal stem cells (MSCs) is used to treat systemic human diseases and disorders but is not routinely used in equine therapy. In horses, MSCs are isolated primarily from adipose tissue (AT) or bone marrow (BM) and used for treatment of orthopedic injuries through one or more local injections. The objective of this study was to determine the safety and lymphocyte response to multiple allogeneic IV injections of either AT-derived MSCs (AT-MSCs) or BM-derived MSCs (BM-MSCs) to healthy horses. We injected three doses of 25 × 10(6) allogeneic MSCs from either AT or BM (a total of 75 × 10(6) MSCs per horse) into five and five, respectively, healthy horses. Horses were followed up for 35 days after the first MSC infusion. We evaluated host inflammatory and immune response, including total leukocyte numbers, serum cytokine concentration, and splenic lymphocyte subsets. Repeated injection of allogeneic AT-MSCs or BM-MSCs did not elicit any clinical adverse effects. Repeated BM-MSC injection resulted in increased blood CD8(+) T-cell numbers. Multiple BM-MSC injections also increased splenic regulatory T cell numbers compared with AT-MSC-injected horses but not controls. These data demonstrate that multiple IV injections of allogeneic MSCs are well tolerated by healthy horses. No clinical signs or clinico-pathologic measurements of organ toxicity or systemic inflammatory response were recorded. Increased numbers of circulating CD8(+) T cells after multiple IV injections of allogeneic BM-MSCs may indicate a mild allo-antigen-directed cytotoxic response. Safety and efficacy of allogeneic MSC IV infusions in sick horses remain to be determined.

  15. Allogeneic transplantation of fetal membrane-derived mesenchymal stem cell sheets increases neovascularization and improves cardiac function after myocardial infarction in rats.

    Science.gov (United States)

    Ishikane, Shin; Hosoda, Hiroshi; Yamahara, Kenichi; Akitake, Yoshiharu; Kyoungsook, Jung; Mishima, Kenichi; Iwasaki, Katsunori; Fujiwara, Michihiro; Miyazato, Mikiya; Kangawa, Kenji; Ikeda, Tomoaki

    2013-10-27

    Mesenchymal stem cell (MSC) transplantation has been pursued as a new method to repair damaged myocardium. We focused on the fetal membrane (FM) as an alternative source to bone marrow (BM)-derived MSCs. In this study, we investigated whether transplantation of allogeneic FM-MSC sheets could attenuate myocardial dysfunction in a rat chronic myocardial infarction (MI) model. Sheets of allogeneic FM-MSC or autologous BM-MSC were transplanted into the scarred myocardium 4 weeks after coronary ligation. Four weeks after transplantation, both allogeneic FM-MSC and autologous BM-MSC sheets had significantly improved cardiac function and reduced myocardial fibrosis compared with the untreated MI group. In both MSC sheet-transplanted groups, the peri-infarct regional capillary density was increased. Some engrafted MSCs formed vascular structures and were positive for lectin I and α-smooth muscle actin. The numbers of engrafted cells and differentiated cells were very low after both types of MSC sheet transplantation. CD3 T cells did not increase in the transplantation site, but CD163 M2 macrophages increased in the groups transplanted with allogeneic FM-MSC and autologous BM-MSC. Transplantation of allogeneic FM-MSC or autologous BM-MSC sheets attenuated myocardial dysfunction in a rat MI model to a similar degree. The engraftment rate of transplanted cells and immune cell infiltration into the transplanted area did not differ between the two types of MSC transplants. M2 macrophage induction has possible involvement in the therapeutic effects of MSC transplantation. Allogeneic FM-MSC sheet transplantation might be a new therapeutic strategy after MI.

  16. NEW BIOKERATOPROSTHETIC COMPLEX BASED ON MODIFIED ALLOGENIC DONOR CORNEAS AND CULTURED POSTNATAL HUMAN SKIN FIBROBLASTS

    Directory of Open Access Journals (Sweden)

    S. A. Borzenok

    2011-01-01

    Full Text Available The aim of the study was to develop biokeratoprosthetic complex based on cross-linking modified allogenic donor corneas and cultured postnatal human skin fibroblasts. Cross-linking enhances corneal strength and tole- rance to proteolytic enzymes. Fibroblasts’ proliferation and migration in the intrastromal pocket stimulates fiber syncytium formation and collagen microcarriers integration into the corneal stroma, as well as intercellular ma- trix formation around the prosthetic metallic plate as early as the cocultivation stage. A new biokeratoprosthetic complex has been successfully developed for further in vivo studies. 

  17. Suspected Pulmonary Infection with Trichoderma longibrachiatum after Allogeneic Stem Cell Transplantation.

    Science.gov (United States)

    Akagi, Tomoaki; Kawamura, Chizuko; Terasawa, Norio; Yamaguchi, Kohei; Kubo, Kohmei

    2017-01-01

    Aspergillus and Candida species are the main causative agents of invasive fungal infections in immunocompromised human hosts. However, saprophytic fungi are now increasingly being recognized as serious pathogens. Trichoderma longibrachiatum has recently been described as an emerging pathogen in immunocompromised patients. We herein report a case of isolated suspected invasive pulmonary infection with T. longibrachiatum in a 29-year-old man with severe aplastic anemia who underwent allogeneic stem cell transplantation. A direct microscopic examination of sputum, bronchoaspiration, and bronchoalveolar lavage fluid samples revealed the presence of fungal septate hyphae. The infection was successfully treated with 1 mg/kg/day liposomal amphotericin B.

  18. Intraarticular Injection of Allogenic Mesenchymal Stem Cells has a Protective Role for the Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Xin Yang

    2015-01-01

    Full Text Available Background: Researchers initially proposed the substitution of apoptotic chondrocytes in the superficial cartilage by injecting mesenchymal stem cells (MSCs intraarticularly. This effect was termed as bio-resurfacing. Little evidence supporting the treatment of osteoarthritis (OA by the delivery of a MSC suspension exists. The aim of this study was to investigate the effects of injecting allogenic MSCs intraarticularly in a rat OA model and to evaluate the influence of immobility on the effects of this treatment. Methods: We established a rat knee OA model after 4 and 6 weeks and cultured primary bone marrow MSCs. A MSC suspension was injected into the articular space once per week for 3 weeks. A subgroup of knee joints was immobilized for 3 days after each injection, while the remaining joints were nonimmobilized. We used toluidine blue staining, Mankin scores, and TdT-mediated dUTP-biotin nick end labeling staining to evaluate the therapeutic effect of the injections. Comparisons between the therapy side and the control side of the knee joint were made using paired t-test, and comparisons between the immobilized and nonimmobilized subgroups were made using the unpaired t-test. A P value 0.05. Conclusions: Therapy involving the intraarticular injection of allogenic MSCs promoted cartilage repair in a rat arthritis model, and 3-day immobility after injection had little effect on this therapy.

  19. Hematopoietic stem cells from NOD mice exhibit autonomous behavior and a competitive advantage in allogeneic recipients.

    Science.gov (United States)

    Chilton, Paula M; Rezzoug, Francine; Ratajczak, Mariusz Z; Fugier-Vivier, Isabelle; Ratajczak, Janina; Kucia, Magda; Huang, Yiming; Tanner, Michael K; Ildstad, Suzanne T

    2005-03-01

    Type 1 diabetes is a systemic autoimmune disease that can be cured by transplantation of hematopoietic stem cells (HSCs) from disease-resistant donors. Nonobese diabetic (NOD) mice have a number of features that distinguish them as bone marrow transplant recipients that must be understood prior to the clinical application of chimerism to induce tolerance. In the present studies, we characterized NOD HSCs, comparing their engraftment characteristics to HSCs from disease-resistant strains. Strikingly, NOD HSCs are significantly enhanced in engraftment potential compared with HSCs from disease-resistant donors. Unlike HSCs from disease-resistant strains, they do not require graft-facilitating cells to engraft in allogeneic recipients. Additionally, they exhibit a competitive advantage when coadministered with increasing numbers of syngeneic HSCs, produce significantly more spleen colony-forming units (CFU-Ss) in vivo in allogeneic recipients, and more granulocyte macrophage-colony-forming units (CFU-GMs) in vitro compared with HSCs from disease-resistant controls. NOD HSCs also exhibit significantly enhanced chemotaxis to a stromal cell-derived factor 1 (SDF-1) gradient and adhere significantly better on primary stroma. This enhanced engraftment potential maps to the insulin-dependent diabetes locus 9 (Idd9) locus, and as such the tumor necrosis factor (TNF) receptor family as well as ski/sno genes may be involved in the mechanism underlying the autonomy of NOD HSCs. These findings may have important implications to understand the evolution of autoimmune disease and impact on potential strategies for cure.

  20. Inflammatory effects of autologous, genetically modified autologous, allogeneic, and xenogeneic mesenchymal stem cells after intra-articular injection in horses.

    Science.gov (United States)

    Pigott, J H; Ishihara, A; Wellman, M L; Russell, D S; Bertone, A L

    2013-01-01

    To compare the clinical and inflammatory joint responses to intra-articular injection of bone marrow-derived mesenchymal stem cells (MSC) including autologous, genetically modified autologous, allogeneic, or xenogeneic cells in horses. Six five-year-old Thoroughbred mares had one fetlock joint injected with Gey's balanced salt solution as the vehicle control. Each fetlock joint of each horse was subsequently injected with 15 million MSC from the described MSC groups, and were assessed for 28 days for clinical and inflammatory parameters representing synovitis, joint swelling, and pain. There were not any significant differences between autologous and genetically modified autologous MSC for synovial fluid total nucleated cell count, total protein, interleukin (IL)-6, IL-10, fetlock circumference, oedema score, pain-free range-of-motion, and soluble gene products that were detected for at least two days. Allogeneic and xenogeneic MSC produced a greater increase in peak of inflammation at 24 hours than either autologous MSC group. Genetically engineered MSC can act as vehicles to deliver gene products to the joint; further investigation into the therapeutic potential of this cell therapy is warranted. Intra-articular MSC injection resulted in a moderate acute inflammatory joint response that was greater for allogeneic and xenogeneic MSC than autologous MSC. Clinical management of this response may minimize this effect.

  1. Healing of cortical bone grafts in athymic rats

    Energy Technology Data Exchange (ETDEWEB)

    Kirkeby, O.J.; Nordsletten, L.; Skjeldal, S. (Institute for Surgical Research, University of Oslo, Oslo (Norway))

    1992-01-01

    We studied healing of allogeneic and syngeneic cortical tibial segment grafts in athymic and normal rats. After 3, 6, and 12 weeks, the weight, circulation; and mineralization rate of the healing segment, and mechanical strength and stiffness of the healing tibia were measured. There were no differences between allogeneic and syngeneic grafts in athymic and normal animals at 3 or 6 weeks. After 12 weeks, the vascularization and mineralization of the grafts, but not of the surrounding callus, were smaller in the allogeneic grafts in the normal recipients than in the other groups. Also after 12 weeks, the stiffness of the healing tibiae was less in allogeneic grafts in normal recipients than in the other groups. The strength of the allogeneic grafts was less than the strength of the syngeneic grafts in both athymic and normal recipients. This suggests that T-cell-mediated rejection is responsible for decreased vascularization and mineralization of alogenecic bone and that the difference in strength between allogeneic and syngeneci grafts in not due to T-lymphocyte graft rejection. (au).

  2. Biodistribution and Immunogenicity of Allogeneic Mesenchymal Stem Cells in a Rat Model of Intraarticular Chondrocyte Xenotransplantation

    Directory of Open Access Journals (Sweden)

    Maribel Marquina

    2017-11-01

    Full Text Available Xenogeneic chondrocytes and allogeneic mesenchymal stem cells (MSC are considered a potential source of cells for articular cartilage repair. We here assessed the immune response triggered by xenogeneic chondrocytes when injected intraarticularly, as well as the immunoregulatory effect of allogeneic bone marrow-derived MSC after systemic administration. To this end, a discordant xenotransplantation model was established by injecting three million porcine articular chondrocytes (PAC into the femorotibial joint of Lewis rats and monitoring the immune response. First, the fate of MSC injected using various routes was monitored in an in vivo imaging system. The biodistribution revealed a dependency on the injection route with MSC injected intravenously (i.v. succumbing early after 24 h and MSC injected intraperitoneally (i.p. lasting locally for at least 5 days. Importantly, no migration of MSC to the joint was detected in rats previously injected with PAC. MSC were then administered either i.v. 1 week before PAC injection or i.p. 3 weeks after to assess their immunomodulatory function on humoral and adaptive immune parameters. Anti-PAC IgM and IgG responses were detected in all PAC-injected rats with a peak at week 2 postinjection and reactivity remaining above baseline levels by week 18. IgG2a and IgG2b were the predominant and long-lasting IgG subtypes. By contrast, no anti-MSC antibody response was detected in the cohort injected with MSC only, but infusion of MSC before PAC injection temporarily augmented the anti-PAC antibody response. Consistent with a cellular immune response to PAC in PAC-injected rats, cytokine/chemokine profiling in serum by antibody array revealed a distinct pattern relative to controls characterized by elevation of multiple markers at week 2, as well as increases in proliferation in draining lymph nodes. Notably, systemic administration of allogeneic MSC under the described conditions did not diminish the immune

  3. Mixed allogeneic chimerism to induce tolerance to solid organ and cellular grafts.

    Science.gov (United States)

    Exner, B G; Acholonu, I N; Bergheim, M; Mueller, Y M; Ildstad, S T

    1999-01-01

    Transplantation of solid organs and cellular grafts has become clinical routine in the last 30 years. However, the requirement for life-long immunosuppression is associated with infections, malignancies and end-organ toxicity. Moreover, the treatment fails to prevent chronic rejection. The induction of donor-specific transplantation tolerance would solve these problems, but has remained an elusive goal. One approach to achieve transplantation tolerance is through hematopoietic chimerism. This review outlines different concepts of hematopoietic chimerism focusing on macrochimerism. Mixed allogeneic chimerism, also known as macrochimerism, is defined as engraftment of hematopoietic stem cells achieved by bone marrow transplantation (BMT). It discusses the advantages and limitations of the BMT as well as approaches to overcome these limitations in the future.

  4. Bone grafting: An overview

    Directory of Open Access Journals (Sweden)

    D. O. Joshi

    2010-08-01

    Full Text Available Bone grafting is the process by which bone is transferred from a source (donor to site (recipient. Due to trauma from accidents by speedy vehicles, falling down from height or gunshot injury particularly in human being, acquired or developmental diseases like rickets, congenital defects like abnormal bone development, wearing out because of age and overuse; lead to bone loss and to replace the loss we need the bone grafting. Osteogenesis, osteoinduction, osteoconduction, mechanical supports are the four basic mechanisms of bone graft. Bone graft can be harvested from the iliac crest, proximal tibia, proximal humerus, proximal femur, ribs and sternum. An ideal bone graft material is biologically inert, source of osteogenic, act as a mechanical support, readily available, easily adaptable in terms of size, shape, length and replaced by the host bone. Except blood, bone is grafted with greater frequency. Bone graft indicated for variety of orthopedic abnormalities, comminuted fractures, delayed unions, non-unions, arthrodesis and osteomyelitis. Bone graft can be harvested from the iliac crest, proximal tibia, proximal humerus, proximal femur, ribs and sternum. By adopting different procedure of graft preservation its antigenicity can be minimized. The concept of bone banking for obtaining bone grafts and implants is very useful for clinical application. Absolute stability require for successful incorporation. Ideal bone graft must possess osteogenic, osteoinductive and osteocon-ductive properties. Cancellous bone graft is superior to cortical bone graft. Usually autologous cancellous bone graft are used as fresh grafts where as allografts are employed as an alloimplant. None of the available type of bone grafts possesses all these properties therefore, a single type of graft cannot be recomm-ended for all types of orthopedic abnormalities. Bone grafts and implants can be selected as per clinical problems, the equipments available and preference of

  5. Resilience in patients after allogeneic stem cell transplantation.

    Science.gov (United States)

    Schumacher, Andrea; Sauerland, Cristina; Silling, Gerda; Berdel, Wolfgang E; Stelljes, Matthias

    2014-02-01

    After undergoing allogeneic stem cell transplantation (alloSCT), patients adapt in very different ways to their taxing situation. Some patients cope very well; others almost seem to fail. Psychosocial variables are important factors for successful reintegration. Besides quality of life, resilience may help to understand the variance in individual differences in adaptation after alloSCT. A pilot study at the University Hospital Muenster, Germany, assessed resilience in patients after alloSCT. The sample included 75 patients (leukemia, lymphoma, myeloma, aplastic anemia) aged 20-76 years. The instruments Resilience Scale RS-25, Hospital Anxiety and Depression Scale, General Self-efficacy Scale, and EORTC QLQ-C30 were used. Resilience is positively correlated with quality of life (Spearman's rho 0.587) and social functioning (0.472), negatively with anxiety (-0.491) and depression (-0.577). Dividing the sample at the median resilience score of 144 reveals that high-resilience patients report less anxiety (p = 0.008) and depression (p resilience patients. No effects on resilience were found for age, gender, and primary disease entity. The high correlation of resilience and self-efficacy (r = 0.698) shows the strong relationship between the two concepts. Our results indicate a potential influence of the time span from alloSCT on patients' resilience. Resilience should be considered as a protective psychosocial factor for patients after alloSCT. A high degree of resilience can help patients to adapt to their situation and to resume their everyday life.

  6. [Allogeneic parathyroid: 2-year follow-up].

    Science.gov (United States)

    Hermosillo-Sandoval, José Manuel; Leonher-Ruezga, Karla Lisseth; Jiménez-Gómez, José Alfredo; Fuentes-Orozco, Clotilde; González-Ojeda, Alejandro; Ramírez-González, Luis Ricardo

    2015-01-01

    Hypoparathyroidism is one of the most frequent complications of neck surgery. The treatment is currently medical; however this involves several complications secondary to high doses of calcium and vitamin D, thus making parathyroid allotransplantation a good management option. Patients with hypoparathyroidism were selected in the April-December period of 2011 in the general surgical clinic. They were between 16 and 65 years, and ingested high doses of calcium. The donors were patients with primary and secondary hyperparathyroidism, and the transplants were performed in relation to blood group and human leucocyte antigen. Five parathyroid allografts were performed. All the patients had iatrogenic hypoparathyroidism, all women with a mean age of 49.8 years. The graft was implanted under local anaesthesia in the non-dominant forearm. Four of the patients are so far considered functional due to the increase in paratohormone, and demonstrating its function by scintigraphy with sestamibi. One of the patients showed no increase in paratohormone or imaging studies that demonstrate its functionality. After a two year follow up the graft remains functional but with with oral calcium intake at a lower dose than before transplantation. None of the patients had immunosuppression side effects. In this study, allogeneic unrelated living parathyroid transplant with an immunosuppressive regimen of six months has proven to be a safe alternative treatment to improve quality of life by decreasing the excessive calcium intake and improving physical activity with adequate graft survival at 24 months follow up. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

  7. The process of natural succession in urban areas

    Science.gov (United States)

    Wayne C. Zipperer

    2011-01-01

    Succession has been a fundamental concept in ecology. Its classical definition is the orderly change in vegetation at a site that is predictable and directional towards a climax state or end point (Clements 1916). A general assumption of succession is that early seres are governed by allogenic processes, environmental processes external to the site, and early seres...

  8. Test of long-term uterine survival after allogeneic transplantation in rabbits.

    Science.gov (United States)

    Saso, Srdjan; Hurst, Simon; Chatterjee, Jayanta; Kuzmin, Eugene; Thum, Yau; David, Anna L; Hakim, Nadey; Corless, David J; Boyd, Michael; Noakes, David E; Lindsay, Iain; Ghaem-Maghami, Sadaf; Del Priore, Giuseppe; Smith, J Richard

    2014-03-01

    To see if: (i) a large vessel aortocaval vascular patch technique may bring about long-term graft survival after allogeneic uterine transplantation (UTn) in a rabbit model; and (ii) fertility can be achieved following natural mating post-allogeneic UTn. Allogeneic uterine cross transplantations were performed in New Zealand white rabbits using an aortocaval macrovascular patch harvested as part of the uterine allograft. Five rabbit recipients received a uterine graft from five unrelated donor rabbits. All female rabbits were unrelated and were of proven fertility with at least one previous litter each. Tacrolimus was administrated for immunosuppression post-transplant. Natural mating was attempted if long-term survival had been achieved. The main outcome measures were: (i) long-term recipient survival; (ii) long-term adequate uterine perfusion; and (iii) successful pregnancy post-UTn. All five recipient animals survived the surgery with satisfactory immediate postoperative recovery. Recipients 1, 2 and 4 died within the first 4 postoperative days. Both long-term survivors failed to conceive following introduction of a proven male breeder despite evidence of mating. Necropsy at 9 and 11 months showed a lack of patency of uterine cornua at the point of anastomosis, albeit a small uterus in recipient 3 and a reddish brown amorphous material at the site of the transplanted uterus in recipient 5. We have demonstrated the feasibility of uterine allotransplantation using a macrovascular patch technique, but could not demonstrate conception because of blocked cornua. To address this, we propose using embryo transfer techniques in order to achieve conception. © 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.

  9. Radiosynoviorthesis in hemophilic arthropathy: pathologic blood pool imaging on pre-therapeutic bone scintigraphy is not a predictor of treatment success

    Energy Technology Data Exchange (ETDEWEB)

    Sabet, Amir [University Duisburg-Essen, Department of Nuclear Medicine, Essen (Germany); University Hospital, Department of Nuclear Medicine, Bonn (Germany); Strauss, Andreas Christian; Schmolders, Jan; Bornemann, Rahel; Pennekamp, Peter Hans [University of Bonn, Department of Orthopaedics and Trauma Surgery, Bonn (Germany); Sabet, Amin; Biersack, Hans Juergen [University Hospital, Department of Nuclear Medicine, Bonn (Germany); Oldenburg, Johannes [University of Bonn, Department of Experimental Hematology and Transfusion Medicine, Bonn (Germany); Ezziddin, Samer [University Duisburg-Essen, Department of Nuclear Medicine, Essen (Germany); Saarland University, Department of Nuclear Medicine, Homburg (Germany)

    2017-03-15

    Increased articular {sup 99m}Tc MDP uptake on blood pool imaging (BPI) of patients with rheumatologic conditions is indicative of active inflammatory changes, and has been suggested as a strong predictor of response to radiosynoviorthesis (RSO). In this study, we aimed to assess the value of pretreatment BPI positivity (i.e. scintigraphic-apparent hyperemia) for successful RSO in hemophilic arthropathy. Thirty-four male patients with painful hemophilic arthropathy underwent RSO after failure of conservative treatment. Treated joints comprised the knee in eight, elbow in five, and ankle in 21 patients. Pretreatment triple-phase bone scintigraphy showed hyperemic joints (pathologic BPI) in 17 patients, whereas 17 patients had no increased tracer uptake on BPI. Response to RSO was evaluated 6 months post-treatment by measuring changes in intensity of arthralgia according to the visual analog scale (VAS), bleeding frequency, and range of motion. The association between hyperemia (pathologic BPI) and treatment outcome was examined using nonparametric tests for independent samples. Clinically evident pain relief occurred in 26 patients (76.5 %), and the mean VAS decreased from 7.7 ± 1.1 to 4.6 ± 2.7 (p < 0.001). Joint bleeding frequency (hemarthrosis) decreased from 4.5 ± 0.6 to 2.1 ± 0.4 during the first 6 months after RSO (p < 0.001). For both parameters (pain relief and bleeding frequency), patients experienced a similar benefit from RSO regardless of pretreatment BPI: arthralgia (p = 0.312) and frequency of hemarthrosis (p = 0.396). No significant improvement was observed for range of motion, but it was significantly more restricted in hyperemic joints both before (p = 0.036) and after treatment (p = 0.022). Hemophilic arthropathy can be effectively treated with RSO regardless of pre-therapeutic BPI. Patients in whom articular hyperemia is not detectable by scintigraphy may have similar (outstanding) outcomes, and thus should not be excluded from treatment. (orig.)

  10. Ready-made allogeneic ABO-specific serum eye drops

    DEFF Research Database (Denmark)

    Harritshøj, Lene Holm; Nielsen, Connie; Ullum, Henrik

    2014-01-01

    PURPOSE: To overcome problems and delays of the preparation of autologous serum eye drops, a production line of ABO-specific allogeneic serum eye drops from male blood donors was set up in a blood bank. Feasibility, clinical routine, safety and efficacy were evaluated in a cohort of patients...... serum treatment. CONCLUSION: Ready-made ABO-identical allogeneic serum eye drops were straightforwardly produced, quality-assured and registered as a safe standard blood product for the treatment of certain cases of severe dry eye disease. Therapeutic efficacy was comparable to previous reports...

  11. Management of the exposure of a dense PTFE (d-PTFE) membrane in guided bone regeneration (GBR): a case report

    OpenAIRE

    GHENSI, P.; STABLUM, W.; BETTIO, E.; SOLDINI, M.C.; TRIPI, T.R.; SOLDINI, C.

    2017-01-01

    Guided bone regeneration (GBR) is a well-established and generally predictable method for repairing alveolar ridge defects and preparing edentulous sites for implant placement. Standard GBR involves filling the space underneath a membrane with autogenous bone or a mixture composed of autogenous bone particles and allogeneic bone tissue or heterologous biomaterials. The use of a barrier membrane for GBR has sometimes been associated with complications, however – reportedly involving exposure, ...

  12. Current Approaches of Bone Morphogenetic Proteins in Dentistry.

    Science.gov (United States)

    Díaz-Sánchez, Rosa-María; Yáñez-Vico, Rosa-María; Fernández-Olavarría, Ana; Mosquera-Pérez, Regina; Iglesias-Linares, Alejandro; Torres-Lagares, Daniel

    2015-06-01

    Bone morphogenic proteins (BMPs) are a group of osteoinductive proteins obtained from nonmineralized bone matrix; they are capable of stimulating the differentiation of pluripotent mesenchymal cells to osteoprogenitor cells. They have become a likely treatment option, given their action on regeneration and remodeling of bone lesions and increasing the bone response around alloplastic materials. It may be feasible in the near future for BMPs to replace autologous and allogenic bone grafts. The application of specific growth factors for osteoinduction without using a bone graft constitutes a real impact on bone regeneration. The use of BMP is not only focused on osteogenic regeneration: There are a variety of studies investigating other properties, such as periodontal or dental regeneration from the conservative viewpoint. In this review, we will highlight the role of the BMP in bone, periodontal and dental regeneration.

  13. A Report of Disseminated Carcinomatosis of the Bone Marrow Originating from Transverse Colon Cancer Successfully Treated with Chemotherapy Using XELOX plus Bevacizumab

    Directory of Open Access Journals (Sweden)

    Masayasu Naito

    2014-07-01

    Full Text Available A 61-year-old male, who had been admitted to another hospital due to disseminated intravascular coagulation (DIC, was referred to our hospital. Total colonoscopy, abdominal dynamic CT and positron-emission tomography revealed bone metastasis and multiple lymphocytic metastases from transverse colon cancer in addition to disseminated carcinomatosis of the bone marrow (DCBM. We immediately performed chemotherapy with XELOX + bevacizumab and denosumab against DCBM from transverse colon cancer in order to avoid radical surgery. In addition, we initiated the administration of recombinant human soluble thrombomodulin for 1 week to treat DIC. The patient was able to tolerate and receive 4 cycles of chemotherapy without any severe side effects. After receiving the 4 cycles of treatment, he recovered from DIC, and the bone and multiple lymphocytic metastases disappeared.

  14. Successful Use of Magnetic Resonance-Guided Focused Ultrasound Surgery for Long-Term Pain Palliation in a Patient Suffering from Metastatic Bone Tumor

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ji Eun; Yoon, Sang Wook; Kim, Kyoung Ah; Lee, Jong Tae [Dept. of Diagnostic Radiology, CHA Bundang Medical Center, CHA University College of Medicine, Seongnam (Korea, Republic of); Shay, Lilach [InSightec. Ltd, Hifa, (Israel); Lee, Kyong Sik [Dept. of General Surgery, CHA Bundang Medical Center, CHA University College of Medicine, Seongnam (Korea, Republic of)

    2011-08-15

    Magnetic Resonance-guided Focused Ultrasound Surgery (MRgFUS) is a clinically effective, non-invasive treatment for thermal ablation of various soft tissue tumors, and is effective in pain palliation following radiation therapy, as has been demonstrated in the initial studies of bone metastases. The current study evaluated the safety and clinical efficacy of MRgFUS for pain palliation prior to radiation therapy, in a patient with a solitary metastatic bone lesion. This is the first case report of MRgFUS treatment with a 1-year follow-up in a patient.

  15. Bone Biopsy

    Science.gov (United States)

    ... Physician Resources Professions Site Index A-Z Bone Biopsy Bone biopsy uses a needle and imaging guidance ... limitations of Bone Biopsy? What is a Bone Biopsy? A bone biopsy is an image-guided procedure ...

  16. In Vivo Immunogenic Response to Allogeneic Mesenchymal Stem Cells and the Role of Preactivated Mesenchymal Stem Cells Cotransplanted with Allogeneic Islets

    Directory of Open Access Journals (Sweden)

    Régis Linhares Oliveira

    2017-01-01

    Full Text Available Mesenchymal stem cells (MSCs are multipotent cells capable of differentiating into cells from the mesenchymal lineage. The hypoimmunogenic characteristic of MSCs has encouraged studies using allogeneic MSCs for the treatment of autoimmune diseases and inflammatory conditions. Promising preclinical results and the safety of allogeneic MSC transplantation have created the possibility of “off-the-shelf” clinical application of allogeneic cells. This study has aimed to evaluate the survival of untreated and IFN-γ- and TNF-α-treated (preactivated allogeneic MSCs transplanted under the kidney capsule of immunocompetent mice together with the role of preactivated MSCs after cotransplantation with allogeneic islets. The preactivation of MSCs upregulated the gene expression of anti-inflammatory molecules and also enhanced their immunomodulatory capacity in vitro. In vivo, allogeneic MSCs provoked an immunogenic response, with the infiltration of inflammatory cells at the transplant site and full graft rejection in both the untreated and preactivated groups. Allogeneic islets cotransplanted with preactivated MSCs prolonged graft survival for about 6 days, compared with islet alone. The present results corroborate the hypothesis that allogeneic MSCs are not immune-privileged and that after playing their therapeutic role they are rejected. Strategies that reduce allogeneic MSC immunogenicity can potentially prolong their in vivo persistence and improve the therapeutic effects.

  17. Single-centre experience of allogeneic haemopoietic stem cell ...

    African Journals Online (AJOL)

    NC 4.0. Single-centre experience of allogeneic haemopoietic stem cell transplant in paediatric patients in Cape Town, South Africa. A van Eyssen,1 MB ChB, DCH (SA), FC Paed (SA), Cert Medical Oncology Paediatrics (SA); N Novitsky,2 FCP ...

  18. Immune Reconstitution after Allogeneic Hematopoietic Cell Transplantation in Children

    NARCIS (Netherlands)

    de Koning, Coco; Plantinga, Maud; Besseling, Paul; Boelens, Jaap Jan; Nierkens, Stefan

    2016-01-01

    Allogeneic (allo) hematopoietic cell transplantation (HCT) has evolved into a potent curative treatment option for a variety of malignant and nonmalignant diseases. The occurrence of complications and mortality after allo-HCT is, however, still high and is strongly associated with immune

  19. Toll-like receptor polymorphisms in allogeneic hematopoietic cell transplantation

    DEFF Research Database (Denmark)

    Kornblit, Brian; Enevold, Christian; Wang, Tao

    2014-01-01

    To assess the impact of the genetic variation in toll-like receptors (TLRs) on outcome after allogeneic myeloablative conditioning hematopoietic cell transplantation (HCT), we investigated 29 single nucleotide polymorphisms across 10 TLRs in 816 patients and donors. Only donor genotype of TLR8 rs...

  20. Soluble urokinase plasminogen activator receptor during allogeneic stem cell transplantation

    DEFF Research Database (Denmark)

    Haastrup, E; Andersen, J; Ostrowski, S R

    2011-01-01

    the course of allogeneic stem cell transplantation (SCT). Twenty SCT patients were included in the study. suPAR was measured by ELISA in daily taken plasma samples during the pretransplant conditioning with chemotherapy and weekly for 1 month after infusion of the graft. suPAR levels before the start...

  1. Sexual function 1-year after allogeneic hematopoietic stem cell transplantation

    DEFF Research Database (Denmark)

    Noerskov, K. H.; Schjødt, I.; Syrjala, K. L.

    2016-01-01

    Treatment with allogeneic hematopoietic stem cell transplantation (HSCT) is associated with short and long-term toxicities that can result in alterations in sexual functioning. The aims of this prospective evaluation were to determine: (1) associations between HSCT and increased sexual dysfunction...

  2. Mesenchymal Stem Cells as a Potent Cell Source for Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Elham Zomorodian

    2012-01-01

    Full Text Available While small bone defects heal spontaneously, large bone defects need surgical intervention for bone transplantation. Autologous bone grafts are the best and safest strategy for bone repair. An alternative method is to use allogenic bone graft. Both methods have limitations, particularly when bone defects are of a critical size. In these cases, bone constructs created by tissue engineering technologies are of utmost importance. Cells are one main component in the manufacture of bone construct. A few cell types, including embryonic stem cells (ESCs, adult osteoblast, and adult stem cells, can be used for this purpose. Mesenchymal stem cells (MSCs, as adult stem cells, possess characteristics that make them good candidate for bone repair. This paper discusses different aspects of MSCs that render them an appropriate cell type for clinical use to promote bone regeneration.

  3. Establishment of banking system for allogeneic cultured dermal substitute.

    Science.gov (United States)

    Kuroyanagi, Yoshimitsu; Kubo, Kentaro; Matsui, Hiromich; Kim, Hyun Jung; Numari, Shinichiro; Mabuchi, Yho; Kagawa, Shizuko

    2004-01-01

    Allogeneic cultured dermal substitute (CDS) was prepared by culturing fibroblasts on a two-layered spongy matrix of hyaluronic acid (HA) and atelo-collagen (Col). Allogeneic CDS can be cryopreserved and transported to other hospitals in a frozen state. Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), platelet derived growth factor (PDGF)-AA, transforming growth factor (TGF)-beta1, keratinocytes growth factor (KGF), interleukin (IL)-6 and IL-8 were contained in the culture medium which was used in preparing CDS over a cultivation period of one week (fresh CDS culture medium sample). After thawing a cryopreserved CDS, the CDS was recultured in a culture medium for one week. VEGF, bFGF, HGF, TGF-beta1 and IL-8 were contained in the culture medium which was used in reculturing CDS for one week (cryopreserved CDS culture medium sample), although some cytokines were detected at a lower level than those before freezing. This finding suggests that the cryopreserved CDS retains its ability to release these cytokines. Clinical research on allogeneic CDS, which was newly developed at the R & D Center for Artificial Skin of Kitasato University, has been carried out in medical centers across Japan with the support of the Millennium Project of the Ministry of Health, Labor and Welfare. It was demonstrated that the allogeneic CDS functions as an excellent cell therapy for intractable skin ulcers as well as burn injuries. The spongy matrix itself, as well as the cytokines released from the allogeneic CDS, seemed to be beneficial for the treatment of intractable skin defect.

  4. Paleo-kinematics of ancient sedimentary sucessions: reading the rock record to disentangle autogenic and allogenic processes (Invited)

    Science.gov (United States)

    Gupta, S.; Paola, C.; Jordan, O.; Sixsmith, P.; Swenson, J. B.; Hampson, G.; Johnson, H.

    2009-12-01

    The sedimentary rock record is a mosaic of depositional units and surfaces that record migration and preservation of depositional and erosional geomorphic elements at geologic timescales. Interrogation of this archive of Earth surface dynamics has largely focussed on deriving the influence of allogenic forcing, with autogenic processes receiving little attention. Whilst much progress has recently been made in examining such interactions from experimental and numerical modelling studies, it has proved difficult to distinguish between such processes from field-based studies of stratigraphic successions. We submit that part of the problem lies in a lack of a rigorous framework with which to describe sedimentary architecture without recourse to model-driven descriptive toolkits. Sedimentary successions represent a record (though likely highly partial) of movements of geomorphic elements in space and time - thus stratigraphy really records the kinematics of net depositional landscapes at long timescales. We propose that depositional units and bounding surfaces can be interpreted as kinematic indicators - indicators of local change in the sedimentary system. Thus a coarsening-up shoreface facies succession is a kinematic indicator of shallowing (local) bathymetry. When such kinematic indicators are spatially and temporally interrogated we can begin to reconstruct the large-scale paleo-kinematics of a sedimentary system, and begin to address issues of allogenic and autogenic processes. In this talk, we describe some examples of reconstructing such paleo-kinematics using outstanding exposures of Cretaceous fluvial to shallow marine rock successions in New Mexico. We illustrate the types of depositional units and surfaces that can be used as paleo-kinematic indicators, and discuss their spatial scaling. We discuss the type of metrics that might usefully inform our understanding of autogenic and allogenic processes from the rock record.

  5. MRI evaluation of a new scaffold-based allogenic chondrocyte implantation for cartilage repair

    Energy Technology Data Exchange (ETDEWEB)

    Dhollander, A.A.M., E-mail: Aad.Dhollander@Ugent.b [Department of Orthopaedic Surgery and Traumatology, Ghent University Hospital, De Pintelaan 185, 1P5, B9000 Gent (Belgium); Huysse, W.C.J., E-mail: Wouter.Huysse@Ugent.b [Department of Radiology, Ghent University Hospital, De Pintelaan 185, -1K12 IB, B9000 Gent (Belgium); Verdonk, P.C.M., E-mail: pverdonk@yahoo.co [Department of Orthopaedic Surgery and Traumatology, Ghent University Hospital, De Pintelaan 185, 1P5, B9000 Gent (Belgium); Verstraete, K.L., E-mail: Koenraad.Verstraete@Ugent.b [Department of Radiology, Ghent University Hospital, De Pintelaan 185, -1K12 IB, B9000 Gent (Belgium); Verdonk, R., E-mail: Rene.Verdonk@Ugent.b [Department of Orthopaedic Surgery and Traumatology, Ghent University Hospital, De Pintelaan 185, 1P5, B9000 Gent (Belgium); Verbruggen, G., E-mail: Gust.Verbruggen@Ugent.b [Laboratory of Connective Tissue Biology, Department of Rheumatology, Ghent University Hospital, De Pintelaan 185, Ghent (Belgium); Almqvist, K.F., E-mail: Fredrik.Almqvist@Ugent.b [Department of Orthopaedic Surgery and Traumatology, Ghent University Hospital, De Pintelaan 185, 1P5, B9000 Gent (Belgium)

    2010-07-15

    Aim: The present study was designed to evaluate the implantation of alginate beads containing human mature allogenic chondrocytes for the treatment of symptomatic cartilage defects of the knee. MRI was used for the morphological analysis of cartilage repair. The correlation between MRI findings and clinical outcome was also studied. Methods: A biodegradable, alginate-based biocompatible scaffold containing human mature allogenic chondrocytes was used for the treatment of symptomatic chondral and osteochondral lesions in the knee. Twenty-one patients were prospectively evaluated with use of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Visual Analogue Scale (VAS) for pain preoperatively and at 3, 6, 9 and 12 months of follow-up. Of the 21 patients, 12 had consented to follow the postoperative MRI evaluation protocol. MRI data were analyzed based on the original MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) and modified MOCART scoring system. The correlation between the clinical outcome and MRI findings was evaluated. Results: A statistically significant clinical improvement became apparent after 6 months and patients continued to improve during the 12 months of follow-up. One of the two MRI scoring systems that were used, showed a statistically significant deterioration of the repair tissue at 1 year of follow-up. Twelve months after the operation complete filling or hypertrophy was found in 41.6%. Bone-marrow edema and effusion were seen in 41.7% and 25% of the study patients, respectively. We did not find a consistent correlation between the MRI criteria and the clinical results. Discussion: The present study confirmed the primary role of MRI in the evaluation of cartilage repair. Two MOCART-based scoring systems were used in a longitudinal fashion and allowed a practical and morphological evaluation of the repair tissue. However, the correlation between clinical outcome and MRI findings was poor. Further

  6. Tackling mantle cell lymphoma (MCL: Potential benefit of allogeneic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Satish Shanbhag

    2010-07-01

    Full Text Available Satish Shanbhag1,2, Mitchell R Smith1, Robert VB Emmons21Department of Medical Oncology, Fox Chase Cancer Center, 2Division of Bone Marrow Transplantation, Temple University, Philadelphia, PA, USAAbstract: Mantle cell lymphoma (MCL is a type of non-Hodgkins lymphoma (NHL associated with poor progression-free and overall survival. There is a high relapse rate with conventional cytotoxic chemotherapy. Intensive combination chemotherapy including rituximab, dose intense CHOP- (cyclophosphamide-doxorubicin-vincristine-prednisone like regimens, high dose cytarabine, and/or consolidation with autologous stem cell transplant (autoSCT have shown promise in significantly prolonging remissions. Data from phase II studies show that even in patients with chemotherapy refractory MCL, allogeneic stem cell transplant (alloSCT can lead to long term disease control. Most patients with MCL are not candidates for myeloablative alloSCT due to their age, comorbidities, and performance status. The advent of less toxic reduced intensity conditioning (RIC regimens, which rely more on the graft-versus-lymphoma (GVL effect, have expanded the population of patients who would be eligible for alloSCT. RIC regimens alter the balance of toxicity and efficacy favoring its use. Treatment decisions are complicated by introduction of novel agents which are attractive options for older, frail patients. Further studies are needed to determine the role and timing of alloSCT in MCL. Currently, for selected fit patients with chemotherapy resistant MCL or those who progress after autoSCT, alloSCT may provide long term survival.Keywords: mantle cell lymphoma, allogeneic SCT, nonmyeloablative, GVL

  7. Management of endocrino-metabolic dysfunctions after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Vantyghem, Marie-Christine; Cornillon, Jérôme; Decanter, Christine; Defrance, Frédérique; Karrouz, Wassila; Leroy, Clara; Le Mapihan, Kristell; Couturier, Marie-Anne; De Berranger, Eva; Hermet, Eric; Maillard, Natacha; Marcais, Ambroise; Francois, Sylvie; Tabrizi, Reza; Yakoub-Agha, Ibrahim

    2014-10-29

    Allogeneic hematopoietic stem cell transplantation is mainly indicated in bone marrow dysfunction related to blood diseases, but also in some rare diseases (adrenoleucodystrophy, mitochondrial neurogastrointestinal encephalomyopathy or MNGIE...). After decades, this treatment has proven to be efficient at the cost of numerous early and delayed side effects such as infection, graft-versus-host disease, cardiovascular complications and secondary malignancies. These complications are mainly related to the conditioning, which requires a powerful chemotherapy associated to total body irradiation (myelo-ablation) or immunosuppression (non myelo-ablation). Among side effects, the endocrine complications may be classified as 1) hormonal endocrine deficiencies (particularly gonado- and somatotropic) related to delayed consequences of chemo- and above all radiotherapy, with their consequences on growth, puberty, bone and fertility); 2) auto-immune diseases, particularly dysthyroidism; 3) secondary tumors involving either endocrine glands (thyroid carcinoma) or dependent on hormonal status (breast cancer, meningioma), favored by immune dysregulation and radiotherapy; 4) metabolic complications, especially steroid-induced diabetes and dyslipidemia with their increased cardio-vascular risk. These complications are intricate. Moreover, hormone replacement therapy can modulate the cardio-vascular or the tumoral risk of patients, already increased by radiotherapy and chemotherapy, especially steroids and anthracyclins... Therefore, patients and families should be informed of these side effects and of the importance of a long-term follow-up requiring a multidisciplinary approach.

  8. Successful Bone Union Following Calcium Phosphate Cement-Assisted Percutaneous Transpedicular Balloon Kyphoplasty of a Large Interbody Cleft on Long-term Hemodialysis Patient.

    Science.gov (United States)

    Ishiguro, Shigeo; Tsujii, Masaya; Sudo, Akihiro

    2011-09-01

    A 68-year-old diabetic man, who had been on dialysis for 3 years, suffered a five week history of severe back pain that was unresponsive to bed rest, analgesics, and bracing. The vertebral cleft formed by an injury gradually increased in size on sequential plain films. Hence, he underwent calcium phosphate cement-assisted percutaneous transpedicular balloon kyphoplasty to treat a painful interbody vacuum cleft. Immediate pain relief and firm bone union were obtained.

  9. Allogenic heart valve bank in the Department of Cardiovascular Surgery and Transplantology of Jagiellonian University in Cracow - 23 years experience in the treatment of aortic valve or aortic root diseases.

    Science.gov (United States)

    Stoliński, J; Marek, G; Marcinkowska, Z; Jaskier, M; Barecka, D; Bartuś, K; Kapelak, B; Sadowski, J; Dziatkowiak, A

    2006-01-01

    Allogenic aortic valves are widely used in case of native aortic valve or root disease as well as failed prosthetic valves with great success. At the Department of Cardiovascular Surgery and Transplantology of the Jagiellonian University in Cracow, aortic valve or aortic root replacement with allogenic aortic valve has been performed for 23 years. Allogenic heart valve bank was founded in 1980. In the bank we prepare both aortic allografts for adult cardiac surgical procedures and pulmonary allografts that are mostly used for repair of congenital heart disease.Allogenic aortic valves implantation was usually considered in our clinic for older patients, patients with infective endocarditis of the native or prosthetic valve, young women in reproductive age and patients with Marfan syndrome. Allografts exhibit excellent clinical performance and acceptable durability with no early failure if properly inserted. Between 1980 and 1992, allografts were obtained only from cadavers during routine autopsies. More than 10% of prepared allografts were exported to other cardiac surgery centres in Poland and foreign countries. Aortic valve replacement using allogenic aortic valves can be performed with acceptable mortality and good long-term results. The procedure although surgically more challenging has the advantage of not requiring anticoagulation therapy, hemodynamic performance of the allogenic valve is excellent, it demonstrates freedom from thromboembolism and infective endocarditis. We would like to emphasize the importance and advantages of the fact that allogenic heart valve bank is placed in the department of cardiovascular surgery and it is able to supply the department in heart valve allografts 24 h a day.

  10. Hemolytic uremic syndrome after bone marrow transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Arai, Ayako; Sakamaki, Hisashi; Tanikawa, Shu [Tokyo Metropolitan Komagome Hospital (Japan)] [and others

    1998-06-01

    One hundred and thirteen patients who underwent autologous or allogeneic bone marrow transplantation (BMT) were investigated for the subsequent development of hemolytic uremic syndrome (HUS). HUS developed in seven patients (four males and three females, five acute lymphocytic leukemia (ALL), one acute myelogenous leukemia, one non-Hodgkin`s lymphoma) between 36-196 days after BMT. Four patients were recipients of autologous BMT and three were those of allogeneic BMT. Six patients were preconditioned with the regimens including fractionated total body irradiation (TBI). ALL and preconditioning regimen with TBI were suspected to be the risk factors for the development of HUS. Cyclosporin A (CSP) administration was discontinued in three patients who had been given CSP for graft-versus-host disease prophylaxis. Predonisolone was given to the three patients and plasma exchange was performed in one patient. Both hemolytic anemia and thrombocytopenia were resolved in virtually all patients, while creatinine elevation has persisted along with hypertension in one patient. (author)

  11. Impact of stem cell source on allogeneic stem cell transplantation outcome in hematological malignancies

    Directory of Open Access Journals (Sweden)

    Stamatović Dragana

    2011-01-01

    Full Text Available Background/Aim. Peripheral blood (PB is used more frequently as a source of stem cells (SCs for allogeneic transplantation. However, the influence of cell source on the clinical outcome of SC transplantation is not yet well established. The aim of this study was to compare the results of PBSC transplantation (PBSCT with bone marrow transplantation (BMT on the basis of engraftment, frequency and severity of immediate (mucositis, acute Graft versus Host Disease - aGvHD and delayed (chronic GvHD - cGvHD complications, as well as transplant-related mortality (TRM, transfusion needs, relapses and overall survival (OS. Methods. We analyzed 158 patients, women/men ratio 64/94 median age 29 (range 9-57, who underwent allogeneic SC transplantation between 1989 and 2009. All included patients had diseases as follows: acute myeloid leukemia (AML - 39, acute lymphoblastic leukemia (ALL - 47, chronic myeloid leukemia (CML - 32, myelodysplastic syndrome (MDS - 10, Hodgkin’s lymphoma (HL - 2, multiple myeloma (MM - 3, granulocytic sarcoma (GrSa - 3, severe aplastic anemia (sAA - 22. The patients underwent transplantations were divided into two groups: BMT group (74 patients and PBSCT group (84 patients. Each recipient had HLA identical sibling donor. SCs from bone marrow were collected by multiple aspirations of iliac bone and from PB by one “Large Volume Leukapheresis” (after recombinant human granulocyte colony stimulating factor, rHuG-CSF application (5-12 μg/kgbm, 5 days. Conditioning regimens were applied according to primary disease, GvHD prophylaxis consisted of combination of a cyclosporine A and methotrexate. Results. Engraftment, according to the count of polymorphonuclear and platelets, were significantly (p < 0.001 faster in the PBSCT vs BMT group. The needs for transfusion support were significantly (p < 0.01 higher in the BMT group. Those patients had more frequently oropharingeal mucositis grade 3/4 (33.3% vs 10.0%, p < 0.05. There were

  12. Desmopressin use for minimising perioperative allogeneic blood transfusion

    Science.gov (United States)

    Carless, Paul A; Stokes, Barrie J; Moxey, Annette J; Henry, David A

    2014-01-01

    Background Public concerns regarding the safety of blood have prompted reconsideration of the use of allogeneic blood (blood from an unrelated donor) transfusion and a range of techniques designed to minimise transfusion requirements. Objectives To examine the efficacy of desmopressin acetate (1-deamino-8-D-arginine-vasopressin) in reducing peri-operative blood loss and the need for red blood cell (RBC) transfusion in patients who do not have congenital bleeding disorders. Search methods We identified studies by searching CENTRAL (The Cochrane Library 2008, Issue 1), MEDLINE (1950 to 2008), EMBASE (1980 to 2008), the Internet (to May 2008), and bibliographies of published articles. Selection criteria Controlled parallel-group trials in which adult patients scheduled for non-urgent surgery were randomised to desmopressin (DDAVP) or to a control group that did not receive DDAVP treatment. Trials were eligible for inclusion if they reported data on the number of patients exposed to allogeneic red cell transfusion or the volume of blood transfused. Data collection and analysis Primary outcomes were: the number of patients exposed to allogeneic red blood cell (RBC) transfusion, and the amount of blood transfused. Other outcomes measured were: blood loss, re-operation for bleeding, post-operative complications (thrombosis, myocardial infarction, stroke), mortality, and length of hospital stay. Treatment effects were pooled using a random-effects model. Main results Nineteen trials that included a total of 1387 patients reported data on the number of patients exposed to allogeneic RBC transfusion. DDAVP did not significantly reduce the risk of exposure to allogeneic RBC transfusion (relative risk (RR) 0.96, 95% confidence interval (CI) 0.87 to 1.06). However, the use of DDAVP significantly reduced total blood loss (weighted mean difference (WMD) −241.78 ml, 95% CI −387.55 to −96.01 ml). Although DDAVP appeared to reduce the overall volume of allogeneic blood

  13. Allogeneic adipose stem cell therapy in acute myocardial infarction.

    Science.gov (United States)

    Rigol, Montserrat; Solanes, Núria; Roura, Santiago; Roqué, Mercè; Novensà, Laura; Dantas, Ana Paula; Martorell, Jaume; Sitges, Marta; Ramírez, José; Bayés-Genís, Antoni; Heras, Magda

    2014-01-01

    Stem cell therapy offers a promising approach to reduce the long-term mortality rate associated with heart failure after acute myocardial infarction (AMI). To date, in vivo translational studies have not yet fully studied the immune response to allogeneic adipose tissue-derived mesenchymal stem cells (ATMSCs). We analysed the immune response and the histological and functional effects of allogeneic ATMSCs in a porcine model of reperfused AMI and determine the effect of administration timing. Pigs that survived AMI (24/26) received intracoronary administration of culture medium after reperfusion (n = 6), ATMSCs after reperfusion (n = 6), culture medium 7 days after AMI (n = 6) or ATMSCs 7 days after AMI (n = 6). At 3-week follow-up, cardiac function, alloantibodies and histological analysis were evaluated. Administration of ATMSCs after reperfusion and 7 days after AMI resulted in similar rates of cell engraftment; some of those cells expressed endothelial, smooth muscle and cardiomyogenic cell lineage markers. Delivery of ATMSCs after reperfusion compared with that performed at 7 days was more effective in increasing: vascular density (249 ± 64 vs. 161 ± 37 vessels/mm2; P < 0.01), T lymphocytes (1 ± 0.4 vs. 0.4 ± 0.3% of area CD3(+) ; P < 0.05) and expression of vascular endothelial growth factor (VEGF; 32 ± 7% vs. 20 ± 4% of area VEGF(+) ; P < 0.01). Allogeneic ATMSC-based therapy did not change ejection fraction but generated alloantibodies. The present study is the first to demonstrate that allogeneic ATMSCs elicit an immune response and, when administered immediately after reperfusion, are more effective in increasing VEGF expression and neovascularization. © 2013 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.

  14. Allogeneic stem cell transplantation in acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Natasha Ali

    2012-11-01

    Full Text Available We report a case series of 12 patients with acute myeloid leukemia who underwent allogeneic stem cell transplant with a matched related donor. Male to female ratio was 1:1. The main complication post-transplant was graft-versus-host disease (n=7 patients. Transplant-related mortality involved one patient; cause of death was multi-organ failure. After a median follow up of 36.0±11.3 months, overall survival was 16%.

  15. Allogeneic red blood cell transfusions: efficacy, risks, alternatives and indications

    OpenAIRE

    Madjdpour, C.; Spahn, D. R.

    2017-01-01

    Careful assessment of risks and benefits has to precede each decision on allogeneic red blood cell (RBC) transfusion. Currently, a number of key issues in transfusion medicine are highly controversial, most importantly the influence of different transfusion thresholds on clinical outcome. The aim of this article is to review current evidence on blood transfusions, to highlight ‘hot topics' with respect to efficacy, outcome and risks, and to provide the reader with transfusion guidelines. In a...

  16. Repair of osteochondral defects with allogeneic tissue engineered cartilage implants.

    Science.gov (United States)

    Schreiber, R E; Ilten-Kirby, B M; Dunkelman, N S; Symons, K T; Rekettye, L M; Willoughby, J; Ratcliffe, A

    1999-10-01

    The objective of this study was to evaluate the effect of allogeneic tissue engineered cartilage implants on healing of osteochondral defects. Rabbit chondrocytes were cultured in monolayer, then seeded onto biodegradable, three-dimensional polyglycolic acid meshes. Cartilage constructs were cultured hydrodynamically to yield tissue with relatively more (mature) or less (immature) hyalinelike cartilage, as compared with adult rabbit articular cartilage. Osteochondral defects in the patellar grooves of both stifle joints either were left untreated or implanted with allogeneic tissue engineered cartilage. Histologic samples from in and around the defect sites were examined 3, 6, 9, and 12, and 24 months after surgery. By 9 months after surgery, defects sites treated with cartilage implants contained significantly greater amounts of hyalinelike cartilage with high levels of proteoglycan, and had a smooth, nonfibrillated articular surface as compared to untreated defects. In contrast, the repair tissue formed in untreated defects had fibrillated articular surfaces, significant amounts of fibrocartilage, and negligible proteoglycan. These differences between treated and untreated defects persisted through 24 months after surgery. The results of this study suggest that the treatment of osteochondral lesions with allogenic tissue engineered cartilage implants may lead to superior repair tissue than that found in untreated osteochondral lesions.

  17. Pulmonary function impairment in patients undergoing allogeneic hematopoietic cell transplantation.

    Science.gov (United States)

    Piesiak, Pawel; Gorczynska, Ewa; Brzecka, Anna; Kosacka, Monika; Jankowska, Renata

    2013-01-01

    Deterioration of pulmonary function can be the sole symptom of early stages of pulmonary complications following allogeneic hematopoietic cells transplantation (alloHCT). The aim of the study was to evaluate the prevalence and types of pulmonary function abnormalities in allogenic cells recipients. Twenty three (5 children and 18 adults) allogeneic hematopoietic cells recipients who underwent pulmonary function assessment before and 6-12 months after alloHCT were included in the study. Forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC), total lung capacity (TLC), and lung diffusion capacity for carbon dioxide (D(L)CO) were determined. Values function impairment before alloHCT: obstructive lung disease (4%), restrictive lung disease (13%), and decreased D(L)CO (17%). In 19 patients (83%) pulmonary function abnormalities were demonstrated after alloHCT. The most common disturbance was a D(L)CO decrease that occurred in 16 patients (70%). In conclusion, frequency of pulmonary function abnormalities in patients after alloHCT is high. A diffusion capacity decrease and restrictive pattern of ventilation insufficiency develop in the majority of patients after alloHCT. It would be reasonable to include pulmonary function testing to standard periodic examination in patients qualified for, and after, alloHCT procedure.

  18. Clinical Allogeneic and Autologous Islet Cell Transplantation: Update

    Directory of Open Access Journals (Sweden)

    Shinichi Matsumoto

    2011-06-01

    Full Text Available Islet cell transplantation is categorized as a β-cell replacement therapy for diabetic patients who lack the ability to secrete insulin. Allogeneic islet cell transplantation is for the treatment of type 1 diabetes, and autologous islet cell transplantation is for the prevention of surgical diabetes after a total pancreatectomy. The issues of allogeneic islet cell transplantation include poor efficacy of islet isolation, the need for multiple donor pancreata, difficulty maintaining insulin independence and undesirable side effects of immunosuppressive drugs. Those issues have been solved step by step and allogeneic islet cell transplantation is almost ready to be the standard therapy. The donor shortage will be the next issue and marginal and/or living donor islet cell transplantation might alleviate the issue. Xeno-islet cell transplantation, β-cell regeneration from human stem cells and gene induction of the naïve pancreas represent the next generation of β-cell replacement therapy. Autologous islet cell transplantation after total pancreatectomy for the treatment of chronic pancreatitis with severe abdominal pain is the standard therapy, even though only limited centers are able to perform this treatment. Remote center autologous islet cell transplantation is an attractive option for hospitals performing total pancreatectomies without the proper islet isolation facilities.

  19. CD56 expression in normal immature granulocytes after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Muroi, Kazuo; Fujiwara, Shin-Ichiro; Tatara, Raine; Sugimoto, Miyuki; Yamamoto, Chihiro; Uehara, Eisuke; Meguro, Akiko; Hatano, Kaoru; Okazuka, Kiyoshi; Oh, Iekuni; Ohmine, Ken; Suzuki, Takahiro; Mori, Masaki; Nagai, Tadashi; Ozawa, Keiya

    2013-01-01

    Bone marrow mononuclear cells from 93 patients with hematological malignancies after allogeneic hematopoietic stem cell transplantation (AHSCT) were analyzed using flow cytometry (FCM). The disease was acute myeloblastic leukemia (50 patients), acute lymphoblastic leukemia, and others. Conditioning was myeloablative (80 patients) or reduced intensity. The stem cell source was bone marrow (75 patients), peripheral blood stem cells, or cord blood. After AHSCT, granulocyte colony-stimulating factor was given to all patients. All patients showed engraftment of the donor cells. FCM was conducted on a median of 22 days after AHSCT. The gate was set around a granulocytic region consisting of immature granulocytes. The positivity rates of CD13, CD14, CD15, CD33, CD34, CD56, and HLA-DR in the cells were 59.9 ± 27.4%, 5.8 ± 8.8%, 98.3 ± 1.9%, 92.3 ± 12.4%, 2.6 ± 5.8%, 24.3 ± 16.7%, and 9.1 ± 6.6%, respectively. The greatest value of CD56 positivity was 73.1%. On the basis of CD56 expression, cases of more than 24% CD56 positivity were assigned to the CD56-high group (39 patients), while the rest were assigned to the CD56-low/negative group. There were no significant differences between the two groups in terms of disease status, sex, donor, hematopoietic stem cells, days of FCM analysis, or peripheral blood cell counts around the days of performing FCM. These results indicate that CD56 can be expressed in normal immature granulocytes at a variety of expression levels in regenerative bone marrow. Attention should be paid when evaluating aberrant antigen expression of CD56 in granulocytes.

  20. Allogeneic hematopoietic SCT performed in non-HEPA filter rooms: initial experience from a single center in India.

    Science.gov (United States)

    Kumar, R; Naithani, R; Mishra, P; Mahapatra, M; Seth, T; Dolai, T K; Bhargava, R; Saxena, R

    2009-01-01

    In developing countries, it is important to ascertain the safety of performing allogeneic hematopoietic SCT (HSCT) in single rooms without high-efficiency particulate air (HEPA) filters. We present our experience of performing 40 such transplants from July 2004 to November 2007. Source of stem cells was peripheral blood in 33, bone marrow in six and combined in one. G-CSF started from day +1. The indications were SAA-18, CML-7, AML-7, ALL-2, myelodysplastic syndrome-2 and thalassemia major-4. The median age was 19 years (range 2.2-46) with 29 male and 11 female participants. Antibacterial and antifungal prophylaxis was administered along with conditioning, and at the onset of fever, systemic antibiotics were started. Antifungal agents were added if fever persisted for 3 days. Median time for neutrophil engraftment was 10 days (range 8-17). Fever occurred in 38 (95%) for a median of 5 days (range 1-38), and blood cultures were positive in seven (17.5%). Systemic antibiotics were used in 95% and antifungals in 57.5% cases. The 30-day mortality was nil, and 100-day mortality was 1 (2.5%). After day 100, there were eight fatalities (20%) due to chronic GVHD-3, relapse-2, graft rejection-2, disseminated tuberculosis and aspergillosis-1. Our experience suggests that allogeneic HSCT can be safely performed in non-HEPA filter rooms in India.

  1. Dose and schedule effect of G-GSF for stem cell mobilization in healthy donors for allogeneic transplantation.

    Science.gov (United States)

    Kröger, Nicolaus; Zander, Axel R

    2002-07-01

    In the present review, we analyze the literature regarding the dose and schedule effects of granulocyte stimulating factor (G-CSF) for stem cell mobilization of healthy donors for allogeneic stem cell transplantation. There is now evidence for a dose and schedule dependency of G-CSF in mobilizing peripheral blood progenitor cells (PBSC) in healthy donors for allogeneic stem cell transplantation. In general, a dose between 10 and 16 microg/kg split into two doses is recommended. Leukapheresis should be performed on day 4 or 5. A higher dose of G-CSF might be appropriate in donors with low CD34+ baseline cell count (< 2000/ml) or if a high CD34+ cell number is required. However, a higher dose of G-CSF results in a higher acute toxicity like bone and muscle pain or headache. Severe adverse events like thromboembolic events, cerebrovascular incidents, anaphylactoid reactions and an atraumatic splenic rupture have been rarely reported. A prolonged follow-up of the donors is needed to rule out late toxicity of the donors.

  2. Autoserum: An Optimal Supplement for Bone Marrow Mesenchymal Stem Cells of Liver-Injured Rats

    Directory of Open Access Journals (Sweden)

    Qinglin Zhang

    2015-01-01

    Full Text Available Mesenchymal stem cells (MSCs are an attractive source for the clinical cell therapy of liver injury. Although the use of adult serum, platelet lysate, or cord blood serum solves some of the problems caused by fetal bovine serum (FBS, the allogeneic immune response, contamination, and donor-to-donor and donor-to-receptor differences still obstruct the application of MSCs. In this study, the influences of autoserum from liver-injured rats (LIRs and allogeneic serum from healthy rats on the isolation and culture of bone marrow MSCs (BMSCs were examined and compared to FBS. The results showed that BMSCs cultured with autoserum or allogeneic serum exhibited better MSC-specific morphology, lower rate of cell senescent, and higher proliferation kinetics than those with FBS. In addition, autoserum promoted the osteogenic differentiation potential of BMSCs as allogeneic serum did. Although there were no significant differences in proliferation activity, immunophenotypic characterization, and differentiation potential between BMSCs cultured with autoserum and those with allogeneic serum, the potential adverse immunological reactions in patients with allogeneic material transplantation must be considered. We therefore believe that the autoserum from liver-injured patients may be a better choice for MSC expansion to meet the needs of liver injury therapy.

  3. Hemorrhagic cystitis after allogeneic hematopoietic stem cell transplants is the complex result of BK virus infection, preparative regimen intensity and donor type.

    Science.gov (United States)

    Silva, Leandro de Padua; Patah, Poliana A; Saliba, Rima M; Szewczyk, Nicholas A; Gilman, Lisa; Neumann, Joyce; Han, Xiang-Yang; Tarrand, Jeffrey; Ribeiro, Rachel; Gulbis, Alison; Shpall, Elizabeth J; Jones, Roy; Popat, Uday; Walker, Julia A; Petropoulos, Demetrios; Chiattone, Alexandre; Stewart, John; El-Zimaity, Maha; Anderlini, Paolo; Giralt, Sergio; Champlin, Richard E; de Lima, Marcos

    2010-07-01

    Hemorrhagic cystitis is a common cause of morbidity after allogeneic stem cell transplantation, frequently associated with BK virus infection. We hypothesized that patients with positive BK viruria before unrelated or mismatched related donor allogeneic hematopoietic stem cell transplantation have a higher incidence of hemorrhagic cystitis. To test this hypothesis, we prospectively studied 209 patients (median age 49 years, range 19-71) with hematologic malignancies who received bone marrow (n=78), peripheral blood (n=108) or umbilical cord blood (n=23) allogeneic hematopoietic stem cell transplantation after myeloablative (n=110) or reduced intensity conditioning (n=99). Donors were unrelated (n=201) or haploidentical related (n=8). Twenty-five patients developed hemorrhagic cystitis. Pre-transplant BK viruria detected by quantitative PCR was positive in 96 patients. The one-year cumulative incidence of hemorrhagic cystitis was 16% in the PCR-positive group versus 9% in the PCR-negative group (P=0.1). The use of umbilical cord blood or a haploidentical donor was the only significant predictor of the incidence of hemorrhagic cystitis on univariate analysis. There was also a trend for a higher incidence after myeloablative conditioning. Multivariate analysis showed that patients who had a positive PCR pre-transplant and received haploidentical or cord blood grafts with myeloablative conditioning had a significantly higher risk of developing hemorrhagic cystitis (58%) than all other recipients (7%, PHemorrhagic cystitis is the result of a complex interaction of donor type, preparative regimen intensity, and BK viruria.

  4. [Etiopathogenesis of aplastic anemia and of the severe form treated with immunosuppression and bone marrow transplantation].

    Science.gov (United States)

    Dulley, F L; Lotério, H A; Massumoto, C M; Llacer, P E; Chamone, D de A

    1989-01-01

    Aplastic anemia is a condition characterized by bone marrow hipoplasia and pancytopenia. Various etiologic agents are related to the acquired form of this disease but in many cases the causative agents remain obscure. Severe aplastic anemia has been treated by immunosuppression and allogeneic marrow transplantation.

  5. Bone grafts and biomaterials substitutes for bone defect repair: A review

    Directory of Open Access Journals (Sweden)

    Wenhao Wang

    2017-12-01

    Full Text Available Bone grafts have been predominated used to treat bone defects, delayed union or non-union, and spinal fusion in orthopaedic clinically for a period of time, despite the emergency of synthetic bone graft substitutes. Nevertheless, the integration of allogeneic grafts and synthetic substitutes with host bone was found jeopardized in long-term follow-up studies. Hence, the enhancement of osteointegration of these grafts and substitutes with host bone is considerably important. To address this problem, addition of various growth factors, such as bone morphogenetic proteins (BMPs, parathyroid hormone (PTH and platelet rich plasma (PRP, into structural allografts and synthetic substitutes have been considered. Although clinical applications of these factors have exhibited good bone formation, their further application was limited due to high cost and potential adverse side effects. Alternatively, bioinorganic ions such as magnesium, strontium and zinc are considered as alternative of osteogenic biological factors. Hence, this paper aims to review the currently available bone grafts and bone substitutes as well as the biological and bio-inorganic factors for the treatments of bone defect.

  6. Monitoring of a new approach of immunotherapy with allogenic {sup 111}In-labelled NK cells in patients with renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Meller, Birgit; Lauer, Isabel; Schelper, Lutz F.; Hof, Katharina von; Richter, Eckart; Baehre, Manfred [Clinic of Radiotherapy and Nuclear Medicine, University of Luebeck, Ratzeburger Allee 160, 23538, Luebeck (Germany); Frohn, Christoph; Brand, Joerg-Matthias; Kirchner, Holger [Institute of Immunology and Transfusion Medicine, University of Luebeck, Ratzeburger Allee 160, 23538, Luebeck (Germany)

    2004-03-01

    The transfusion of allogenic, in vitro expanded natural killer cells (NKC) is a novel therapy option in oncology. To date, however, the biodistribution and kinetics of allogenic NKC have not been investigated. Therefore, in this study three patients with renal cell carcinoma received 3-7 x 10{sup 8} NKC labelled with indium-111 oxine with a tenfold excess of unlabelled cells during NKC therapy. Whole-body scintigrams were obtained (0.5-144 h) in the anterior and posterior views. Scintigrams were analysed using a region of interest technique, and single-photon emission tomography (SPET) studies of the abdomen were performed. Results were compared to those obtained with polymerase chain reaction (PCR) of the peripheral blood (determination of foreign DNA, nested PCR, limit of detection 0.01%). Shortly after transfusion of NKC, more than 50% of the activity was accumulated in the lungs. We observed redistribution effects from lungs to liver, spleen and bone marrow. No significant loss of activity could be detected. In two of four large metastases, tracer accumulation could be proven by SPET. As confirmed by scintigrams and PCR, the fraction of circulating transfused cells was low at all times. Long-term activity retention might be caused either by survival of the allogenic cells, as confirmed by PCR (up to 3 days p.i.), or by phagocytosis of labelled cellular fragments. However, PCR data and uptake in metastases indicated long survival of a portion of allogenic NKC. Such long survival and low retention of the cells in the lung are requirements for an effective immunotherapeutic approach. (orig.)

  7. Repair of long bone defects with demineralized bone matrix and autogenous bone composite

    Directory of Open Access Journals (Sweden)

    Mehmet T Ozdemir

    2011-01-01

    Full Text Available Background: Repair of diaphyseal bone defects is a challenging problem for orthopedic surgeons. In large bone defects the quantity of harvested autogenous bone may not be sufficient to fill the gap and then the use of synthetic or allogenic grafts along with autogenous bone becomes mandatory to achieve compact filling. Finding the optimal graft mixture for treatment of large diaphyseal defects is an important goal in contemporary orthopedics and this was the main focus of this study. The aim of this study is to investigate the efficacy of demineralized bone matrix (DBM and autogenous cancellous bone (ACB graft composite in a rabbit bilateral ulna segmental defect model. Materials and Methods: Twenty-seven adult female rabbits were divided into five groups. A two-centimeter piece of long bone on the midshaft of the ulna was osteotomized and removed from the rabbits′ forearms. In group 1 (n=7 the defects were treated with ACB, in group 2 (n=7 with DBM, and in group 3 (n=7 with ACB and DBM in the ratio of 1:1. Groups 4 and 5, with three rabbits in each group, were the negative and positive controls, respectively. Twelve weeks after implantation the rabbits were sacrificed and union was evaluated with radiograph (Faxitron, dual-energy x-ray absorptiometry (DEXA, and histological methods (decalcified sectioning. Results: Union rates and the volume of new bone in the different groups were as follows: group 1 - 92.8% union and 78.6% new bone; group 2 - 72.2% union and 63.6% new bone; and group 3 - 100% union and 100% new bone. DEXA results (bone mineral density [BMD] were as follows: group 1 - 0.164 g/cm 2 , group 2 - 0.138 g/cm 2 , and group 3 - 0.194 g/cm 2 . Conclusions: DBM serves as a graft extender or enhancer for autogenous graft and decreases the need of autogenous bone graft in the treatment of bone defects. In this study, the DBM and ACB composite facilitated the healing process. The union rate was better with the combination than with the

  8. Beneficial effects of non-matched allogeneic cord blood mononuclear cells upon patients with idiopathic osteoporosis

    Directory of Open Access Journals (Sweden)

    Li Jun

    2012-05-01

    Full Text Available Abstract Background Immunological arguments and historical examples have shown that treatment with cord blood for non-hematopoietic activities, such as growth factor production and stimulation of angiogenesis, may not require matching or immune suppression. Methods To study the benefit of blood mononuclear cell therapy, 8 patients with idiopathic osteoporosis were given intermittent treatments with non-matched allogeneic cord blood mononuclear cells for 3 months. Morning fasting samples were collected for measuring urine N telopeptide of type-1 collagen, serum bone-specific alkaline phosphatase, and insulin-like growth factor 1 during one-year study. Results Clinical response was striking. Serum insulin-like growth factor 1 significantly increased in all patients at 3 months compared with baseline values, from 264.1 ± 107.0 to 384.4 ± 63.1 ng/mL (P = 0.002, with a tendency to return to baseline values at 12 months (312.9 ± 75.5 ng/mL, P = 0.083. In contrast, differences in serum bone-specific alkaline phosphatase and urine N telopeptide of type-1 collagen were not significant at 3 (P = 0.765, P = 0.057 or 12 months (P = 0.889, P = 0.122. A beneficial effect on bone density was observed in all patients at the lumbar spine. The mean bone mineral density calculated during therapy (0.6811 ± 0.1442 g/cm2 tended higher than baseline values (0.6239 ± 0.1362 g/cm2, P  Conclusions The findings indicate that for these patients with idiopathic osteoporosis, treatment with cord blood mononuclear cells led to a significant increase in insulin-like growth factor 1 levels, which favors the increase in bone mineral density.

  9. Intractable Diseases Treated with Intra-Bone Marrow-Bone Marrow Transplantation

    Directory of Open Access Journals (Sweden)

    Ming eLi

    2014-09-01

    Full Text Available Bone marrow transplantation (BMT is used to treat hematological disorders, autoimmune diseases and lymphoid cancers. Intra bone marrow-BMT (IBM-BMT has been proven to be a powerful strategy for allogeneic BMT due to the rapid hematopoietic recovery and the complete restoration of T cell functions. IBM-BMT not only replaces hematopoietic stem cells but also mesenchymal stem cells (MSMCs. MSMCs are multi-potent stem cells that can be isolated from bone marrow, umbilical cord blood, and adipose tissue. MSMCs play an important role in the support of hematopoiesis, and modify and influence the innate and adaptive immune systems. MSMCs also differentiate into mesodermal, endodermal and ectodermal lineage cells to repair tissues. This review aims to summarize the functions of bone marrow-derived- MSMCs, and the treatment of intractable diseases such as rheumatoid arthritis and malignant tumors with IBM-BMT.

  10. Enhanced in utero allogeneic engraftment in mice after mobilizing fetal HSCs by α4β1/7 inhibition.

    Science.gov (United States)

    Kim, Aimee G; Vrecenak, Jesse D; Boelig, Matthew M; Eissenberg, Linda; Rettig, Michael P; Riley, John S; Holt, Matthew S; Conner, Michael A; Loukogeorgakis, Stavros P; Li, Haiying; DiPersio, John F; Flake, Alan W; Peranteau, William H

    2016-11-17

    In utero hematopoietic cell transplantation (IUHCT) is a novel nonmyeloablative approach that results in donor-specific tolerance and mixed allogeneic chimerism. Clinical application is limited by low levels of donor cell engraftment. Competition from endogenous hematopoietic stem cells (HSCs) for limited "space" in fetal hematopoietic organs remains a significant barrier to successful IUHCT. AMD3100, a CXCR4 inhibitor, and firategrast, an α4β1 and α4β7 integrin inhibitor (α4β1/7), have been shown to disrupt HSC retention in the postnatal hematopoietic niche. We hypothesized that maternal administration of AMD3100 and/or firategrast prior to IUHCT would mobilize endogenous HSCs from the fetal liver (FL) and result in preferential FL homing of donor HSCs and enhanced long-term engraftment following IUHCT in an allogeneic mouse model. We demonstrate that (1) both agents cross the placenta with rapidly detectable fetal serum concentrations following maternal administration; (2) firategrast treatment alone or with AMD3100 mobilizes endogenous HSCs from the FL and results in increased FL homing of donor HSCs following IUHCT; and (3) enhanced donor HSC homing following firategrast treatment translates into increased long-term multilineage donor cell engraftment. This approach highlights the potential of mobilization strategies to overcome barriers to successful engraftment and increase the clinical promise of IUHCT. © 2016 by The American Society of Hematology.

  11. Effect of storage on osteoinductive properties of demineralized bone in rats

    DEFF Research Database (Denmark)

    Pinholt, E M; Solheim, E

    1994-01-01

    A requirement for the clinical use of demineralized bone is the possibility of storing the material without loss of its osteoinductive properties. Seventy-five 8-week-old male Wistar rats were randomly assigned to one of five groups of 15 rats each. Lyophilized demineralized allogeneic bone...... uptake of the recovered implants. Storage for 9 months at both temperatures did not affect the osteoinduction, whereas storage for 14 months at both temperatures led to a statistically significant decrease in osteoinduction....

  12. Bone Diseases

    Science.gov (United States)

    ... need to get enough calcium, vitamin D, and exercise. You should also avoid smoking and drinking too much alcohol. Bone diseases can make bones easy to break. Different kinds of bone problems include Low bone density and osteoporosis, which make your bones weak and ...

  13. Impact of posttransplantation G-CSF on outcomes of allogeneic hematopoietic stem cell transplantation

    Science.gov (United States)

    Khoury, Hanna J.; Loberiza, Fausto R.; Ringdén, Olle; Barrett, A. John; Bolwell, Brian J.; Cahn, Jean-Yves; Champlin, Richard E.; Gale, Robert Peter; Hale, Gregory A.; Urbano-Ispizua, Alvaro; Martino, Rodrigo; McCarthy, Philip L.; Tiberghien, Pierre; Verdonck, Leo F.; Horowitz, Mary M.

    2006-01-01

    Granulocyte colony-stimulating factor (G-CSF) is often administered after hematopoietic-cell transplantation (HCT) to accelerate neutrophil recovery, but it is unclear what impact G-CSF has on long-term transplantation outcomes. We analyzed within the database of the Center for International Blood and Marrow Transplant Research the impact of giving posttransplantation G-CSF on the outcomes of allogeneic HCT for acute myelogenous leukemia and chronic myelogenous leukemia in 2719 patients who underwent transplantation between 1995 and 2000. These included 1435 recipients of HLA-identical sibling bone marrow (BM), 609 recipients of HLA-identical peripheral-blood stem cells (PBSCs), and 675 recipients of unrelated donor BM transplants. Outcomes were compared between patients receiving or not receiving G-CSF within 7 days of HCT according to graft type. Median follow-up was more than 30 months (range, 2-87 months). G-CSF shortened the posttransplantation neutropenic period, but did not affect days +30 and +100 treatment-related mortality (TRM). Probabilities of acute and chronic graft-versus-host disease (GVHD), leukemia-free survival (LFS), and overall survival were similar whether or not G-CSF was given. Multivariate analyses confirmed that giving G-CSF did not affect the risk of GVHD, TRM, LFS, or survival. In conclusion, results of this study found no long-term benefit or disadvantage of giving G-CSF after transplantation to promote hematopoietic recovery. PMID:16239431

  14. Donor Selection for Allogenic Hemopoietic Stem Cell Transplantation: Clinical and Ethical Considerations

    Directory of Open Access Journals (Sweden)

    Irene Riezzo

    2017-01-01

    Full Text Available Allogenic hematopoietic progenitor cell transplantation (allo-HSCT is an established treatment for many diseases. Stem cells may be obtained from different sources: mobilized peripheral blood stem cells, bone marrow, and umbilical cord blood. The progress in transplantation procedures, the establishment of experienced transplant centres, and the creation of unrelated adult donor registries and cord blood banks gave those without an human leucocyte antigen- (HLA- identical sibling donor the opportunity to find a donor and cord blood units worldwide. HSCT imposes operative cautions so that the entire donation/transplantation procedure is safe for both donors and recipients; it carries with it significant clinical, moral, and ethical concerns, mostly when donors are minors. The following points have been stressed: the donation should be excluded when excessive risks for the donor are reasonable, donors must receive an accurate information regarding eventual adverse events and health burden for the donors themselves, a valid consent is required, and the recipient’s risks must be outweighed by the expected benefits. The issue of conflict of interest, when the same physician has the responsibility for both donor selection and recipient care, is highlighted as well as the need of an adequate insurance protection for all the parties involved.

  15. Outcomes of allogeneic hematopoietic cell transplantation in patients with dyskeratosis congenita.

    Science.gov (United States)

    Gadalla, Shahinaz M; Sales-Bonfim, Carmem; Carreras, Jeanette; Alter, Blanche P; Antin, Joseph H; Ayas, Mouhab; Bodhi, Prasad; Davis, Jeffrey; Davies, Stella M; Deconinck, Eric; Deeg, H Joachim; Duerst, Reggie E; Fasth, Anders; Ghavamzadeh, Ardeshir; Giri, Neelam; Goldman, Frederick D; Kolb, E Anders; Krance, Robert; Kurtzberg, Joanne; Leung, Wing H; Srivastava, Alok; Or, Reuven; Richman, Carol M; Rosenberg, Philip S; Toledo Codina, Jose Sanchez de; Shenoy, Shalini; Socié, Gerard; Tolar, Jakub; Williams, Kirsten M; Eapen, Mary; Savage, Sharon A

    2013-08-01

    We describe outcomes after allogeneic transplantation in 34 patients with dyskeratosis congenita who underwent transplantation between 1981 and 2009. The median age at transplantation was 13 years (range, 2 to 35). Approximately 50% of transplantations were from related donors. Bone marrow was the predominant source of stem cells (24 of 34). The day-28 probability of neutrophil recovery was 73% and the day-100 platelet recovery was 72%. The day-100 probability of grade II to IV acute GVHD and the 3-year probability of chronic graft-versus-host disease were 24% and 37%, respectively. The 10-year probability of survival was 30%; 14 patients were alive at last follow-up. Ten deaths occurred within 4 months from transplantation because of graft failure (n = 6) or other transplantation-related complications; 9 of these patients had undergone transplantation from mismatched related or from unrelated donors. Another 10 deaths occurred after 4 months; 6 of them occurred more than 5 years after transplantation, and 4 of these were attributed to pulmonary failure. Transplantation regimen intensity and transplantations from mismatched related or unrelated donors were associated with early mortality. Transplantation of grafts from HLA-matched siblings with cyclophosphamide-containing nonradiation regimens was associated with early low toxicity. Late mortality was attributed mainly to pulmonary complications and likely related to the underlying disease. Copyright © 2013 American Society for Blood and Marrow Transplantation. All rights reserved.

  16. Acquisition and Cure of Autoimmune Disease Following Allogeneic Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Hsin-An Hou

    2007-09-01

    Full Text Available Hematopoietic stem cell transplantation (HSCT can either cause or eliminate autoimmune disease. Here, we report two cases. One was a 33-year-old woman with myelodysplastic syndrome (refractory anemia who received bone marrow transplantation from her human leukocyte antigen (HLA-identical sister who had a history of Graves' disease. Antithyroid antibodies, including antimicrosomal antibody and antithy-roglobulin antibody, appeared 4 months after transplantation. Clinical hyperthyroidism appeared 7 months after transplantation, and a hypothyroid state was noted 2 months later. The other case was a 50-year-old woman with Sjögren's syndrome and hypothyroidism who was diagnosed with peripheral T cell non-Hodgkin's lymphoma. She received allogeneic peripheral blood stem cell transplantation (PBSCT from her histocompatible sister owing to only partial response to traditional chemotherapy. Cure of lymphoma and remission of Sjögren's syndrome was noted 4 years after PBSCT. These two illustrative cases, one of acquisition of hyperthyroidism and the other of remission of Sjögren's syndrome after transplantation, highlights that HSCT can induce adoptive autoimmune disease or cure coincidental autoimmune disease. Donor selection and attentive monitoring is required in such circumstances.

  17. Allogeneic hematopoietic stem cell transplantation in children with primary immunodeficiencies: Hospital Israelita Albert Einstein experience.

    Science.gov (United States)

    Fernandes, Juliana Folloni; Kerbauy, Fabio Rodrigues; Ribeiro, Andreza Alice Feitosa; Kutner, Jose Mauro; Camargo, Luis Fernando Aranha; Stape, Adalberto; Troster, Eduardo Juan; Zamperlini-Netto, Gabriele; Azambuja, Alessandra Milani Prandini de; Carvalho, Bruna; Dorna, Mayra de Barros; Vilela, Marluce Dos Santos; Jacob, Cristina Miuki Abe; Costa-Carvalho, Beatriz Tavares; Cunha, Jose Marcos; Carneiro-Sampaio, Magda Maria; Hamerschlak, Nelson

    2011-06-01

    To report the experience of a tertiary care hospital with allogeneic hematopoietic stem cell transplantation in children with primary immunodeficiencies. Seven pediatric patients with primary immunodeficiencies (severe combined immunodeficiency: n = 2; combined immunodeficiency: n = 1; chronic granulomatous disease: n = 1; hyper-IgM syndrome: n = 2; and IPEX syndrome: n = 1) who underwent eight hematopoietic stem cell transplants in a single center, from 2007 to 2010, were studied. Two patients received transplants from HLA-identical siblings; the other six transplants were done with unrelated donors (bone marrow: n = 1; cord blood: n = 5). All patients had pre-existing infections before hematopoietic stem cell transplants. One patient received only anti-thymocyte globulin prior to transplant, three transplants were done with reduced intensity conditioning regimens and four transplants were done after myeloablative therapy. Two patients were not evaluated for engraftment due to early death. Three patients engrafted, two had primary graft failure and one received a second transplant with posterior engraftment. Two patients died of regimen related toxicity (hepatic sinusoidal obstruction syndrome); one patient died of progressive respiratory failure due to Parainfluenza infection present prior to transplant. Four patients are alive and well from 60 days to 14 months after transplant. Patients' status prior to transplant is the most important risk factor on the outcome of hematopoietic stem cell transplants in the treatment of these diseases. Early diagnosis and the possibility of a faster referral of these patients for treatment in reference centers may substantially improve their survival and quality of life.

  18. Ethylene oxide gas sterilization does not reduce the osteoinductive potential of demineralized bone in rats

    DEFF Research Database (Denmark)

    Solheim, E; Pinholt, E M; Bang, G

    1995-01-01

    It has been shown that different sterilization procedures of demineralized bone may influence its osteoinductive properties. The aim of this study was to evaluate the effect of ethylene oxide sterilization for 1, 3, and 6 hours on the osteoinductive potential of allogeneic demineralized bone...... without prior sterilization of the material, whereas the demineralized bone implanted in Groups B, C, and D had been sterilized in ethylene oxide gas for 1, 3, or 6 hours, respectively, and aerated for 48 hours. At 4 weeks postoperatively, bone formation was evaluated quantitatively by strontium 85 uptake...

  19. Bone Metastasis

    Science.gov (United States)

    ... help reduce pain and other symptoms of bone metastases. Symptoms Sometimes, bone metastasis causes no signs and ... cancers most likely to cause bone metastasis include: Breast cancer Kidney cancer Lung cancer Lymphoma Multiple myeloma Prostate ...

  20. Bone Cancer

    Science.gov (United States)

    Cancer that starts in a bone is uncommon. Cancer that has spread to the bone from another ... more common. There are three types of bone cancer: Osteosarcoma - occurs most often between ages 10 and ...

  1. Analysis of the results of replacement of large bone defects in the patients who underwent segmental bone resection for tumor

    Science.gov (United States)

    Anastasieva, E. A.; Voropaeva, A. A.; Sadovoy, M. A.; Kirilova, I. A.

    2017-09-01

    The problem of large bone defects replacement, formed after segmental bone resections, remains an actual issue of modern orthopedics. It is known that the autograft is the most acceptable material for the replacement of bone tissue; however, due to its small volume and physical properties, it has limited usage. Our goal is to analyze the results of the experiments and studies on replacement of large bone defects after resection of the bone tumor. The problem is justified by the complicated osteoconduction and osteointegration; because it is proved that the reconstruction of the microcirculatory bloodstream is difficult in the presence of damage more than 4 cm2. It was revealed that using of allograft in combination with additional components is comparable in effectiveness, including long-term period, with autograft usage. It is promising to combine plastic allogenous material, capable of reconstructing defects of various configuration intraoperatively, with the necessary chemotherapy with controlled desorption to maintain effective concentration of drug.

  2. Endocrinopathies after Allogeneic and Autologous Transplantation of Hematopoietic Stem Cells

    Directory of Open Access Journals (Sweden)

    Francesco Orio

    2014-01-01

    Full Text Available Early and late endocrine disorders are among the most common complications in survivors after hematopoietic allogeneic- (allo- and autologous- (auto- stem cell transplant (HSCT. This review summarizes main endocrine disorders reported in literature and observed in our center as consequence of auto- and allo-HSCT and outlines current options for their management. Gonadal impairment has been found early in approximately two-thirds of auto- and allo-HSCT patients: 90–99% of women and 60–90% of men. Dysfunctions of the hypothalamus-pituitary-growth hormone/insulin growth factor-I axis, hypothalamus-pituitary-thyroid axis, and hypothalamus-pituitary-adrenal axis were documented as later complicances, occurring in about 10, 30, and 40–50% of transplanted patients, respectively. Moreover, overt or subclinical thyroid complications (including persistent low-T3 syndrome, chronic thyroiditis, subclinical hypo- or hyperthyroidism, and thyroid carcinoma, gonadal failure, and adrenal insufficiency may persist many years after HSCT. Our analysis further provides evidence that main recognized risk factors for endocrine complications after HSCT are the underlying disease, previous pretransplant therapies, the age at HSCT, gender, total body irradiation, posttransplant derangement of immune system, and in the allogeneic setting, the presence of graft-versus-host disease requiring prolonged steroid treatment. Early identification of endocrine complications can greatly improve the quality of life of long-term survivors after HSCT.

  3. Mimicking the nanostructure of bone matrix to regenerate bone

    Science.gov (United States)

    Kane, Robert; Ma1, Peter X.

    2014-01-01

    Key features of bone tissue structure and composition are capable of directing cellular behavior towards the generation of new bone tissue. Bone tissue, as well as materials derived from bone, have a long and successful history of use as bone grafting materials. Recent developments in design and processing of synthetic scaffolding systems has allowed the replication of the bone’s desirable biological activity in easy to fabricate polymeric materials with nano-scale features exposed on the surface. The biological response to these new tissue-engineering scaffold materials oftentimes exceeds that seen on scaffolds produced using biological materials. PMID:24688283

  4. Comparison of bone regeneration using three demineralized freeze-dried bone allografts: A histological and histomorphometric study in rabbit calvaria

    Directory of Open Access Journals (Sweden)

    Parichehr Behfarnia

    2012-01-01

    Conclusion: Both test and control groups resulted in successful new bone formation. No difference was noted in bone formation and remained particles between three commercial bone allografts. Further studies in this issue may be needed.

  5. Inflammatory response to the administration of mesenchymal stem cells in an equine experimental model: effect of autologous, and single and repeat doses of pooled allogeneic cells in healthy joints.

    Science.gov (United States)

    Ardanaz, N; Vázquez, F J; Romero, A; Remacha, A R; Barrachina, L; Sanz, A; Ranera, B; Vitoria, A; Albareda, J; Prades, M; Zaragoza, P; Martín-Burriel, I; Rodellar, C

    2016-03-31

    Mesenchymal stem cells (MSCs) transplantation has become a promising therapeutic choice for musculoskeletal injuries. Joint-related disorders are highly prevalent in horses. Therefore, these animals are considered as suitable models for testing MSC-based therapies for these diseases. The aim of this study was to investigate the clinical and inflammatory responses to intra-articular single and repeat dose administration of autologous or of pooled allogeneic MSCs in healthy equine healthy joints. Six horses were intra-articularly injected with a single autologous dose of bone marrow derived MSCs (BM-MSCs) and two separate doses of allogeneic BM-MSCs pooled from several donors. All contralateral joints were injected with Lactated Ringer's Solution (LRS) as the control vehicle. Signs of synovitis and lameness were evaluated at days 0, 1, 2, 3, 5 and 10 after injection. Total protein (TP), white blood cell count (WBC) and neutrophil count (NC) in synovial fluid were also measured at the same time-points. A mild synovial effusion without associated lameness was observed after all BM-MSCs injections. The second allogeneic injection caused the lowest signs of synovitis. Local temperature slightly increased after all BM-MSCs treatments compared to the controls. TP, WBC and NC in synovial fluids also increased during days 1 to 5 after all BM-MSCs injections. Both, clinical and synovial parameters were progressively normalized and by day 10 post-inoculation appeared indistinguishable from controls. Intra-articular administration of an allogeneic pool of BM-MSCs represents a safe therapeutic strategy to enhance MSCs availability. Importantly, the absence of hypersensitivity response to the second allogeneic BM-MSCs injection validates the use of repeat dose treatments to potentiate the therapeutic benefit of these cells. These results notably contribute to the development of stem cell based therapies for equine and human joint diseases.

  6. Bone regeneration during distraction osteogenesis.

    Science.gov (United States)

    Amir, Lisa R; Everts, Vincent; Bronckers, Antonius L J J

    2009-07-01

    Bone has the capacity to regenerate in response to injury. During distraction osteogenesis, the renewal of bone is enhanced by gradual stretching of the soft connective tissues in the gap area between two separated bone segments. This procedure has received much clinical attention as a way to correct congenital growth retardation of bone tissue or to generate bone to fill skeletal defects. The process of bone regeneration involves a complex system of biological changes whereby mechanical stress is converted into a cascade of signals that activate cellular behavior resulting in (enhanced) formation of bone. Over the last decade, significant progress has been made in understanding the bone regeneration process during distraction osteogenesis. The mechanical and biological factors that are important for the success of the distraction treatment have been partially characterized and are discussed in this review.

  7. Use and preservation methods of bone grafts in small animals

    Directory of Open Access Journals (Sweden)

    Rafael Garabet Agopian

    2016-09-01

    Full Text Available http://dx.doi.org/10.5007/2175-7925.2016v29n3p11 The present review describes the main characteristics of bone grafts used in small animals. Bone grafts are tissues without vasculature, which facilitate the production of new bone cells with osteogenic and osteoinductive factors that lead to the differentiation of cells and structural support for bone marrow. The transplant of a graft is followed by three stages: osteogenesis, or the formation of new bone; osteoinduction, which is the differentiation of cells; and osteoconduction, the process of growth of mesenchymal cells and capillaries that results in new bone formation. The composition of bone grafts may include spongy bone, cortical bone, cortical-spongy bone, cartilage or bone marrow. Grafts can also be classified according to their origin, being autogenous tissue when they are transplanted from the same individual, allogenous (homologous when originating from another individual of the same species, and xenogenous when obtained from a different species.

  8. Successful DNA Profiling for Identification of burnt Families from their bones using AmpFℓSTR Identifiler® Plus Kit

    Directory of Open Access Journals (Sweden)

    Muhamamd Shahzad

    2016-02-01

    Full Text Available Background: DNA profiling plays a vital role in the identification of dead bodies during mass disasters. Severe fragmentation, decomposition, burning and intermixing of the remains can occur in the mass disasters. DNA analysis faces many challenges especially when the dead bodies are completely decomposed or burnt. This report presents the identification of 32 completely burnt individuals including three families from their remains in a bus using AmpFlSTR Identifiler Plus® Kit and AmpFlSTR Y-filer® Kit. Methods: DNA was extracted from provided remains of burnt bodies and reference samples by organic extraction procedure. The extracted quantity of DNA was calculated on ABI SDS7500 real time PCR with Quantifiler® Human DNA Quantification Kit (Applied Biosystems. DNA samples of 32 completely burnt individuals including three families were amplified using AmpFlSTR Identifiler Plus® Kit and AmpFlSTR Y-filer® Kit. The genotyping of these amplified samples was performed on ABI 3130xl Genetic Analyzer. Results: The resulting data obtained from Genetic Analyzer was analyzed using GeneMapper ID software version 3.2 (Applied Biosystems. Seventeen burnt individuals including 3 burnt families were identified with the help of 16 autosomal STRs and 6 were identified through Y-STR analysis by allele sharing of their provided reference samples of parents and brothers respectively. Conclusion: For the identification of unknown individuals particularly burnt deceased victims, STR analysis has become the gold standard in forensic science. Successful DNA profiling through the amplification of STR markers of AmpFlSTR Identifiler Plus® Kit proved to be very helpful in identifying the remains of burnt individuals even in the presence of inhibition observed in the Real Time PCR.

  9. Allogeneic CD19-CAR-T cell infusion after allogeneic hematopoietic stem cell transplantation in B cell malignancies

    Directory of Open Access Journals (Sweden)

    Jun Liu

    2017-01-01

    Full Text Available Abstract Background Allogeneic hematopoietic stem cell transplantation (allo-HSCT is considered the cornerstone in treatment of hematological malignancies. However, relapse of the hematological disease after allo-HSCT remains a challenge and is associated with poor long-term survival. Chimeric antigen receptor redirected T cells (CAR-T cells can lead to disease remission in patients with relapsed/refractory hematological malignancies. However, the therapeutic window for infusion of CAR-T cells post allo-HSCT and its efficacy are debatable. Main body In this review, we first discuss the use of CAR-T cells for relapsed cases after allo-HSCT. We then review the toxicities and the occurrence of graft-versus-host disease in relapsed patients who received CAR-T cells post allo-HSCT. Finally, we review clinical trial registrations and the therapeutic time window for infusion of CAR-T cells post allo-HSCT. Conclusions The treatment of allogeneic CAR-T cells is beneficial for patients with relapsed B cell malignancies after allo-HSCT with low toxicities and complications. However, multicenter clinical trials with larger sample sizes should be performed to select the optimal therapeutic window and confirm its efficacy.

  10. Autogenous femoral head as grafting material for mandibular augmentation

    NARCIS (Netherlands)

    Vos, M. D.; Raghoebar, G. M.; van der Wal, J. E.; Kalk, W. W. I.; Vissink, A.

    2009-01-01

    Bone grafting is commonly used for augmentation of the atrophic edentulous maxilla and mandible. Although bone substitutes and allogeneic frozen bone grafts have been applied successfully, fresh autogenous bone grafts remain the 'gold standard' in maxillofacial reconstructive surgery. A disadvantage

  11. Tracking intracavernously injected adipose-derived stem cells to bone marrow.

    Science.gov (United States)

    Lin, G; Qiu, X; Fandel, T; Banie, L; Wang, G; Lue, T F; Lin, C-S

    2011-01-01

    The intracavernous (i.c.) injection of stem cells (SCs) has been shown to improve erectile function in various erectile dysfunction (ED) animal models. However, the tissue distribution of the injected cells remains unknown. In this study we tracked i.c.-injected adipose-derived stem cells (ADSCs) in various tissues. Rat paratesticular fat was processed for ADSC isolation and culture. The animals were then subject to cavernous nerve (CN) crush injury or sham operation, followed by i.c. injection of 1 million autologous or allogeneic ADSCs that were labeled with 5-ethynyl-2-deoxyuridine (EdU). Another group of rats received i.c. injection of EdU-labeled allogeneic penile smooth muscle cells (PSMCs). At 2 and 7 days post injection, penises and femoral bone marrow were processed for histological analyses. Whole femoral bone marrows were also analyzed for EdU-positive cells by flow cytometry. The results show that ADSCs exited the penis within days of i.c. injection and migrated preferentially to bone marrow. Allogenicity did not affect the bone marrow appearance of ADSCs at either 2 or 7 days, whereas CN injury reduced the number of ADSCs in bone marrow significantly at 7 but not 2 days. The significance of these results in relation to SC therapy for ED is discussed.

  12. Tracking Intracavernously Injected Adipose-Derived Stem Cells to Bone Marrow

    Science.gov (United States)

    Lin, Guiting; Qiu, Xuefeng; Fandel, Thomas; Banie, Lia; Wang, Guifang; Lue, Tom F.; Lin, Ching-Shwun

    2012-01-01

    Intracavernous (IC) injection of stem cells (SCs) has been shown to improve erectile function in various erectile dysfunction (ED) animal models. However, the tissue distribution of the injected cells remains unknown. In this study we tracked IC injected adipose-derived stem cells (ADSCs) in various tissues. Rat paratesticular fat was processed for ADSC isolation and culture. The animals were then subject to cavernous nerve (CN) crush injury or sham operation, followed by IC injection of one million autologous or allogeneic ADSCs that were labeled with 5-ethynyl-2-deoxyuridine (EdU). Another group of rats received IC injection of EdU-labeled allogeneic penile smooth muscle cells (PSMCs). At 2 and 7 days post-injection, penises and femoral bone marrow were processed for histological analyses. Whole femoral bone marrows were also analyzed for EdU-positive cells by flow cytometry. The results show that ADSCs exited the penis within days of IC injection and migrated preferentially to bone marrow. Allogenicity did not affect ADSC's bone marrow appearance either at 2 or 7 days, while CN injury reduced the number of ADSCs in bone marrow significantly at 7 but not 2 days. The significance of these results in relation to SC therapy for ED is discussed. PMID:21796145

  13. Bioactivity And Bone Formation In Silicon-Substituted Hydroxyapatite

    Directory of Open Access Journals (Sweden)

    Ulvan Ozad

    2012-06-01

    Full Text Available Bioactivity and successful bone formation in silicon-substituted hydroxyapatite bone grafts were investigated by using scanning electron microscopy and electron dispersive x-ray spectroscopy. Areas of bone formation have been detected in scanning electron microscopy; and, arranged lamellar collagen has been observed. 20.8% average carbon content rise has been detected between bone graft and the produced bone; and, this has been confirmed to be a gradual increase throughout the interphase. Obvious bone formation and maturation were observed in the samples. Carbon content gradually increased from bone graft to the bone formed, confirming formation of new bone and dissociation of silicon-substituted bone graft.

  14. Allogeneic corneoscleral limbus tissue transplantation for treatment of the necrosis in porphyria eye disease

    Directory of Open Access Journals (Sweden)

    Feng Yan

    2014-08-01

    Full Text Available Porphyria cutanea tarda (PCT with ocular complications are rarely reported. To the best of our knowledge, no reports exist on allogeneic corneoscleral limbus tissue transplantation for treatment of these. Amniotic membrane grafting had been performed in their patient suffering from porphyria eye disease, but necrosis developed in the grafts. Nevertheless, in our patient, allogeneic corneoscleral limbus transplantation prevented necrosis from development at corneoscleral limbus. So we considered that the allogeneic corneoscleral limbus transplantation might be an option to repair the necrosis in porphyria eye disease with avoiding sunlight and using artificial tear drops.

  15. Ethical problems in bone marrow transplantation in children.

    Science.gov (United States)

    Massimo, L

    1996-11-01

    The medical staff caring for children with hematological or oncological diseases is often faced with delicate ethical and, at times, legal problems. Although many of these are common to other branches of pediatrics where patients are children lacking decision-making capacity, others, such as bone marrow transplantation (BMT), are peculiar to this specialty. This is a vanguard treatment for a wide range of diseases that are either incurable or resistant to conventional therapies. If the patient does not have a related donor, ethical and legal problems can occur: profound emotional dilemmas arise both because of the fretful search for a donor and because of the limited period the patient can be transplanted with good expectations of success. National and International Registries are linked to all BMT Units for the identification of compatible donors with the recipient. Hospitals hosting a BMT Unit must fulfill several requirements which are crucial to guaranteeing the best results when faced with the complexity and aggressiveness of transplantation and possible complications, such as a blood bank, an infectious diseases department, a rehabilitation unit, the availability of consultants, as well as playworkers, teachers, psychologists and social workers. Any trial carried out in a Center without sufficient experience, simply pleading the concept of "last hope" is not ethical, even considering possible late effects and sequelae. For allogeneic bone marrow transplantation it is necessary to obtain both the Consent of the donor and the Consent of parents of the recipient. Often the donor is a child sibling of the patient, lacking decision-making capacity as well. Information to parents of both children must be detailed. In reality, there are practically no risks for the child donor and, if any, they are linked to the general anaesthesia. The text of the Informed Consent is usually deliberated and accepted in advance by the Ethics Committee of the Institution where the

  16. A Previous Miscarriage and a Previous Successful Pregnancy Have a Different Impact on HLA Antibody Formation during a Subsequent Successful Pregnancy

    NARCIS (Netherlands)

    Geneugelijk, Kirsten; Hönger, Gideon; van Deutekom, Hanneke Wilhelmina Maria; Hösli, Irene Mathilde; Schaub, Stefan; Spierings, Eric

    2016-01-01

    Inherited paternal HLA antigens from the semi-allogeneic fetus may trigger maternal immune responses during pregnancy, leading to the production of child-specific HLA antibodies. The prevalence of these HLA antibodies increases with the number of successful pregnancies. In the present study, we

  17. A Previous Miscarriage and a Previous Successful Pregnancy Have a Different Impact on HLA Antibody Formation during a Subsequent Successful Pregnancy

    OpenAIRE

    Kirsten Geneugelijk; Gideon Hönger; Hanneke Wilhelmina Maria van Deutekom; Irene Mathilde Hoesli; Stefan Schaub; Eric Spierings

    2016-01-01

    Inherited paternal HLA antigens from the semi-allogeneic fetus may trigger maternal immune responses during pregnancy, leading to the production of child-specific HLA antibodies. The prevalence of these HLA antibodies increases with the number of successful pregnancies. In the present study, we investigated the effect of a single prior miscarriage on HLA antibody formation during a subsequent successful pregnancy. Women with a successful pregnancy with one or more prior miscarriages (n = 229)...

  18. Outcome of allogeneic hematopoietic stem cell transplantation for childhood acute lymphoblastic leukemia in second complete remission: a single institution study

    Directory of Open Access Journals (Sweden)

    Eun-Jung Lee

    2012-03-01

    Full Text Available Purpose : The survival rate for childhood acute lymphoblastic leukemia (ALL has improved significantly. However, overall prognosis for the 20 to 25% of patients who relapse is poor, and allogeneic hematopoietic stem cell transplantation (HSCT offers the best chance for cure. In this study, we identified significant prognostic variables by analyzing the outcomes of allogeneic HSCT in ALL patients in second complete remission (CR. Methods : Fifty-three ALL patients (42 men, 79% who received HSCT in second CR from August 1991 to February 2009 were included (26 sibling donor HSCTs, 49%; 42 bone marrow transplantations, 79%. Study endpoints included cumulative incidence of acute and chronic graft-versus-host disease (GVHD, relapse, 1-year transplant-related mortality (TRM, disease-free survival (DFS, and overall survival (OS. Results : Cumulative incidences of acute GVHD (grade 2 or above and chronic GVHD were 45.3% and 28.5%, respectively. The estimated 5-year DFS and OS for the cohort was 45.2¡?#?.8%; and 48.3¡?#?%,; respectively. Only donor type, i.e., sibling versus unrelated, showed significant correlation with DFS in multivariate analysis (P=0.010. The rates of relapse and 1 year TRM were 28.9¡?#?.4%; and 26.4¡?#?.1%;, respectively, and unrelated donor HSCT (P=0.002 and HLA mismatch (P =0.022 were significantly correlated with increased TRM in univariate analysis. Conclusion : In this single institution study spanning more than 17 years, sibling donor HSCT was the only factor predicting a favorable result in multivariate analysis, possibly due to increased TRM resulting from unrelated donor HSCT.

  19. Risk factors of Ganciclovir-related neutropenia after allogeneic stem cell transplantation: a retrospective monocentre study on 547 patients.

    Science.gov (United States)

    Venton, G; Crocchiolo, R; Fürst, S; Granata, A; Oudin, C; Faucher, C; Coso, D; Bouabdallah, R; Berger, P; Vey, N; Ladaique, P; Chabannon, C; le Merlin, M; Blaise, D; El-Cheikh, J

    2014-02-01

    Cytomegalovirus (CMV) infection is a serious complication that may occur in the weeks or months following bone marrow transplantation. However, both Ganciclovir and the CMV infection itself can cause marrow toxicity, notably neutropenia, that may consequently expose these immunosuppressed patients to life-threatening bacterial and/or fungal infections. The aim of this retrospective study was to identify factors associated with the occurrence of grade III-IV neutropenia among patients receiving pre-emptive Ganciclovir therapy after allogeneic stem cell transplantation at our Institution. We identified 547 consecutive patients transplanted from January 2005 to June 2011 at our Institution. In all, 190 patients (35%) presented with CMV reactivation of whom 30 patients (5%) were excluded from the analysis because they already had neutropenia at the time of reactivation. Finally, 160 (29%) patients were analysed. According to multivariate analysis, at the time of treatment initiation, the risk factors significantly associated with a grade III-IV Ganciclovir-related neutropenia included a high viral load (hazard ratio (HR) = 2.68, 95% CI 1.25-5.737, p 0.01); an absolute neutrophil count >3000 was a protective factor (HR = 0.26, 95% CI 0.125-0.545, p 2 mg/dL was associated with higher Ganciclovir-related neutropenia (HR = 2.4, 95% CI 1.11-5.17, p 0.002). This large analysis revealed three risk factors for Ganciclovir-related neutropenia among patients with CMV reactivation after allogeneic stem cell transplantation; prompt identification of patients at risk when antiviral therapy is started may allow clinicians to adopt adequate preventive measures, so reducing the morbidity and mortality associated with CMV reactivation. © 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.

  20. CD4+ Regulatory T Cells Generated in Vitro with IFN-γ and Allogeneic APC Inhibit Transplant Arteriosclerosis

    Science.gov (United States)

    Warnecke, Gregor; Feng, Gang; Goto, Ryoichi; Nadig, Satish N.; Francis, Ross; Wood, Kathryn J.; Bushell, Andrew

    2010-01-01

    We have developed a method to generate alloreactive regulatory T cells in vitro in the presence of interferon (IFN)-γ and donor antigen presenting cells (APCs). We hypothesized that these IFN-γ–conditioned T cells (Tcon) would reduce transplantation-associated arteriosclerosis. Tcon were generated from mouse (CBA.Ca, H-2k) CD4+ T cells cultured in the presence of IFN-γ for 14 days. These cultures were pulsed with bone marrow–derived B6 (H-2b) APC. 1 × 105 CD25−CD4+ effector T cells from naive H-2k mice were then cotransferred with 4 × 105 Tcon into CBA-rag−/− mice. One day later, these mice received a fully allogenic B6 CD31−/− abdominal aorta transplant. Transfer of CD25−CD4+ effectors resulted in 29.7 ± 14.5% luminal occlusion of allogeneic aortic grafts after 30 days. Cotransfer of Tcon reduced this occlusion to 11.7 ± 13.1%; P < 0.05. In addition, the CD31− donor endothelium was fully repopulated by CD31+ recipient endothelial cells in the absence of Tcon, but not in the presence of Tcon. In some experiments, we cotransplanted B6 skin with aortic grafts to ensure enhanced reactivation of the regulatory cells, which led to an additional reduction in vasculopathy (1.9 ± 3.0% luminal occlusion). In the presence of Tcon, CD4+ T cell infiltration into grafts was markedly reduced by a regulatory mechanism that included reduced priming and proliferation of CD25−CD4+ effectors. These data illustrate the potential of ex vivo generated regulatory T cells for the inhibition of transplant-associated vasculopathy. PMID:20472892

  1. Allogeneic transplantation for multiple myeloma: late relapse may occur as localised lytic lesion/plasmacytoma despite ongoing molecular remission.

    Science.gov (United States)

    Byrne, J L; Fairbairn, J; Davy, B; Carter, I G; Bessell, E M; Russell, N H

    2003-02-01

    Allogeneic SCT for myeloma may be curative for young patients, but its role remains controversial because of a reported high TRM in some series. Since 1991, we have performed 25 allografts for myeloma using fully matched sibling donors. Of the 18 evaluable patients, 13 achieved CR at a median time of 2.5 months post-transplant. The five patients who were not in CR when assessed at 3 months received a short course of alpha-interferon and four subsequently achieved CR with this approach at a median of 82 days. One patient who failed to respond to IFN went on to achieve CR after four doses of DLI therapy, thus giving an overall CR rate of 72%. Seven patients have relapsed at a median of 4.7 years post-transplant (range 1.38-7.7 years) including two patients who had received IFN therapy. In five of these cases, relapse has been as a localised area of bone disease or isolated plasmacytoma with no evidence of marrow involvement by trephine biopsy or molecular analysis. All patients with localised relapse were treated with local radiotherapy +/-DLI and four are currently disease free despite two patients having had further treatment for a second localised lesion. Six patients died of TRM (24%) and the OS at 8 years is currently 69% with an EFS of 26%. These results suggest that allogeneic SCT for myeloma can be carried out with an acceptable TRM and a high CR rate. However, late relapses as localised disease may be a frequent finding and may represent foci of myeloma not eradicated by the conditioning. The use of pretransplant MRI scanning and top-up radiotherapy to involved areas may be useful in preventing this type of relapse.

  2. Bone marrow aspiration

    Science.gov (United States)

    Iliac crest tap; Sternal tap; Leukemia - bone marrow aspiration; Aplastic anemia - bone marrow aspiration; Myelodysplastic syndrome - bone marrow aspiration; Thrombocytopenia - bone marrow aspiration; Myelofibrosis - bone marrow aspiration

  3. Multi-scale osteointegration and neovascularization of biphasic calcium phosphate bone scaffolds

    Science.gov (United States)

    Lan, Sheeny K.

    Bone grafts are utilized clinically to guide tissue regeneration. Autologous bone and allogeneic bone are the current clinical standards. However, there are significant limitations to their use. To address the need for alternatives to autograft and allograft, researchers have worked to develop synthetic grafts, also referred to as scaffolds. Despite extensive efforts in this area, a gap persists between basic research and clinical application. In particular, solutions for repairing critical size and/or load-bearing defects are lacking. The aim of this thesis work was to address two critical barriers preventing design of successful tissue engineering constructs for bone regeneration within critical size and/or load-bearing defects. Those barriers are insufficient osteointegration and slow neovascularization. In this work, the effects of scaffold microporosity, recombinant human bone morphogenetic protein-2 delivery and endothelial colony forming cell vasculogenesis were evaluated in the context of bone formation in vivo. This was accomplished to better understand the role of these factors in bone regeneration, which may translate to improvements in tissue engineering construct design. Biphasic calcium phosphate (BCP) scaffolds with controlled macro- and microporosity were implanted in porcine mandibular defects. Evaluation of the BCP scaffolds after in vivo implantation showed, for the first time, osteocytes embedded in bone within scaffold micropores (regenerating bone and this has significant implications with regard to improved scaffold mechanical properties. The presence of osteocytes within scaffold micropores is an indication of scaffold osteoinductivity because a chemotactic factor must be present to induce cell migration into pores on the order of the cell diameter. It is likely that the scaffold undergoes in vivo modifications involving formation of a biological apatite layer within scaffold micropores and possibly co-precipitation of endogenous

  4. Immune Reconstitution after Allogeneic Hematopoietic Stem Cell Transplantation

    Science.gov (United States)

    Ogonek, Justyna; Kralj Juric, Mateja; Ghimire, Sakhila; Varanasi, Pavankumar Reddy; Holler, Ernst; Greinix, Hildegard; Weissinger, Eva

    2016-01-01

    The timely reconstitution and regain of function of a donor-derived immune system is of utmost importance for the recovery and long-term survival of patients after allogeneic hematopoietic stem cell transplantation (HSCT). Of note, new developments such as umbilical cord blood or haploidentical grafts were associated with prolonged immunodeficiency due to delayed immune reconstitution, raising the need for better understanding and enhancing the process of immune reconstitution and finding strategies to further optimize these transplant procedures. Immune reconstitution post-HSCT occurs in several phases, innate immunity being the first to regain function. The slow T cell reconstitution is regarded as primarily responsible for deleterious infections with latent viruses or fungi, occurrence of graft-versus-host disease, and relapse. Here we aim to summarize the major steps of the adaptive immune reconstitution and will discuss the importance of immune balance in patients after HSCT. PMID:27909435

  5. Allogeneic H-2 antigen expression is insufficient for tumor rejection.

    Science.gov (United States)

    Cole, G A; Cole, G A; Clements, V K; Garcia, E P; Ostrand-Rosenberg, S

    1987-12-01

    Murine A strain (KkDdLd) sarcoma I (SaI) tumor cells have been transfected with a cloned H-2Kb gene. The resulting clones (SKB clones) stably express high levels of a molecule that is serologically and biochemically indistinguishable from the H-2Kb antigen. SKB clones are not susceptible to cytotoxic T lymphocyte-mediated lysis by H-2Kb-specific bulk, cloned, or H-2Kb-restricted lymphocytic choriomeningitis virus-specific effectors. Survival times of A/J and B10.A mice challenged i.p. with the H-2Kb-expressing transfectants and the parental SaI cells are similar, suggesting that the presence of an allogeneic major histocompatibility complex class I antigen on the surface of this tumor line is insufficient for tumor rejection.

  6. Allogeneic cell therapy bioprocess economics and optimization: downstream processing decisions.

    Science.gov (United States)

    Hassan, Sally; Simaria, Ana S; Varadaraju, Hemanthram; Gupta, Siddharth; Warren, Kim; Farid, Suzanne S

    2015-01-01

    To develop a decisional tool to identify the most cost effective process flowsheets for allogeneic cell therapies across a range of production scales. A bioprocess economics and optimization tool was built to assess competing cell expansion and downstream processing (DSP) technologies. Tangential flow filtration was generally more cost-effective for the lower cells/lot achieved in planar technologies and fluidized bed centrifugation became the only feasible option for handling large bioreactor outputs. DSP bottlenecks were observed at large commercial lot sizes requiring multiple large bioreactors. The DSP contribution to the cost of goods/dose ranged between 20-55%, and 50-80% for planar and bioreactor flowsheets, respectively. This analysis can facilitate early decision-making during process development.

  7. Allogeneic hematopoietic stem-cell transplantation for leukocyte adhesion deficiency

    DEFF Research Database (Denmark)

    Qasim, Waseem; Cavazzana-Calvo, Marina; Davies, E Graham

    2009-01-01

    OBJECTIVES: Leukocyte adhesion deficiency is a rare primary immune disorder caused by defects of the CD18 beta-integrin molecule on immune cells. The condition usually presents in early infancy and is characterized by deep tissue infections, leukocytosis with impaired formation of pus, and delayed...... wound healing. Allogeneic hematopoietic stem-cell transplantation offers the possibility of curative therapy, and with patient numbers at any individual center being limited, we surveyed the transplant experience at 14 centers worldwide. METHODS: The course of 36 children with a confirmed diagnosis...... of leukocyte adhesion deficiency who underwent hematopoietic stem-cell transplantation between 1993 and 2007 was retrospectively analyzed. Data were collected by the registries of the European Society for Immunodeficiencies/European Group for Blood and Marrow Transplantation, and the Center for International...

  8. Low Bone Density

    Science.gov (United States)

    ... Density Exam/Testing › Low Bone Density Low Bone Density Low bone density is when your bone density ... people with normal bone density. Detecting Low Bone Density A bone density test will determine whether you ...

  9. Dynamics of bone graft healing around implants

    Directory of Open Access Journals (Sweden)

    Narayan Venkataraman

    2015-01-01

    A few questions arise pertaining to the use of bone grafts along with implants are whether these are successful in approximation with implant. Do they accelerate bone regeneration? Are all defects ultimately regenerated with new viable bone? Is the bone graft completely resorbed or integrated in new bone? Does the implant surface characteristic positively affect osseointegration when used with a bone graft? What type of graft and implant surface can be used that will have a positive effect on the healing type and time? Finally, what are the dynamics of bone graft healing around an implant? This review discusses the cellular and molecular mechanisms of bone graft healing in general and in vicinity of another foreign, avascular body, namely the implant surface, and further, the role of bone grafts in osseointegration and/or clinical success of the implants.

  10. Allogeneic serum eye drops for the treatment of persistent corneal epithelial defect

    National Research Council Canada - National Science Library

    Chiang, C-C; Chen, W-L; Lin, J-M; Tsai, Y-Y

    2009-01-01

    .... If the epithelial defect was healing, the allogenic serum was gradually tapered. If the epithelial defect remained nearly the same size at day 14, amniotic membrane transplantation (AMT) was performed...

  11. Clinical Trials Using Adenovirus/Cytomegalovirus/Epstein-Barr Virus-specific Allogeneic Cytotoxic T Lymphocytes

    Science.gov (United States)

    NCI supports clinical trials that test new and more effective ways to treat cancer. Find clinical trials studying adenovirus/cytomegalovirus/epstein-barr virus-specific allogeneic cytotoxic t lymphocytes.

  12. Comparison of immune reconstitution after allogeneic vs. autologous stem cell transplantation in 182 pediatric recipients

    Directory of Open Access Journals (Sweden)

    V. Wiegering

    2017-03-01

    Conclusion: Children undergoing a HSCT show a different pattern of immune reconstitution in the allogeneic and autologous setting. This might influence the outcome and should affect the clinical handling of infectious prophylaxis and re-vaccinations.

  13. Allogeneic epidermal substitutes in the treatment of chronic diabetic leg and foot ulcers

    Directory of Open Access Journals (Sweden)

    Andrea Marchesi

    2014-09-01

    Full Text Available Aim: Diabetic foot ulcers are the most common cause of nontraumatic lower extremity amputations in the industrialized world. Tissue-engineering products offer a lower extremity salvage strategy when healing does not proceed according to the standard of care. New allogeneic sheets are available for the management of diabetic leg and foot ulcers. Methods: The endpoints of this case series study regard preliminary outcomes of the application of allogeneic keratinocytes composed of benzyl ester of hyaluronic acid to 16 diabetic foot and leg ulcers in 11 patients with type 2 diabetes mellitus. Results: Between 21 and 70 days after cellular therapy, 6 out of 16 lesions were completely healed, reducing the wound dimension by 70% and improving the wound bed score by 52%. Conclusion: The clinical results of the new allogeneic sheets indicate that allogeneic keratinocytes may represent an effective and safe therapy for diabetic foot and leg ulcers in the multidisciplinary approach to this diabetes-related complication.

  14. Differential effect of conditioning regimens on cytokine responses during allogeneic stem cell transplantation

    DEFF Research Database (Denmark)

    Andersen, J; Heilmann, C; Jacobsen, N

    2006-01-01

    The purpose of this study was to characterize cytokine responses during conditioning in patients undergoing allogeneic stem cell transplantation (SCT) with the aim to identify which markers that may reliably reflect inflammatory activity during conditioning. We investigated inflammatory and anti...

  15. Establishing an autologous versus allogeneic hematopoietic cell transplant program in nations with emerging economies.

    Science.gov (United States)

    Chaudhri, Naeem A; Aljurf, Mahmoud; Almohareb, Fahad I; Alzahrani, Hazzaa A; Bashir, Qaiser; Savani, Bipin; Gupta, Vikas; Hashmi, Shahrukh K

    2017-12-01

    More than 70,000 hematopoietic cell transplants are currently performed each year, and these continue to increase every year. However, there is a significant variation in the number of absolute transplants and transplant rates between centers, countries, and global regions. The prospect for emerging countries to develop a hematopoietic cell transplantation (HCT) program, as well as to decide on whether autologous HCT (auto-HCT) or allogeneic HCT (allo-HCT) should be established to start with, relies heavily on factors that can explain differences between these two procedures. Major factors that will influence a decision about establishing the type of HCT program are macroeconomic factors such as organization of the healthcare network, available resources and infrastructure. Prevalence of specific diseases in the region as well genetic background of donors and recipients will also influence the mandate or priority of the HCT in the national healthcare plan to explain some of the country-specific differences. Furthermore, microeconomic factors play a role, such as center-specific experience in treating various disorders requiring hematopoietic stem cell transplantation, along with accreditation status and patient volume. The objective of the transplant procedure was to improve the survival and quality of life of patients. The regional difference that one notices in emerging countries about the higher number of allo-HCT compared with auto-HCT procedures performed is primarily based on suboptimal healthcare network in treating various malignant disorders that are the primary indication for auto-stem cell transplantation. In this context, nonmalignant disorders such as bone marrow failure syndromes, inherited genetic disorders and hemoglobinopathies have become the major indication for stem cell transplantation. Better understanding of these factors will assist in establishing new transplant centers in the emerging countries to achieve their specific objectives and

  16. Fetal liver-derived mesenchymal stem cell engraftment after allogeneic in utero transplantation into rabbits.

    Science.gov (United States)

    Moreno, Rafael; Martínez-González, Itziar; Rosal, Marta; Nadal, Marga; Petriz, Jordi; Gratacós, Eduard; Aran, Josep M

    2012-01-20

    Prenatal transplantation of genetically engineered mesenchymal stem cells (MSCs) might benefit prevention or treatment of early-onset genetic disorders due to the cells' intrinsic regenerative potential plus the acquired advantage from therapeutic transgene expression. However, a thorough assessment of the safety, accessibility, and behavior of these MSCs in the fetal environment using appropriate animal models is required before we can advance toward a clinical application. We have recently shown that fetal rabbit liver MSCs (fl-MSCs) have superior growth rate, clonogenic capability, and in vitro adherence and differentiation abilities compared with adult rabbit bone marrow MSCs. In this follow-up study, we report safe and widespread distribution of recombinant pSF-EGFP retrovirus-transduced fl-MSCs (EGFP(+)-fl-MSCs) in neonatal rabbit tissues at 10 days after fetal allogeneic transplantation through both intrahepatic and intra-amniotic administration. Conversely, a more restricted biodistribution pattern according to the route of administration was apparent in the young rabbits intervened at 16 weeks after fetal EGFP(+)-fl-MSC transplantation. Furthermore, the presence of these cells in the recipients' tissues, tracked with the reporter provirus, was inversely related to the developmental stage of the fetuses at the time of intervention. Long-term engraftment was confirmed both by fluorescence in situ hybridization analysis on touch tissue imprints using a chromosome Y-specific BAC probe, and by immunohistochemical localization of EGFP expression. Finally, there was no evidence of immune responses against the transplanted EGFP(+)-fl-MSCs or the EGFP transgenic product in the treated young rabbits. Thus, cell transplantation approaches using genetically engineered fetal MSCs may prove particularly valuable to frontier medical treatments for congenital birth defects in perinatology.

  17. Inoculation site from a cutaneous melanoma patient treated with an allogeneic therapeutic vaccine: a case report

    Directory of Open Access Journals (Sweden)

    Mariana eAris

    2015-03-01

    Full Text Available We have developed a therapeutic vaccine consisting of a mixture of lethally-irradiated allogeneic cutaneous melanoma cell lines with BCG and GM-CSF as adjuvants. The CSF-470 vaccine is currently being assayed in a Phase II-III trial against medium-dose IFN-a2b. All vaccinated patients immunized intradermally developed large edematous erythema reactions, which then transformed into subcutaneous nodules active for several months. However, vaccine injection sites were not routinely biopsied. We describe the case of a female patient, previously classified as stage III, but who, due to the simultaneous discovery of bone metastases, only received one vaccination, was withdrawn from the study and continued her treatment elsewhere. Patient #1 developed a post-vaccination nodule which was surgically removed 7 weeks later, and allowed to analyze the reactivity and immune profiling of the inoculation site. An inflammatory reaction with zones of fibrosis, high irrigation and brisk lymphoid infiltration, primarily composed of CD8+ and CD20+ lymphocytes, was observed. There were no remaining BCG bacilli, and scarce CD4+ and Foxp3+ T cells were observed. MART-1 Ag was found throughout the vaccination site. CD11c+ Ag presenting cells were either dispersed or forming dense nests. Some CD11c+ cells proliferated; most of them contained intracellular MART-1 Ag, and some interacted with CD8+ lymphocytes. These observations suggest a potent, long-lasting local inflammatory response with recruitment of Ag-presenting cells that incorporate melanoma Ags, probably leading to Ag presentation to naïve T cells.

  18. Isolated central nervous system relapse of chronic myeloid leukemia after allogeneic hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Fuchs Mary

    2012-08-01

    Full Text Available Abstract Background This case report highlights the relevance of quantifying the BCR-ABL gene in cerebrospinal fluid of patients with suspected relapse of chronic myeloid leukemia in the central nervous system. Case presentation We report on a female patient with isolated central nervous system relapse of chronic myeloid leukemia (CML during peripheral remission after allogeneic hematopoietic stem cell transplantation. The patient showed a progressive cognitive decline as the main symptom. MRI revealed a hydrocephalus and an increase in cell count in the cerebrospinal fluid (CSF with around 50% immature blasts in the differential count. A highly elevated BCR-ABL/ ABL ratio was detected in the CSF, whilst the ratio for peripheral blood and bone marrow was not altered. On treatment of the malresorptive hydrocephalus with shunt surgery, the patient showed an initial cognitive improvement, followed by a secondary deterioration. At this time, the cranial MRI showed leukemic infiltration of lateral ventricles walls. Hence, intrathecal administration of cytarabine, methotrexate, and dexamethasone was initiated, which caused a significant decrease of cells in the CSF. Soon after, the patient demonstrated significant cognitive improvement with a good participation in daily activities. At a later time point, after the patient had lost the major molecular response of CML, therapy with dasatinib was initiated. In a further follow-up, the patient was neurologically and hematologically stable. Conclusions In patients with treated CML, the rare case of an isolated CNS blast crisis has to be taken into account if neurological symptoms evolve. The analysis of BCR-ABL in the CSF is a further option for the reliable detection of primary isolated relapse of CML in these patients.

  19. Pharmacokinetics, pharmacodynamics, and pharmacogenomics of immunosuppressants in allogeneic hematopoietic cell transplantation: Part I

    Science.gov (United States)

    McCune, Jeannine S.; Bemer, Meagan J.

    2015-01-01

    Although immunosuppressive treatments and target concentration intervention (TCI) have significantly contributed to the success of allogeneic hematopoietic cell transplant (alloHCT), there is currently no consensus on the best immunosuppressive strategies. Compared to solid organ transplant, alloHCT is unique because of the potential for bi-directional reactions (i.e., host-versus-graft and graft-versus-host). Postgraft immunosuppression typically includes a calcineurin inhibitor (cyclosporine or tacrolimus) and a short course of methotrexate after high-dose myeloablative conditioning or a calcineurin inhibitor and mycophenolate mofetil after reduced-intensity conditioning. There are evolving roles for the antithymyocyte globulins (ATG) and sirolimus as postgraft immunosuppression. A review of the pharmacokinetics and TCI of the main postgraft immunosuppressants is presented in this two-part review. All immunosuppressants are characterized by large intra- and interindividual pharmacokinetic variability and by narrow therapeutic indices. It is essential to understand immunosuppressants’ pharmacokinetic properties and how to use them for individualized treatment incorporating TCI to improve outcomes. TCI, which is mandatory for the calcineurin inhibitors and sirolimus, has become an integral part of postgraft immunosuppression. TCI is usually based on trough concentration monitoring, but other approaches include measurement of the area under the concentration-time curve (AUC) over the dosing interval or limited sampling schedules with maximum a posteriori Bayesian personalization approaches. Interpretation of pharmacodynamic results is hindered by the prevalence of studies enrolling only a small number of patients, variability in the allogeneic graft source, and variability in postgraft immunosuppression. Given the curative potential of alloHCT, the pharmacodynamics of these immunosuppressives deserves to be explored in depth. The development of sophisticated

  20. Pharmacokinetics, Pharmacodynamics and Pharmacogenomics of Immunosuppressants in Allogeneic Haematopoietic Cell Transplantation: Part I.

    Science.gov (United States)

    McCune, Jeannine S; Bemer, Meagan J

    2016-05-01

    Although immunosuppressive treatments and target concentration intervention (TCI) have significantly contributed to the success of allogeneic haematopoietic cell transplantation (alloHCT), there is currently no consensus on the best immunosuppressive strategies. Compared with solid organ transplantation, alloHCT is unique because of the potential for bidirectional reactions (i.e. host-versus-graft and graft-versus-host). Postgraft immunosuppression typically includes a calcineurin inhibitor (cyclosporine or tacrolimus) and a short course of methotrexate after high-dose myeloablative conditioning, or a calcineurin inhibitor and mycophenolate mofetil after reduced-intensity conditioning. There are evolving roles for the antithymyocyte globulins (ATGs) and sirolimus as postgraft immunosuppression. A review of the pharmacokinetics and TCI of the main postgraft immunosuppressants is presented in this two-part review. All immunosuppressants are characterized by large intra- and interindividual pharmacokinetic variability and by narrow therapeutic indices. It is essential to understand immunosuppressants' pharmacokinetic properties and how to use them for individualized treatment incorporating TCI to improve outcomes. TCI, which is mandatory for the calcineurin inhibitors and sirolimus, has become an integral part of postgraft immunosuppression. TCI is usually based on trough concentration monitoring, but other approaches include measurement of the area under the concentration-time curve (AUC) over the dosing interval or limited sampling schedules with maximum a posteriori Bayesian personalization approaches. Interpretation of pharmacodynamic results is hindered by the prevalence of studies enrolling only a small number of patients, variability in the allogeneic graft source and variability in postgraft immunosuppression. Given the curative potential of alloHCT, the pharmacodynamics of these immunosuppressants deserves to be explored in depth. Development of

  1. The evolution of allogeneic stem cell transplant for children and adolescents with acute myeloid leukemia.

    Science.gov (United States)

    Flower, Allyson; Cairo, Mitchell S

    2017-01-01

    Survival rates in subsets of pediatric patients who have acute myeloid leukemia (AML) with favorable risk features are now greater than 90%. However, outcomes for patients with high-risk (HR) features remain unacceptably poor. As novel technologies for the identification of HR biomarkers and the detection of residual disease are developed, risk stratification and the application of allogeneic hematopoietic stem cell transplant (HSCT) are evolving. HSCT has been shown to benefit subpopulations of pediatric patients with AML, including those with HR cytogenetic translocations, genetic mutations, and/or residual disease after induction. Targeted therapies have shown promise for improving outcomes, and their integration into standard therapy and HSCT regimens is a critical area of interest. Also, expansion of the donor pool has led to the successful use of alternative donor sources for those patients without a matched sibling. However, transplant-related morbidity and mortality and late effects are major limiting factors. Reduced-intensity conditioning regimens have resulted in outcomes equivalent to those achieved with myeloablative regimens among patients in complete remission. The limitation of transplant-related morbidity and mortality through reduced-intensity conditioning and supportive care, and improved survival through optimal alloreactivity in combination with targeted therapy, are steps toward advancing outcomes for pediatric patients who have AML with HR features.

  2. Effects of T-Cell Depletion on Allogeneic Hematopoietic Stem Cell Transplantation Outcomes in AML Patients

    Directory of Open Access Journals (Sweden)

    Gabriela Soriano Hobbs

    2015-03-01

    Full Text Available Graft versus host disease (GVHD remains one of the leading causes of morbidity and mortality associated with conventional allogeneic hematopoietic stem cell transplantation (HCT. The use of T-cell depletion significantly reduces this complication. Recent prospective and retrospective data suggest that, in patients with AML in first complete remission, CD34+ selected grafts afford overall and relapse-free survival comparable to those observed in recipients of conventional grafts, while significantly decreasing GVHD. In addition, CD34+ selected grafts allow older patients, and those with medical comorbidities or with only HLA-mismatched donors to successfully undergo transplantation. Prospective data are needed to further define which groups of patients with AML are most likely to benefit from CD34+ selected grafts. Here we review the history of T-cell depletion in AML, and techniques used. We then summarize the contemporary literature using CD34+ selection in recipients of matched or partially mismatched donors (7/8 or 8/8 HLA-matched, and provide a summary of the risks and benefits of using T-cell depletion.

  3. Comparison of immunological properties of bone marrow stromal cells and adipose tissue-derived stem cells before and after osteogenic differentiation in vitro

    DEFF Research Database (Denmark)

    Niemeyer, Philipp; Kornacker, Martin; Mehlhorn, Alexander

    2007-01-01

    Mesenchymal stem cells (MSCs) can be isolated from various tissues and represent an attractive cell population for tissue-engineering purposes. MSCs from bone marrow (bone marrow stromal cells [BMSCs]) are negative for immunologically relevant surface markers and inhibit proliferation of allogenic...... T cells in vitro. Therefore, BMSCs are said to be available for allogenic cell therapy. Although the immunological characteristics of BMSCs have been the subject of various investigations, those of stem cells isolated from adipose tissue (ASCs) have not been adequately described. In addition......, the influence of osteogenic differentiation in vitro on the immunological characteristics of BMSCs and ASCs is the subject of this article. Before and after osteogenic induction, the influence of BMSCs and ASCs on the proliferative behavior of resting and activated allogenic peripheral blood mononuclear cells...

  4. Induction of Tolerance to Parental Parathyroid Grafts Using Allogeneic Thymus Tissue in DiGeorge Anomaly

    OpenAIRE

    Chinn, Ivan K.; Markert, M. Louise

    2011-01-01

    DiGeorge anomaly can affect both thymic and parathyroid function. Although athymia is corrected by allogeneic thymus transplantation, treatment options for hypoparathyroidism have been unsatisfactory. Parathyroid transplantation offers the potential for definitive cure but remains challenging due to graft rejection. Some allogeneic parathyroid grafts have functioned in adult recipients in the context of immunosuppression for renal transplants. Other efforts have attempted to reduce the alloge...

  5. Chondrogenically differentiated mesenchymal stromal cell pellets stimulate endochondral bone regeneration in critical-sized bone defects

    NARCIS (Netherlands)

    J. van der Stok (Johan); M.K.E. Koolen; H. Jahr (Holger); N. Kops (Nicole); J.H. Waarsing (Jan); H.H. Weinans (Harrie); O.P. van der Jagt (Olav)

    2014-01-01

    markdownabstractAbstract: Grafting bone defects or atrophic non-unions with mesenchymal stromal cells (MSCs)-based grafts is not yet successful. MSC-based grafts typically use undifferentiated or osteogenically differentiated MSCs and regenerate bone through intramembranous ossification.

  6. Application of MultiStem® allogeneic cells for immunomodulatory therapy: clinical progress and pre-clinical challenges in prophylaxis for graft vs host disease

    Directory of Open Access Journals (Sweden)

    Bart eVaes

    2012-11-01

    Full Text Available The last decade has seen much progress in adjunctive cell therapy for immune disorders. Both corporate and institutional Phase III studies have been run using mesenchymal stromal cells (MSC for treatment of Graft vs Host Disease (GvHD, and product approval has been achieved for treatment of pediatric GvHD in Canada and New Zealand (Prochymal®; Osiris Therapeutics. This effectiveness has prompted the prophylactic use of adherent stem cells at the time of allogeneic hematopoietic stem cell transplantation (HSCT to prevent occurrence of GvHD and possibly provide stromal support for hematopoietic recovery. The MultiStem® product is an adult adherent stem cell product derived from bone marrow which has significant clinical exposure. MultiStem cells are currently in phase II clinical studies for treatment of ischemic stroke and ulcerative colitis, with Phase I studies completed in acute myocardial infarction and for GvHD prophylaxis in allogeneic HSCT, demonstrating that MultiStem administration was well tolerated while the incidence and severity of GvHD was reduced. In advancing this clinical approach, it is important to recognize that alternate models exist based on clinical manufacturing strategies. Corporate sponsors exploit the universal donor properties of adherent stem cells and manufacture at large scale, with many products obtained from one or limited donors and used across many patients. In Europe, institutional sponsors often produce allogeneic product in a patient designated context. For this approach, disposable bioreactors producing <10 products per donor in a closed system manner are very well suited. In this review, the use of adherent stem cells for GvHD prophylaxis is summarized and the suitability of disposable bioreactors for MultiStem production is presented, with an emphasis on quality control parameters, which are critical with a multiple donor approach for manufacturing.

  7. Establishment of Donor Chimerism Using Allogeneic Bone Marrow with AMP Cell Co-infusion

    Science.gov (United States)

    2016-09-01

    to Xenotransplantation; Proj 3: Tolerance of Adaptive and Innate Human Anti-Pig Immune Responses in Humanized Mice (Proj. Leader Sykes); Admin Core...for tolerance induction to tissues or organs other than kidney. Amnion-derived multipotent progenitor (AMP) cells possess a unique immune phenotype...chimerism induction by co-transplantation of Amnion-derived Multipotent Progenitor Cells (AMP cells) in humanized mice with established immune system

  8. Establishment of donor Chimerism Using Allogeneic Bone Marrow with AMP Cell Co-infusion

    Science.gov (United States)

    2017-09-01

    induction to kidney allografts in non- human primates and humans despite the transience of donor chimerism. However, evidence indicates that durable mixed... human primate, composite tissue allograft, intrabone injection 3. ACCOMPLISHMENTS 3a. Goal of this project The major goal of this project is to...develop an optimal regimen combining non- myeloablative conditioning , infusion of AMP cells and transient post-transplant immunosuppression for the

  9. DNA viral infection in patients following allogeneic transplantation of bone marrow

    OpenAIRE

    Hubáček, Petr

    2009-01-01

    Infectious complications are very common after haematopoietic stem cell transplantation (HSCT). Beside bacterial and mycotic infections, viral infections are important cause of morbidity and mortality of these patients. Among viral infections, the most common are infections caused by DNA viruses. Between January 2001 and October 2008, we have tested samples from 217 paediatric and 382 adult patients after HSCT. In total, we have tested 15 757 samples (median 31 samples for children, 20 for ad...

  10. Romidepsin Used as Monotherapy in Sequence with Allogeneic Stem Cell Transplant in a Patient with Peripheral T-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Nicholas Finn

    2014-01-01

    Full Text Available Despite advances in the field, a clear treatment algorithm for most peripheral T-cell lymphoma (PTCL subtypes remains to be defined. Generating reliable randomized data for this type of pathology remains a challenge because of the relative rarity of the disease and the heterogeneity of subtypes. Newer agents, such as the class-I selective histone deacetylase inhibitor romidepsin, have demonstrated efficacy and manageable toxicity in the relapsed and refractory setting. Whether novel agents should be used in conjunction with more conventional cytotoxic therapies or in sequence with a transplant strategy is unknown at this time. Here we report the successful use of romidepsin monotherapy as a bridge to allogeneic stem cell transplantation in a patient who had previously relapsed after several lines of conventional cytotoxic therapy for PTCL. Romidepsin provided the patient with sufficient disease control to proceed to transplantation while remaining in complete remission.

  11. Bone Markers

    Science.gov (United States)

    ... Diabetes Diarrhea Disseminated Intravascular Coagulation (DIC) Down Syndrome Ebola Virus Infection Endocrine System and Syndromes Epilepsy Excessive ... to keep bones alive and sturdy. During early childhood and in the teenage years, new bone is ...

  12. The nonopsonic allogeneic cell phagocytosis of macrophages detected by flow cytometry and two photon fluorescence microscope.

    Science.gov (United States)

    Liu, Guang-Wei; Ma, Hai-Xia; Wu, You; Zhao, Yong

    2006-11-01

    Phagocytosis, one of the apparent functions for macrophages, represents an early and crucial event in triggering host defenses against invading pathogens as well as allo- or xenogeneic rejection. Now, some methods have been used in detecting the opsonic phagocytosis of macrophages in xenogeneic settings. Efficient nonopsonic phagocytosis analysis method has not been established yet. In the present studies, allogeneic lymphocytes pre-labeled with 5-(and-6)-carboxyfluorescein diacetate succinimidyl ester (CFSE) or derived from green fluorescent protein transgeneic B6 mice (GFP-B6 mice) were co-incubated with primary murine peritoneal macrophages (PEMs) for 1-2 h or were injected into murine peritoneal cavity for 30 to 240 min. Assays by flow cytometry (FCM) and two photon laser scanning microscope (TPM) showed an efficient uptake of both allogeneic lymphocytes and xenogeneic chicken red blood cells. The continuing process of nonopsonic phagocytosis of allogeneic lymphocytes by PEMs was recorded by TPM. Furthermore, the phenotype differences of PEMs with or without phagocytosis of allogeneic cells were determined by three-color FCMs. Significantly upregulated expressions of CD11b, CD44, TLR2 and TLR4 on PEMs were observed as early as 6 h after phagocytosis of allogeneic cells. Our present data indicated that the FCM and TPM combined method is a practical approach to detect macrophage nonopsonic phagocytosis of allogeneic lymphocytes and to identify the phenotype alteration of macrophages after phagocytosis.

  13. Visceral Leishmaniasis: A Differential Diagnosis to Remember after Bone Marrow Transplantation

    Directory of Open Access Journals (Sweden)

    Margarida Dantas Brito

    2014-01-01

    Full Text Available Leishmania infection in immunocompromised hosts is reported in the literature, mostly concerning human immunodeficiency virus infected patients. It is not well characterized in the context of stem cell transplantation. We report a rare case clinical case of visceral leishmaniasis after allogeneic bone marrow transplantation. A 50-year-old Caucasian male was referred to allogeneic bone marrow transplantation with a high-risk acute lymphoblastic B leukemia in first complete remission. Allogeneic SCT was performed with peripheral blood stem cells from an unrelated Portuguese matched donor. In the following months, patient developed mild fluctuating cytopenias, mostly thrombocytopenia (between 60 and 80∗109/L. The only significant complaint was intermittent tiredness. The common causes for thrombocytopenia in this setting were excluded—no evidence of graft versus host disease, no signs of viral or bacterial infection, and no signs of relapsed disease/dysplastic changes. The bone marrow smear performed 12 months after transplantation revealed an unsuspected diagnosis: a massive bone marrow infiltration with amastigotes.

  14. Immunological effects of donor lymphocyte infusion in patients with chronic myelogenous leukemia relapsing after bone marrow transplantation

    Directory of Open Access Journals (Sweden)

    Castro F.A.

    2004-01-01

    Full Text Available Allogeneic bone marrow transplantation (alloBMT is the only curative therapy for chronic myelogenous leukemia (CML. This success is explained by the delivery of high doses of antineoplastic agents followed by the rescue of marrow function and the induction of graft-versus-leukemia reaction mediated by allogeneic lymphocytes against host tumor cells. This reaction can also be induced by donor lymphocyte infusion (DLI producing remission in most patients with CML who relapse after alloBMT. The immunological mechanisms involved in DLI therapy are poorly understood. We studied five CML patients in the chronic phase, who received DLI after relapsing from an HLA-identical BMT. Using flow cytometry we evaluated cellular activation and apoptosis, NK cytotoxicity, lymphocytes producing cytokines (IL-2, IL-4 and IFN-gamma, and unstimulated (in vivo lymphocyte proliferation. In three CML patients who achieved hematological and/or cytogenetic remission after DLI we observed an increase of the percent of activation markers on T and NK cells (CD3/DR, CD3/CD25 and CD56/DR, of lymphocytes producing IL-2 and IFN-gamma, of NK activity, and of in vivo lymphocyte proliferation. These changes were not observed consistently in two of the five patients who did not achieve complete remission with DLI. The percent of apoptotic markers (Fas, FasL and Bcl-2 on lymphocytes and CD34-positive cells did not change after DLI throughout the different study periods. Taken together, these preliminary results suggest that the therapeutic effect of DLI in the chronic phase of CML is mediated by classic cytotoxic and proliferative events involving T and NK cells but not by the Fas pathway of apoptosis.

  15. Treatment of Aneurysmal Bone Cysts with Bioactive Glass in Children.

    Science.gov (United States)

    Syvänen, J; Nietosvaara, Y; Kohonen, I; Koskimies, E; Haara, M; Korhonen, J; Pajulo, O; Helenius, I

    2017-09-01

    Aneurysmal bone cysts represent about 1% of primary bone tumors. The standard treatment is curettage, followed by local adjuvant treatments and bone grafting. The problem is the high recurrence rate. The purpose of this study was to evaluate retrospectively the use of bioactive glass as a filling material in the treatment of aneurysmatic bone cysts in children. A total of 18 consecutive children (mean 11.3 years at surgery; 10 males; 11 lower, 6 upper limb, 1 pelvis; 15 with primary surgery) with histologically proven primary aneurysmal bone cysts operated with curettage and bioactive glass filling between 2008 and 2013 were evaluated after a mean follow-up of 2.0 years (range, 0.7-5.1 years). Two (11%) patients showed evidence of aneurysmal bone cyst recurrence and both have been re-operated for recurrence. Bone remodeling was noted in all patients with remaining growth and no growth plate disturbances were recorded. Two patients needed allogeneic blood transfusion. No intraoperative or postoperative complications were recorded. We conclude that bioactive glass is a suitable filling material for children with primary aneurysmal bone cyst. Bioactive glass did not affect bone growth and no side effects were reported.

  16. Successful Aging

    Directory of Open Access Journals (Sweden)

    Taufiqurrahman Nasihun

    2015-06-01

    Full Text Available The emerging concept of successful aging is based on evidence that in healthy individual when they get aged, there are  considerable variations in physiological functions alteration. Some people exhibiting greater, but others very few or no age related alteration. The first is called poor aging and the later is called successful pattern of aging (Lambert SW, 2008. Thus, in the simple words the successful aging concept is define as an opportunity of old people to stay  active and productive condition despite they get aged chronologically. Aging itself might be defined as the progressive accumulation of changes with time associated with or responsible for the ever-increasing susceptibility to disease and death which accompanies advancing age (Harman D, 1981. The time needed to accumulate changes is attributable to aging process. The marked emerging questions are how does aging happen and where does aging start? To answer these questions and because of the complexity of aging process, there are more than 300 aging theories have been proposed to explain how and where aging occured and started respectively. There are too many to enumerate theories and classification of aging process. In summary, all of these aging theories can be grouped into three clusters: 1. Genetics program theory, this theory suggests that aging is resulted from program directed by the genes; 2. Epigenetic theory, in these theory aging is resulted from environmental random events not determined by the genes; 3. Evolutionary theory, which propose that aging is a medium for disposal mortal soma in order to avoid competition between organism and their progeny for food and space, did not try to explain how aging occur, but possibly answer why aging occur (De la Fuente. 2009. Among the three groups of aging theories, the epigenetic theory is useful to explain and try to solve the enigma of aging which is prominently caused by internal and external environmental influences

  17. Aneurysmal bone cysts

    Directory of Open Access Journals (Sweden)

    Rangachari P

    2005-01-01

    Full Text Available Back ground: Aneurysmal bone cysts have raised intra-cystic pressures which are dynamic and diagnostic in nature. Aneurysmal bone cysts could be diagnosed from other benign cystic lesions of bone by recording their intra-cystic pressures with a spinal manometer. Raised intra-cystic pressures in aneurysmal bone cysts are maintained as long as the periosteum over the cyst is intact even in those with pathological fractures. Even though its pathology is definite its aetio-pathology is not clear Method: Fourteen out of 16 radiologically benign cystic lesions of bone were subjected to intra-cystic pressure recordings with spinal manometer. Other two cysts had displaced unimpacted pathological fractures and so their intra-cystic pressures could not be recorded. All 16 cysts were subjected to histo-pathological examination to confirm their diagnosis and to find out for any pre-existing benign pathology. All the cysts were surgically treated. Results: Fourteen benign cystic lesions of bone were diagnosed as aneurysmal bone cysts preoperatively by recording raised intra-cystic pressures and confirmed by histo-pathology. In addition, histo-pathology revealed pre-existing benign pathology. All cysts were successfully treated surgically. Conclusions: Since, there is appreciable rise in intra-cystic dynamic pressures, the aneurysmal bone cyst is considered to be due to either sudden venous obstruction or arterio-venous shunt. Pre-operative intra-cystic pressure recordings help not only to diagnose aneurysmal bone cysts but also to assess the quantum of blood loss and its replacement during surgery.

  18. Osteoinductive potential of demineralized rat bone increases with increasing donor age from birth to adulthood

    DEFF Research Database (Denmark)

    Pinholt, E M; Solheim, E

    1998-01-01

    Demineralized allogenic bone implanted in the subcutis or muscle of rodents causes formation of heterotopic bone by osteoinduction. The osteoinductive response may be weaker in primates than in rodents. It was suggested that the osteoinductive response of demineralized bone for clinical use could...... be enhanced by using young donors, because studies have indicated that the osteoinductive response is reduced in demineralized bone of old versus young donors. However, these findings may not represent a gradual decline in the osteoinductive property of bone matrix throughout the life span. We evaluated...... quantitatively, by uptake of strontium 85, the osteoinductive effect of demineralized bone matrix from newborn, 8-week-old (adolescent), and 8-month-old (adult) male Wistar rats implanted in the abdominal muscles of 8-week-old male Wistar rats. The osteoinductive response increased significantly with increasing...

  19. REVERSAL OF GRAFT-VERSUS-HOST DISEASE WITH INFUSION OF AUTOLOGOUS BONE MARROW

    Science.gov (United States)

    Ricordi, Camillo; Tzakis, Anreas G.; Zeevi, Adriana; Rybka, Witold B.; Demetris, Anthony J.; Fontes, Paulo A.C.; Nalesnik, Michael A.; Trucco, Massimo; Ukah, Ferdinand O.; Ball, Edward D.; Mullen, Edward E.; Marino, Ignazio R.; Fung, John J.; Starzl, Thomas E.

    2010-01-01

    Graft-versus-host disease (GVHD) remains a major complication of bone marrow transplantation. This report describes reversal of GVHD by infusion of stored recipient bone marrow following combined liver-bone marrow allotransplantation. Graft-versus-host disease developed at the end of the first postoperative week. The skin involvement progressively spread to approximately 80% of the body surface and was not affected by modification of the immunosuppressive treatment. On the 42nd and 43rd postoperative day 1.23 × 108 and 1.6 × 108 autologous bone marrow cells per kg of recipient body weight were infused. The skin rush began to dramatically improve and resolved within 2 wk from the autologous marrow infusion. Autologous bone marrow storage previous to allogeneic bone marrow transplantation for tolerance induction could constitute a safety net in case of occurrence of GVHD. PMID:8012734

  20. Bone quality: the material and structural basis of bone strength.

    Science.gov (United States)

    Seeman, Ego

    2008-01-01

    The material composition and structural design of bone determine its strength. Structure determines loads that can be tolerated but loads also determine structure. Bone modifies its material composition and structure to accommodate loads by adaptive modeling and remodeling. Adaptation is successful during growth but not aging because accumulating insults, including a reduction in the volume of bone formed in the basic multicellular unit (BMU), increased resorption in the BMU, increased remodeling rate in midlife in women and in some men because of sex hormone deficiency, and in both sexes in old age as a consequence of secondary hyperparathyroidism and reduced periosteal bone formation, all of which compromises the material composition of bone and its structure. An understanding of the mechanisms of adaptation and failed adaptation provides rational approaches to interventions that can prevent or restore bone fragility.

  1. BMP6-Engineered MSCs Induce Vertebral Bone Repair in a Pig Model: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Gadi Pelled

    2016-01-01

    Full Text Available Osteoporotic patients, incapacitated due to vertebral compression fractures (VCF, suffer grave financial and clinical burden. Current clinical treatments focus on symptoms’ management but do not combat the issue at the source. In this pilot study, allogeneic, porcine mesenchymal stem cells, overexpressing the BMP6 gene (MSC-BMP6, were suspended in fibrin gel and implanted into a vertebral defect to investigate their effect on bone regeneration in a clinically relevant, large animal pig model. To check the effect of the BMP6-modified cells on bone regeneration, a fibrin gel only construct was used for comparison. Bone healing was evaluated in vivo at 6 and 12 weeks and ex vivo at 6 months. In vivo CT showed bone regeneration within 6 weeks of implantation in the MSC-BMP6 group while only minor bone formation was seen in the defect site of the control group. After 6 months, ex vivo analysis demonstrated enhanced bone regeneration in the BMP6-MSC group, as compared to control. This preclinical study presents an innovative, potentially minimally invasive, technique that can be used to induce bone regeneration using allogeneic gene modified MSCs and therefore revolutionize current treatment of challenging conditions, such as osteoporosis-related VCFs.

  2. Mechanisms of Guided Bone Regeneration: A Review

    Science.gov (United States)

    Liu, Jie; Kerns, David G

    2014-01-01

    Post-extraction crestal bone resorption is common and unavoidable which can lead to significant ridge dimensional changes. To regenerate enough bone for successful implant placement, Guided Bone Regeneration (GBR) is often required. GBR is a surgical procedure that uses barrier membranes with or without particulate bone grafts or/and bone substitutes. There are two approaches of GBR in implant therapy: GBR at implant placement (simultaneous approach) and GBR before implant placement to increase the alveolar ridge or improve ridge morphology (staged approach). Angiogenesis and ample blood supply play a critical role in promoting bone regeneration. PMID:24894890

  3. Animal Models of Bone Metastasis

    Science.gov (United States)

    Simmons, J. K.; Hildreth, B. E.; Supsavhad, W.; Elshafae, S. M.; Hassan, B. B.; Dirksen, W. P.; Toribio, R. E.; Rosol, T. J.

    2015-01-01

    Bone is one of the most common sites of cancer metastasis in humans and is a significant source of morbidity and mortality. Bone metastases are considered incurable and result in pain, pathologic fracture, and decreased quality of life. Animal models of skeletal metastases are essential to improve the understanding of the molecular pathways of cancer metastasis and growth in bone and to develop new therapies to inhibit and prevent bone metastases. The ideal animal model should be clinically relevant, reproducible, and representative of human disease. Currently, an ideal model does not exist; however, understanding the strengths and weaknesses of the available models will lead to proper study design and successful cancer research. This review provides an overview of the current in vivo animal models used in the study of skeletal metastases or local tumor invasion into bone and focuses on mammary and prostate cancer, lymphoma, multiple myeloma, head and neck squamous cell carcinoma, and miscellaneous tumors that metastasize to bone. PMID:26021553

  4. Exercise intensity classification in cancer patients undergoing allogeneic HCT.

    Science.gov (United States)

    Kuehl, Rea; Scharhag-Rosenberger, Friederike; Schommer, Kai; Schmidt, Martina E; Dreger, Peter; Huber, Gerhard; Bohus, Martin; Ulrich, Cornelia M; Wiskemann, Joachim

    2015-05-01

    Exercise intervention studies during and after cancer treatment show beneficial effects for various physical and psychosocial outcomes. Current exercise intensity guidelines for cancer patients are rather general and have been adapted from American College of Sports Medicine (ACSM) recommendations for healthy individuals. Intensive cancer treatment regimens such as allogeneic hematopoietic stem cell transplantation (allo-HCT) may change the cardiovascular response to acute exercise. Therefore, we evaluated the relationships between %V˙O2 reserve (%V˙O2R, reference) and %HRR, %HRmax, and %V˙O2max and compared calculated intensities with given intensities by ACSM. Measurements before and 180 d after allo-HCT from a randomized controlled trial were used. Only patients who reached maximal effort and at least two exercise stages in our maximal incremental cycling test were included. Before allo-HCT, 106 patients were included, and 180 d after treatment, 49 patients met our inclusion criteria. Individual regression lines were calculated with V˙O2R as the reference. Calculated exercise intensities for endurance training prescription were compared with ACSM values. Before allo-HCT, %HRR values of patients were significantly lower than ACSM values, and %HRmax and %V˙O2max values were significantly higher (except 90% HRmax, which was significantly lower, all P exercise intensity recommendations for endurance training may not be applicable for cancer patients during and 180 d after allo-HCT because they may not meet the targeted intensity class, with the exception of %HRR 180 d after allo-HCT.

  5. Allogenic banking of dental pulp stem cells for innovative therapeutics

    Science.gov (United States)

    Collart-Dutilleul, Pierre-Yves; Chaubron, Franck; De Vos, John; Cuisinier, Frédéric J

    2015-01-01

    Medical research in regenerative medicine and cell-based therapy has brought encouraging perspectives for the use of stem cells in clinical trials. Multiple types of stem cells, from progenitors to pluripotent stem cells, have been investigated. Among these, dental pulp stem cells (DPSCs) are mesenchymal multipotent cells coming from the dental pulp, which is the soft tissue within teeth. They represent an interesting adult stem cell source because they are recovered in large amount in dental pulps with non-invasive techniques compared to other adult stem cell sources. DPSCs can be obtained from discarded teeth, especially wisdom teeth extracted for orthodontic reasons. To shift from promising preclinical results to therapeutic applications to human, DPSCs must be prepared in clinical grade lots and transformed into advanced therapy medicinal products (ATMP). As the production of patient-specific stem cells is costly and time-consuming, allogenic biobanking of clinical grade human leukocyte antigen (HLA)-typed DPSC lines provides efficient innovative therapeutic products. DPSC biobanks represent industrial and therapeutic innovations by using discarded biological tissues (dental pulps) as a source of mesenchymal stem cells to produce and store, in good manufacturing practice (GMP) conditions, DPSC therapeutic batches. In this review, we discuss about the challenges to transfer biological samples from a donor to HLA-typed DPSC therapeutic lots, following regulations, GMP guidelines and ethical principles. We also present some clinical applications, for which there is no efficient therapeutics so far, but that DPSCs-based ATMP could potentially treat. PMID:26328017

  6. Experimental allogenic transplantation of cornea endothelial cells in cats.

    Science.gov (United States)

    Kiełbowicz, Z; Kuryszko, J; Strzadała, L

    2010-01-01

    The aim of the present study was assessing the possibility of experimental allogenic transplantation of cat cornea endothelial cells, multiplied in vitro, into the anterior chamber of the eyeball in recipient cats. The reason for undertaking the research is the need to develop a method that would help in the cornea treatment in animals with corneal opacification following cataract surgery, as well as lens dislocation, injuries and endothelium degeneration. Cats aged 10-12 months were used in the experiment. Cornea fragments consisting of the posterior limiting membrane and posterior epithelium were placed in Iscove's medium with addition of 10% foetal calf serum. Multiplied in vitro cells were injected into the anterior chamber of recipient cats. The cornea was subject to histological, histometric and SEM examination on the 3rd, 7th, 20th and 30th day after the surgery. Micromorphological examination of the cornea showed full restitution of its endothelium 30 days after transplantation. Complete regeneration of structures indispensable for normal functioning of the posterior epithelium occurred as a result of implantation. In this study the results show that implantation of the cells of posterior corneal epithelium of donor cats, multiplied into vitro and injected into the anterior chamber of recipient cats. The cornea regained its full function, the layer of the posterior epithelium was regenerated and the stroma stabilized, presenting the image of full and proper corneal translucency.

  7. Alternative donor allogeneic hematopoietic cell transplantation for hemoglobinopathies.

    Science.gov (United States)

    Alfraih, Feras; Aljurf, Mahmoud; Fitzhugh, Courtney D; Kassim, Adetola A

    2016-04-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) offers a curative therapy for patients with hemoglobinopathies, mainly severe sickle cell disease (SCD) and thalassemia (TM). However, the applicability of HSCT has been limited mainly by donor availability, with a less than 25%-30% of eligible patients having human leukocyte antigen (HLA)-matched sibling donors. Previous outcomes using alternate donor options have been markedly inferior due to increased regimen-related toxicity, transplant-related mortality, graft failure, and graft-versus-host disease (GVHD). Advances in transplant technology, including high-resolution HLA typing, improved GVHD prophylactic approaches with tolerance induction, and better supportive care over the last decade, are addressing these historical challenges, resulting in increasing donor options. Herein, we review alternate donor HSCT approaches for severe SCD and TM using unrelated donors, umbilical cord blood units, or related haploidentical donors. Though this is an emerging field, early results are promising and in selected patients, this may be the preferred option to mitigate against the age-related morbidity and early mortality associated with these disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. EXPERIENCE OF USING ALLOGENIC BIOIMPLANTS IN LARYNGEAL RESECTION

    Directory of Open Access Journals (Sweden)

    E. N. Novozhilova

    2017-01-01

    Full Text Available Introduction. Currently, a great importance is being attached to improvement of the surgical component of combination treatment of locally advanced laryngeal cancer. New technological capabilities (transoral microsurgery of the larynx and robotic surgery offer great opportunities for early cancer stages. However, in some cases capabilities of endoscopic laser intervention are limited. Therefore, open laryngeal resection is still relevant as it serves as the only type of radical organ preservation treatment for stages Т2–Т3. But major laryngeal resection is associated with a problem of tissue defect closure.The article describes data on the use of biocompatible materials, their advantages and disadvantages. The study objective is to present experience of using a Russian allogenic bioimplant for plastic reconstruction of the opening of the larynx after laryngeal resection.Materials and methods. The authors present their experience of using a Russian bioimplant produced in collaboration with the Samara Tissue Bank of the Research Institute of Experimental Medicine and Biotechnology of the Samara State Medical University. The material was tested in anterolateral laryngeal resection with simultaneous reconstruction in 5 patients with stages Т2–Т3 laryngeal cancer and in a patient with chondrosarcoma.Conclusion. The Russian biocompatible implant served as a reliable, simple, cheap, and effective variant of plastic material for reconstruction of the larynx.

  9. Treatment of CMV infection after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Maffini, Enrico; Giaccone, Luisa; Festuccia, Moreno; Brunello, Lucia; Busca, Alessandro; Bruno, Benedetto

    2016-06-01

    Despite a remarkable reduction in the past decades, cytomegalovirus (CMV) disease in allogeneic hematopoietic stem cell transplant (HSCT) recipients remains a feared complication, still associated with significant morbidity and mortality. Today, first line treatment of CMV infection/reactivation is still based on dated antiviral compounds Ganciclovir (GCV), Foscarnet (FOS) and Cidofovir (CDF) with their burdensome weight of side effects. Maribavir (MBV), Letermovir (LMV) and Brincidofovir (BDF) are three new promising anti-CMV drugs without myelosuppressive properties or renal toxic effects that are under investigation in randomized phase II and III trials. Adoptive T-cell therapy (ATCT) in CMV infection possesses a strong rationale, demonstrated by several proof of concept studies; its feasibility is currently under investigation by clinical trials. ATCT from third-party and naïve donors could meet the needs of HSCT recipients of seronegative donors and cord blood grafts. In selected patients such as recipients of T-cell depleted grafts, ATCT, based on CMV-specific host T-cells reconstitution kinetics, would be of value in the prophylactic and/or preemptive CMV treatment. Vaccine-immunotherapy has the difficult task to reduce the incidence of CMV reactivation/infection in highly immunocompromised HSCT patients. Newer notions on CMV biology may represent the base to flush out the Troll of transplantation.

  10. Prophylaxis of cytomegalovirus infection with ganciclovir in allogeneic marrow transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Yau, J.C.; Dimopoulos, M.A.; Huan, S.D.; Tarrand, J.J.; Spencer, V.; Spitzer, G.; Meneghetti, C.M.; Wallerstein, R.O.; Andersson, B.S.; LeMaistre, C.F. (Department of Hematology and Department of Laboratory Medicine, The University of Texas, M.D. Anderson Cancer Center, Houston, Texas (United States))

    1991-01-01

    Cytomegalovirus (CMV) infection is one of the most common causes of morbidity and mortality after allogeneic marrow transplantation. We studied 14 consecutive CMV-seropositive patients adding ganciclovir (2.5 mg/kg i.v. every 8 hours for 7 days prior to transplant and 6 mg/kg three times a week after neutrophils became >0.5x10{sup 9}/l and the patients were platelet transfusion-independent until d 70) to our previous prophylaxis regimen which consisted of intravenous immunoglobulin and acyclovir. The result was compared with 30 consecutive patients whom we studied with our previous regimen. The addition of ganciclovir did not cause any extra toxicities. The incidence of interstitial pneumonitis and cumulative probability of CMV excretion in the first 100 d post-transplantation was significantly reduced (p = 0.038 and p = 0.035 respectively). The result shows that addition of ganciclovir significantly decreased the incidence of CMV infection in the early post-transplantation period. (au).

  11. T cell reconstitution in allogeneic haematopoietic stem cell transplantation

    DEFF Research Database (Denmark)

    Kielsen, K; Jordan, K K; Uhlving, H H

    2015-01-01

    Infections and acute graft-versus-host disease (aGVHD) are major causes of treatment-related mortality and morbidity following allogeneic haematopoietic stem cell transplantation (HSCT). Both complications depend on reconstitution of the T-lymphocyte population based on donor T cells. Although...... it is well established that Interleukin-7 (IL-7) is a cytokine essential for de novo T cell development in the thymus and homoeostatic peripheral expansion of T cells, associations between circulating levels of IL-7 and T cell reconstitution following HSCT have not been investigated previously. We...... in patients treated with anti-thymocyte globulin (ATG) compared with those not treated with ATG (P = 0.0079). IL-7 levels at day +7 were negatively associated with T cell counts at day +30 to +60 (at day +60: CD3(+) : β = -10.6 × 10(6) cells/l, P = 0.0030; CD8(+) : β = -8.4 × 10(6) cells/l, P = 0.061; CD4...

  12. Bone morphogenetic proteins: periodontal regeneration.

    Science.gov (United States)

    Rao, Subramaniam M; Ugale, Gauri M; Warad, Shivaraj B

    2013-03-01

    Periodontitis is an infectious inflammatory disease that results in attachment loss and bone loss. Regeneration of the periodontal tissues entails de novo formation of cementum, periodontal ligament, and alveolar bone. Several different approaches are currently being explored to achieve complete, reliable, and reproducible regeneration of periodontal tissues. The therapeutic management of new bone formation is one of the key issues in successful periodontal regeneration. Bone morphogenetic proteins form a unique group of proteins within the transforming growth factor superfamily of genes and have a vital role in the regulation in the bone induction and maintenance. The activity of bone morphogenetic proteins was first identified in the 1960s, but the proteins responsible for bone induction were unknown until the purification and cloning of human bone morphogenetic proteins in the 1980s, because of their osteoinductive potential. Bone morphogenetic proteins have gained a lot of interest as therapeutic agents for treating periodontal defects. A systematic search for data related to the use of bone morphogenetic proteins for the regeneration of periodontal defects was performed to recognize studies on animals and human (PUBMED, MEDLINE, COCHRANE, and Google search). All the studies included showed noticeable regeneration of periodontal tissues with the use of BMP.

  13. Minor Antigen Disparities Impede Induction of Long Lasting Chimerism and Tolerance through Bone Marrow Transplantation with Costimulation Blockade

    Directory of Open Access Journals (Sweden)

    Sinda Bigenzahn

    2016-01-01

    Full Text Available Mixed chimerism and tolerance can be successfully induced in rodents through allogeneic bone marrow transplantation (BMT with costimulation blockade (CB, but varying success rates have been reported with distinct models and protocols. We therefore investigated the impact of minor antigen disparities on the induction of mixed chimerism and tolerance. C57BL/6 (H2b mice received nonmyeloablative total body irradiation (3 Gy, costimulation blockade (anti-CD40L mAb and CTLA4Ig, and 2×107 bone marrow cells (BMC from either of three donor strains: Balb/c (H2d (MHC plus multiple minor histocompatibility antigen (mHAg mismatched, B10.D2 (H2d or B10.A (H2a (both MHC mismatched, but mHAg matched. Macrochimerism was followed over time by flow cytometry and tolerance was tested by skin grafting. 20 of 21 recipients of B10.D2 BMC but only 13 of 18 of Balb/c BMC and 13 of 20 of B10.A BMC developed stable long-term multilineage chimerism (p<0.05 for each donor strain versus B10.D2. Significantly superior donor skin graft survival was observed in successfully established long-term chimeras after mHAg matched BMT compared to mHAg mismatched BMT (p<0.05. Both minor and major antigen disparities pose a substantial barrier for the induction of chimerism while the maintenance of tolerance after nonmyeloablative BMT and costimulation blockade is negatively influenced by minor antigen disparities.

  14. Peripheral blood stem cell collection for allogeneic hematopoietic stem cell transplantation: Practical implications after 200 consequent transplants.

    Science.gov (United States)

    Goren Sahin, Deniz; Arat, Mutlu

    2017-12-01

    Proper stem cell mobilization is one of the most important steps in hematopoietic stem cell transplantation (HSCT). The aim of this paper is to share our 6 years' experience and provide practical clinical approaches particularly for stem cell mobilization and collection within the series of more than 200 successive allogeneic HSCT at our transplant center. Two hundred and seven consecutive patients who underwent allogeneic peripheral blood stem cell transplantation were included in this study. Age, sex, weight, complete blood counts, CD34+ cell counts, total collected amount of CD34+ cells, CD34+ cells per 10l processed, mobilization failure and adverse events were reviewed. Median age was 40.2±12.9 (21-68) years and 46.4±13.4 (17-67) years for donors and patients, respectively. The number of donors who had undergone adequate CD34+ cell harvesting and completed the procedure on the fourth day was 67 (32.8% of all patients). Only 12 patients required cell apheresis both on day 5 and 6. Apheresis was completed on day 4 and/or day 5 in 94.2% of all our donors. There was no significant association between CD34+ stem cell volume and age, gender and weight values of donors. Mobilization failure was not seen in our series. G-CSF is highly effective in 1/3 of the donors on the 4th day in order to collect enough number of stem cells. We propose that peripheral stem cell collection might start on day 4th of G-CSF treatment for avoiding G-CSF related side effects and complications. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Syringomyelia in mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome): imaging findings following bone marrow transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Hite, S.H. [Department of Radiology, Box 292, University of Minnesota Hospital and Clinic, 420 Delaware Street SE, Minneapolis, MN 55455 (United States); Krivit, W. [Department of Pediatrics and Institute for Human Genetics, University of Minnesota Hospital and Clinic, Minneapolis, MN (United States); Haines, S.J. [Department of Neurological Surgery, University of Minnesota Hospital and Clinic, Minneapolis, MN (United States); Whitley, C.B. [Department of Pediatrics and Institute for Human Genetics, University of Minnesota Hospital and Clinic, Minneapolis, MN (United States)

    1997-09-01

    We present the imaging findings in a patient with mucopolysaccharidosis (MPS) type VI (Maroteaux-Lamy syndrome) who developed holocord syringomyelia. This represents the only reported case of syrinx formation in a child with MPS VI. Clinical, neurologic and spinal magnetic resonance imaging findings are presented. The patient has maintained a stable clinical and neurologic course over the period following allogeneic bone marrow transplant. (orig.). With 3 figs.

  16. The Fresh Frozen Bone Allograft (FFBA) to reconstruc the atrophic maxilla: evaluation of the clinical and histological viability at six and nine months in the maxillary sinus

    OpenAIRE

    Bassi, Ana Paula Farnezi; Vieira, Rogeria A; Matsumoto, Marisa Akemi; Stecklberg, Iris Monica; Ferreira,Gabriel Ramalho; FAVERANI,Leonardo Perez

    2013-01-01

    This work aimed to analyze clinically and histologically the allogen bone graft behavior at 6 and 9 months. A leukoderm, female, 55 years old patient sought dental care for oral rehabilitation with dental implants and implant supported fixed prosthesis in the maxilla. Bilateral sinus lifting procedure were performed in a same patient, the analysis were made after 6 and 9 months, respectively. At 6 months, there was lack of a better bone remodeling in the region, associated to the presence of ...

  17. Tissue-engineered polymer-based periosteal bone grafts for maxillary sinus augmentation: five-year clinical results.

    Science.gov (United States)

    Trautvetter, Wolfram; Kaps, Christian; Schmelzeisen, Rainer; Sauerbier, Sebastian; Sittinger, Michael

    2011-11-01

    Augmentation of the maxillary sinus with allogenic or alloplastic materials, as well as autologous bone grafts, has inherent disadvantages. Therefore, the aim of our study was to evaluate the long-term clinical repair effect of autologous periosteal bone grafts on atrophic maxillary bone. In the present retrospective cohort study, augmentation of the edentulous atrophic posterior maxilla was performed using autologous tissue-engineered periosteal bone grafts based on bioresorbable polymer scaffolds and, in a 1-step procedure, simultaneous insertion of dental implants. The clinical evaluation of 10 patients was performed by radiologic assessment of bone formation, with a follow-up of 5 years. Bone formation was further documented by measuring the bone height and by histologic examination. Excellent clinical and radiologic results were achieved as early as 4 months after transplantation of the periosteal bone grafts. The bone height remained significantly (P bone (median 6.9 mm) during the 5-year observation period. Histologically, the bone biopsy specimens of 2 patients obtained after 6 months showed trabecular bone with osteocytes and active osteoblasts. No signs of bone resorption, formation of connective tissue, or necrosis were seen. Our results suggest that the transplantation of autologous periosteal bone grafts and implantation of dental implants in a 1-step procedure is a reliable procedure that leads to bone formation in the edentulous posterior maxilla, remaining stable in the long term for a period of at least 5 years. Copyright © 2011 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  18. Accelerated bone ingrowth by local delivery of Zinc from bioactive ...

    African Journals Online (AJOL)

    Background: Synthetic bone graft substitutes such as bioactive glass (BG) material are developed in order to achieve successful bone regeneration. Zn plays an important role in the proper bone growth, development, and maintenance of healthy bones. Aims: This study aims to evaluate in vivo the performance therapy of ...

  19. THE ROLE OF AUTOLOGOUS AND ALLOGENEIC STEM CELL TRANSPLANTATION IN FOLLICULAR LYMPHOMA IN THE NEW DRUGS ERA.

    Directory of Open Access Journals (Sweden)

    Francesco Maura

    2016-09-01

    Full Text Available Follicular lymphoma (FL is the second most common histotype of non-Hodgkin’s lymphoma and it is generally characterized by a heterogeneous clinical course. Despite recent therapeutic and diagnostic improvements, a significant fraction of FL patients still relapsed. In younger and/or fit FL relapsed patients bone marrow transplant (BMT has represented the main salvage therapy for many years. Thanks to the ability of high dose chemotherapy to overcome the lymphoma resistance and refractoriness, autologous stem cell transplantation (ASCT is able to achieve a high complete remission rate (CR and favourable outcome in terms of progression free survival (PFS and overall survival (OS. Allogeneic stem cell transplantation (alloSCT combines the high dose chemotherapy effect together with the immune reaction of the donor immune system against lymphoma, the so called ‘graft versus lymphoma’ (GVL effect. Considering the generally higher transplant related mortality (TRM, alloSCT is mostly indicated for FL relapsed after ASCT. During the last years there has been a great spread of novel effective and feasible drugs Although these and future novel drugs will probably change our current approach to FL, the OS post-BMT (ASCT and alloSCT has never been reproduced by any novel combination. In this scenario, it is important to correctly evaluate the disease status, the relapse risk and the comorbidity profile of the relapsed FL patients in order to provide the best salvage therapy and eventually transplant consolidation.

  20. Radiation sterilized bone response to dynamic loading.

    Science.gov (United States)

    Mardas, Marcin; Kubisz, Leszek; Biskupski, Piotr; Mielcarek, Sławomir; Stelmach-Mardas, Marta; Kałuska, Iwona

    2012-08-01

    Allogeneic bone grafts are used on a large scale in surgeries. To avoid the risk of infectious diseases, allografts should be radiation-sterilized. So far, no international consensus has been achieved regarding the optimal radiation dose. Many authors suggest that bone sterilization deteriorates bone mechanical properties. However, no data on the influence of ionizing radiation on bone dynamic mechanical properties are available. Bovine femurs from 2-year old animal were machine cut and irradiated with the doses 10, 15, 25, 35, 45 and 50 kGy. Dynamic mechanical analysis was performed at 1-10 Hz at the temperature range of 0-350 °C in 3-point bending configuration. No statistically significant differences in storage modulus were observed. However, there were significant decreased values of loss modulus between the samples irradiated with doses of 10 (↓14.3%), 15, 45 and 50 kGy (↓33.2%) and controls. It was stated that increased irradiation dose decreases the temperature where collagen denaturation process starts and increases the temperature where the collagen denaturation process finishes. It was shown that activation energy of denaturation process is significantly higher for the samples irradiated with the dose of 50 kGy (615 kJ/mol) in comparison with control samples and irradiation with other doses (100-135 kJ/mol). Copyright © 2012 Elsevier B.V. All rights reserved.

  1. Clinical trial and in-vitro study comparing the efficacy of treating bony lesions with allografts versus synthetic or highly-processed xenogeneic bone grafts

    DEFF Research Database (Denmark)

    Kubosch, Eva Johanna; Bernstein, Anke; Wolf, Laura

    2016-01-01

    BACKGROUND: Our study aim was to compare allogeneic cancellous bone (ACB) and synthetic or highly-processed xenogeneic bone substitutes (SBS) in the treatment of skeletal defects in orthopedic surgery. METHODS: 232 patients treated for bony lesions with ACB (n = 116) or SBS (n = 116) within a 10....... Histological examination revealed similar bone structures, whereas cell remnants were apparent only in the allografts. Both materials were biocompatible in-vitro, and seeded with human osteoblasts. The cells remained vital over the 3-week culture period and produced microscopically typical bone matrix. We...

  2. Guided bone regeneration (GBR) using cortical bone pins in combination with leukocyte- and platelet-rich fibrin (L-PRF).

    Science.gov (United States)

    Toffler, Michael

    2014-03-01

    Two of the fundamental requisites for guided bone regeneration (GBR) are space maintenance and primary soft-tissue closure. Allogeneic cortical bone pins measuring 2 mm in diameter in customized lengths can protect surrounding graft materials, support bioresorbable membrane barriers, and resist wound compression from the overlying soft tissues. In addition, a second-generation platelet concentrate, leukocyte- and platelet-rich fibrin (L-PRF), may be incorporated into the augmentation procedure to provide multiple growth factors, accelerate wound healing, and aid in the maintenance of primary closure over the grafted materials. Highlighting two case reports, this article features a GBR technique that uses bone pins in combination with L-PRF membranes to provide both horizontal and vertical ridge augmentation at severely compromised implant sites.

  3. Long-term outcomes among older patients following nonmyeloablative conditioning and allogeneic hematopoietic cell transplantation for advanced hematologic malignancies

    DEFF Research Database (Denmark)

    Sorror, Mohamed L; Sandmaier, Brenda M; Storer, Barry E

    2011-01-01

    A minimally toxic nonmyeloablative regimen was developed for allogeneic hematopoietic cell transplantation (HCT) to treat patients with advanced hematologic malignancies who are older or have comorbid conditions.......A minimally toxic nonmyeloablative regimen was developed for allogeneic hematopoietic cell transplantation (HCT) to treat patients with advanced hematologic malignancies who are older or have comorbid conditions....

  4. Effect of skin fibroblast-derived allogeneic feeder cells on porcine ES-like cell establishment.

    Science.gov (United States)

    Panasophonkul, Sasithorn; Tharasanit, Theerawat; Techakumphu, Mongkol

    2012-10-01

    In the present study, the effect of two types of allogeneic-derived feeder cells [porcine ear and tail skin fibroblasts (PESF, PTSF)] and three types of xenogeneic-derived feeder cells [human foreskin fibroblasts (HFK), mouse embryonic fibroblasts (MEF) and immortalized mouse embryonic fibroblasts (STO)] on the isolation and cultivation of putative porcine embryonic stem cells (pESCs) was evaluated. In vivo derived zona pellucida (ZP)-free blastocysts were cultured on different mitotically inactivated feeder layers. The rates of ICM outgrowth and primary colony formation were observed, and further passage onto new feeders was performed. The characteristics of pESCs, including alkaline phosphatase (AP) activity, and pluripotent-related markers (OCT3/4, NANOG, SSEA-4) and genes were examined. Attached blastocysts cultured on HFK and STO feeders showed a higher percentage of ICM outgrowths than those cultured on PESF (76.7, 72.9 and 38.9%, respectively; P<0.05). The rates of primary ES-like colony formation and the number of putative ESC lines were significantly decreased when ICM outgrowths were cultured on PESF, compared with those cultured on HFK (30.6 vs. 76.7%, respectively; P<0.05). Only ES-like colonies from one (25%) and three (50%) cell lines developed on PTSF and STO feeders, respectively, were further maintained in an undifferentiated morphology associated with the presence of all ES characteristics; however, these characteristics disappeared when colonies were continued to the 8th and 6th passages, respectively. The present study indicated that feeder cell types affect the success of pESC establishment and maintenance of their pluripotency.

  5. Early Clostridium difficile infection during allogeneic hematopoietic stem cell transplantation.

    Directory of Open Access Journals (Sweden)

    Melissa A Kinnebrew

    Full Text Available Clostridium difficile infection (CDI is frequently diagnosed in recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT. We characterized early-transplant CDI and its associations, and analyzed serially-collected feces to determine intestinal carriage of toxigenic C. difficile. Fecal specimens were collected longitudinally from 94 patients during allo-HSCT hospitalization, from the start of pre-transplant conditioning until up to 35 days after stem cell infusion. Presence of C. difficile 16S rRNA and tcdB genes was determined. Clinical variables and specimen data were analyzed for association with development of CDI. Historical data from an additional 1144 allo-HSCT patients was also used. Fecal specimens from 37 patients (39% were found to harbor C. difficile. Early-transplant CDI was diagnosed in 16 of 94 (17% patients undergoing allo-HSCT; cases were generally mild and resembled non-CDI diarrhea associated with transplant conditioning. CDI was associated with preceding colonization with tcdB-positive C. difficile and conditioning regimen intensity. We found no associations between early-transplant CDI and graft-versus-host disease or CDI later in transplant. CDI occurs with high frequency during the early phase of allo-HSCT, where recipients are pre-colonized with toxigenic C. difficile. During this time, CDI incidence peaks during pre-transplant conditioning, and is correlated to intensity of the treatment. In this unique setting, high rates of CDI may be explained by prior colonization and chemotherapy; however, cases were generally mild and resembled non-infectious diarrhea due to conditioning, raising concerns of misdiagnosis. Further study of this unique population with more discriminating CDI diagnostic tests are warranted.

  6. Allogenic sedimentary components of Bear Lake, Utah and Idaho

    Science.gov (United States)

    Rosenbaum, J.G.; Dean, W.E.; Reynolds, R.L.; Reheis, M.C.

    2009-01-01

    Bear Lake is a long-lived lake filling a tectonic depression between the Bear River Range to the west and the Bear River Plateau to the east, and straddling the border between Utah and Idaho. Mineralogy, elemental geochemistry, and magnetic properties provide information about variations in provenance of allogenic lithic material in last-glacial-age, quartz-rich sediment in Bear Lake. Grain-size data from the siliciclastic fraction of late-glacial to Holocene carbonate-rich sediments provide information about variations in lake level. For the quartz-rich lower unit, which was deposited while the Bear River fl owed into and out of the lake, four source areas are recognized on the basis of modern fluvial samples with contrasting properties that reflect differences in bedrock geology and in magnetite content from dust. One of these areas is underlain by hematite-rich Uinta Mountain Group rocks in the headwaters of the Bear River. Although Uinta Mountain Group rocks make up a small fraction of the catchment, hematite-rich material from this area is an important component of the lower unit. This material is interpreted to be glacial fl our. Variations in the input of glacial flour are interpreted as having caused quasi-cyclical variations in mineralogical and elemental concentrations, and in magnetic properties within the lower unit. The carbonate-rich younger unit was deposited under conditions similar to those of the modern lake, with the Bear River largely bypassing the lake. For two cores taken in more than 30 m of water, median grain sizes in this unit range from ???6 ??m to more than 30 ??m, with the coarsest grain sizes associated with beach or shallow-water deposits. Similar grain-size variations are observed as a function of water depth in the modern lake and provide the basis for interpreting the core grain-size data in terms of lake level. Copyright ?? 2009 The Geological Society of America.

  7. Autologous cell therapy as a new approach to treatment of radiation-induced bone marrow aplasia: preliminary study in a baboon model

    Energy Technology Data Exchange (ETDEWEB)

    Herodin, F.; Drouet, M. [Radiohematology Unit, Centre de Recherches du Service de Sante des Armees, La Tronche CEDEX (France)

    2002-07-01

    The sparing of viable hematopoietic stem and progenitor cells located in underexposed bone marrow territories associated with the relative radioresistance of certain stem cell populations is the rationale for autologous cell therapy consisting of ex vivo expansion of residual cells after collection postirradiation. The feasibility of this treatment mainly depends on time constraints and hematopoietic cell threshold. We showed in this study that in the absence of early-acting mobilizing agent administration, subliminar amounts of CD34{sup +} cells can be collected (1 x 10{sup 6} CD34{sup +} cells/100 mL bone marrow or for 1 L apheresis) from 6-Gy {gamma} globally irradiated baboons. Residual CD34{sup +} cells were successfully expanded in serum-free medium in the presence of antiapoptotic cytokine combination (stem cell factor + FLT-3 ligand + thrombopoietin + interleukin 3, 50 ng/mL each, i.e., 4F): K{sub CD34{sup +}} = x2.8 and x13.7 (n=2). Moreover, we demonstrated the short-term neutrophil engraftment potential of a low-size mixed expanded graft (1.5 x 10{sup 6} final CD34{sup +}cells/kg) issued from the coculture of unirradiated (20%) and 2.5-Gy in vitro irradiated (80%) CD34{sup +} cells on an allogeneic stromal cell layer in the presence of 4F. Further preclinical research needs to be performed to clearly establish this therapeutic approach that could be optimized by the early administration of antiapoptotic cytokines. (author)

  8. A Prospective, Randomized, Masked and Placebo-Controlled Efficacy Study of Intraarticular Allogeneic Adipose Stem Cells for the Treatment of Osteoarthritis in Dogs

    Directory of Open Access Journals (Sweden)

    Robert J Harman

    2016-09-01

    Full Text Available Osteoarthritis (OA is a degenerative joint disease with a high prevalence in dogs. Mesenchymal stem cells have been used to treat humans, dogs, and horses with OA. This report describes a prospective, randomized, blinded, and placebo-controlled clinical efficacy study of intraarticular allogeneic adipose stem cells for the treatment of dogs with osteoarthritis. Health assessments and measurements of pain and activity impairment were performed at baseline and at selected time points through day 60. The primary outcome variable was the owner Client-Specific Outcome Measurement (CSOM and secondary measures included veterinary pain on manipulation, veterinary global score, and owner global score. The dogs were treated with either a saline placebo or a single dose of allogeneic adipose-derived mesenchymal stem cells in either one or two joints. Seventy-four dogs were statistically analyzed for efficacy outcomes. Success in the primary outcome variable, CSOM, was statistically improved in the treated dogs compared to the placebo dogs (79.2% versus 55.4%, p=0.029. The veterinary pain on manipulation score (92.8% versus 50.2%, p=0.017 and the veterinary global score (86.9% versus 30.8%, p= 0.009 were both statistically improved in treated dogs compared to placebo. There was no detected significant difference between treated and placebo dogs in the incidence of adverse events or negative health findings. Allogeneic adipose-derived stem cell treatment was shown to be efficacious compared to placebo. This large study of dogs also provides valuable animal clinical safety and efficacy outcome data to our colleagues developing human stem cell therapy.

  9. Allogeneic human dermal fibroblasts are viable in peripheral blood mononuclear co-culture

    Directory of Open Access Journals (Sweden)

    Restu Syamsul Hadi

    2014-08-01

    Full Text Available Background Transplanted allogeneic dermal fibroblasts retain stem cell subpopulations, and are easily isolated, expanded and stored using standard techniques. Their potential for regenerative therapy of chronic wounds should be evaluated. The aim of this study was to determine allogeneic fibroblast viability in the presence of peripheral blood mononuclear cells (PBMC. Methods In this experimental study, fibroblasts were isolated from foreskin explants, expanded in the presence of serum, and stored using slow-freezing. We used one intervention group of allogeneic fibroblasts co-cultured with PBMC and 2 control groups of separate fibroblast and PBMC cultures.Fibroblasts were characterized by their collagen secretion and octamer-binding transcription factor 4 (OCT4 expression. Viability was evaluated using water soluble tetrazolium-1 (WST-1 proliferation assay. Absorbances were measured at 450 nm. Data analysis was performed by student’s paired t-test. Results Dermal fibroblasts were shown to secrete collagen, express OCT4, be recoverable after cryopreservation, and become attached to the culture dish in a co-culture with PBMC. Co-cultured and control fibroblasts had no significantly different cell viabilities (p>0.05. Calculated viable cell numbers increased 1.8 and 5.1-fold, respectively, at days 2 and 4 in vitro. Both groups showed comparable doubling times at days 2 and 4 in vitro. PBMC did not interfere with allogeneic fibroblast viability and proliferative capacity Conclusions Allogeneic fibroblasts remain viable and proliferate in the presence of host PBMC. Future research should evaluate allogeneic human dermal fibroblast competency in clinical settings. Dermal fibroblasts are a potential source for cell therapy in chronic wound management.

  10. Allogeneic human dermal fibroblasts are viable in peripheral blood mononuclear co-culture

    Directory of Open Access Journals (Sweden)

    Restu Syamsul Hadi

    2015-12-01

    Full Text Available BACKGROUND Transplanted allogeneic dermal fibroblasts retain stem cell subpopulations, and are easily isolated, expanded and stored using standard techniques. Their potential for regenerative therapy of chronic wounds should be evaluated. The aim of this study was to determine allogeneic fibroblast viability in the presence of peripheral blood mononuclear cells (PBMC. METHODS In this experimental study, fibroblasts were isolated from foreskin explants, expanded in the presence of serum, and stored using slow-freezing. We used one intervention group of allogeneic fibroblasts co-cultured with PBMC and 2 control groups of separate fibroblast and PBMC cultures.Fibroblasts were characterized by their collagen secretion and octamer-binding transcription factor 4 (OCT4 expression. Viability was evaluated using water soluble tetrazolium-1 (WST-1 proliferation assay. Absorbances were measured at 450 nm. Data analysis was performed by student’s paired t-test. RESULTS Dermal fibroblasts were shown to secrete collagen, express OCT4, be recoverable after cryopreservation, and become attached to the culture dish in a co-culture with PBMC. Co-cultured and control fibroblasts had no significantly different cell viabilities (p>0.05. Calculated viable cell numbers increased 1.8 and 5.1- fold, respectively, at days 2 and 4 in vitro. Both groups showed comparable doubling times at days 2 and 4 in vitro. PBMC did not interfere with allogeneic fibroblast viability and proliferative capacity CONCLUSIONS Allogeneic fibroblasts remain viable and proliferate in the presence of host PBMC. Future research should evaluate allogeneic human dermal fibroblast competency in clinical settings. Dermal fibroblasts are a potential source for cell therapy in chronic wound management.

  11. [Clinical risks analysis of EBV infection in patients with allogeneic hematopoietic stem cell transplantation].

    Science.gov (United States)

    Bao, Xiebing; Zhu, Qian; Qiu, Huiying; Chen, Feng; Xue, Shengli; Ma, Xiao; Sun, Aining; Wu, Depei

    2016-02-01

    To analyze the prevalence of Epstein Barr Virus (EBV) infection in patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT). The occurrence of EBV viremia, EBV disease and post-transplant lymphoproliferative disease (PTLD) were retrospectively analyzed in 736 patients received allo-HSCT in single-center from 1st January 2012 through July 31th, 2014. Of 736 patients (302 male and 434 females) with a median age of 31 (2 to 62) years old, EBV infection occurred in 181 patients, the total incidence of EBV infection was 27.6%, with a median time of 57 (16 to 829) days. The cumulative incidences of probable EBV disease and PTLD were 7.2% (13/181) and 2.8% (5/181). Viral load higher than 1.0×10(4) copies/ml occurs in 130 patients, of which 67 patients received rituximab as pre-empty prophylaxis and significantly reduced the incidences of probable EBV disease and PTLD (6.0% vs 22.2%, P=0.009). The mortality was 27.6% in all patients with EBV infection: 24.5% in EBV viremia, 53.8% in probable EBV disease, and 60.6% in PTLD. By univariate and multivariate analysis, the use of anti-thymocyte globulin (ATG), HLA-mismatch HSCT, cGVHD and CMV reactivation were independent risk factors for EBV infection. The time of first EBV reactivation was closely related with cGVHD(OR=0.620, 95%CI 0.453-0.849, P=0.003) and bone marrow or cord blood (OR=1.156, 95%CI 1.022-2.250, P=0.039) as source of stem cells for transplantation. EBV reactivation is a common complication in patients with allo-HSCT, especially high mortality in PTLD and probable EBV disease. The use of ATG, HLA-mismatch HSCT, cGVHD and CMV reactivation were independent risk factors for EBV infection. The usage of rituximab as pre-empty prophylaxis may reduce the incidences of probable EBV disease and PTLD.

  12. Prospective, comprehensive, and effective viral monitoring in children undergoing allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Schönberger, S; Meisel, R; Adams, O; Pufal, Y; Laws, H J; Enczmann, J; Dilloo, D

    2010-10-01

    Major advances in the monitoring and treatment of viral infections after hematopoietic stem cell transplantation (HSCT) have been achieved over the last decade. The appropriate extent of viral monitoring and antiviral therapy remains controversial, and reports in pediatric patients receiving allogeneic unmanipulated hematopoietic stem cells (HSCs) are sparse. A total of 40 pediatric patients who underwent HSCT with either peripheral blood stem cells (PBSCs, n = 30) or bone marrow (BM; n = 10) were prospectively monitored every week for viral DNAemia (VDNA) by simultaneous detection of cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus 6 (HHV6), human adenovirus (ADV), and polyoma BK virus (BKV) using real-time TaqMan polymerase chain reaction (PCR). All patients received prophylactic acyclovir and preemptive ganciclovir (GCV) when 500 copies/microg DNA (EBV/HHV6) or >1 copy/microg DNA (CMV) were detected on 2 consecutive measurements. VDNA occurred in 25 of 40 recipients (CMV, 11/40 patients [28%]; EBV, 19/40 [48%]; HHV6, 2/40 [5%]; ADV/BKV, 1/40) and was found exclusively after neutrophil engraftment and in most cases up to day +100. Recurrent VDNA (P = .028) and (readily treatable) viral disease (P = .003) were observed predominantly in patients suffering from nonmalignant diseases, a cohort characterized by delayed lymphocyte engraftment. VDNA occurred more frequently in HLA-mismatched HSCT and in the 24 of 40 patients receiving antithymocyte globulin (ATG). The incidence of EBV, but not that of CMV, was increased in the ATG group. Yet, in these patients, viral loads of both EBV and CMV were higher, but with prompt initiation of preemptive GCV, no posttransplantation lymphoproliferative disorder or other life-threatening morbidities occurred. HHV6 was typically detected at low viral loads (stem cell source, but not severe acute graft-versus-host disease were identified as independent risk factors for VDNA. This comprehensive viral monitoring

  13. Allogeneic hematopoietic stem-cell transplantation for acute myeloid leukemia in remission

    DEFF Research Database (Denmark)

    Nagler, Arnon; Rocha, Vanderson; Labopin, Myriam

    2013-01-01

    Cyclophosphamide (Cy) combined with total-body irradiation (TBI) or with busulfan (Bu) are currently the most common myeloablative regimens used in allogeneic stem-cell transplantation (alloSCT) in adults with acute myelogenous leukemia (AML). Intravenous (IV) Bu has more predictable bioavailabil......Cyclophosphamide (Cy) combined with total-body irradiation (TBI) or with busulfan (Bu) are currently the most common myeloablative regimens used in allogeneic stem-cell transplantation (alloSCT) in adults with acute myelogenous leukemia (AML). Intravenous (IV) Bu has more predictable...

  14. I-131-Metaiodobenzylguanidine therapy with allogeneic cord blood stem cell transplantation for recurrent neuroblastoma

    Directory of Open Access Journals (Sweden)

    Sato Yuya

    2012-10-01

    Full Text Available Abstract Iodine-131-metaiodiobenzylguanidine (131I-MIBG therapy combined with allogeneic cord blood stem cell transplantation (SCT was used to treat a 4-year-old girl with recurrent neuroblastoma. The patient experienced relapse 2 years after receiving first-line therapies, which included chemotherapy, surgical resection, irradiation, and autologous peripheral SCT. Although 131I-MIBG treatment did not achieve complete remission, the size of the tumor was reduced after treatment. Based on our findings, we suggest that 131I-MIBG treatment with myeloablative allogeneic SCT should be considered as first-line therapy for high-risk neuroblastoma patients when possible.

  15. Allogeneic stem cell transplantation for patients harboring T315I BCR-ABL mutated leukemias

    DEFF Research Database (Denmark)

    Nicolini, Franck Emmanuel; Basak, Grzegorz W; Soverini, Simona

    2011-01-01

    T315I(+) Philadelphia chromosome-positive leukemias are inherently resistant to all licensed tyrosine kinase inhibitors, and therapeutic options remain limited. We report the outcome of allogeneic stem cell transplantation in 64 patients with documented BCR-ABL(T315I) mutations. Median follow......) as unfavorable factors. We conclude that allogeneic stem cell transplantation represents a valuable therapeutic tool for eligible patients with BCR-ABL(T315I) mutation, a tool that may or may not be replaced by third-generation tyrosine kinase inhibitors....

  16. Biomaterials for Bone Regenerative Engineering.

    Science.gov (United States)

    Yu, Xiaohua; Tang, Xiaoyan; Gohil, Shalini V; Laurencin, Cato T

    2015-06-24

    Strategies for bone tissue regeneration have been continuously evolving for the last 25 years since the introduction of the "tissue engineering" concept. The convergence of the life, physical, and engineering sciences has brought in several advanced technologies available to tissue engineers and scientists. This resulted in the creation of a new multidisciplinary field termed as "regenerative engineering". In this article, the role of biomaterials in bone regenerative engineering is systematically reviewed to elucidate the new design criteria for the next generation of biomaterials for bone regenerative engineering. The exemplary design of biomaterials harnessing various materials characteristics towards successful bone defect repair and regeneration is highlighted. Particular attention is given to the attempts of incorporating advanced materials science, stem cell technologies, and developmental biology into biomaterials design to engineer and develop the next generation bone grafts. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Anti-thymocyte globulin as graft-versus-host disease prevention in the setting of allogeneic peripheral blood stem cell transplantation: a review from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

    Science.gov (United States)

    Baron, Frédéric; Mohty, Mohamad; Blaise, Didier; Socié, Gérard; Labopin, Myriam; Esteve, Jordi; Ciceri, Fabio; Giebel, Sebastian; Gorin, Norbert Claude; Savani, Bipin N; Schmid, Christoph; Nagler, Arnon

    2017-02-01

    Allogeneic hematopoietic stem cell transplantation is increasingly used as treatment for patients with life-threatening blood diseases. Its curative potential is largely based on immune-mediated graft-versus-leukemia effects caused by donor T cells contained in the graft. Unfortunately, donor T cells are also the cause of graft-versus-host disease. The vast majority of human leukocyte antigen-matched allogeneic hematopoietic stem cell transplants are nowadays carried out with peripheral blood stem cells as the stem cell source. In comparison with bone marrows, peripheral blood stem cells contain more hematopoietic stem/progenitor cells but also one log more T cells. Consequently, the use of peripheral blood stem cells instead of bone marrow has been associated with faster hematologic recovery and a lower risk of relapse in patients with advanced disease, but also with a higher incidence of chronic graft-versus-host disease. These observations have been the basis for several studies aimed at assessing the impact of immunoregulation with anti-thymocyte globulin on transplantation outcomes in patients given human leukocyte antigen-matched peripheral blood stem cells from related or unrelated donors. After a brief introduction on anti-thymocyte globulin, this article reviews recent studies assessing the impact of anti-thymocyte globulin on transplantation outcomes in patients given peripheral blood stem cells from human leukocyte antigen-matched related or unrelated donors as well as in recipients of grafts from human leukocyte antigen haploidentical donors. Copyright© Ferrata Storti Foundation.

  18. Myxoid chondrosarcoma of sphenoid bone

    Directory of Open Access Journals (Sweden)

    Amit K Chowhan

    2012-01-01

    Full Text Available The myxoid variant of chondrosarcoma is usually seen in soft tissues where it is known as chordoid sarcoma or parachordoma. Rarely, it involves bone and when it does, cranial bones are the preferred location. This tumor is frequently amalgamated with the chondroid variant of chordoma, especially when the lesion occurs in the sphenoid bone/spheno-occipital region, because of their similar clinical presentations, anatomical locations, radiological findings, and mistaken histopathological features. It is essential to distinguish myxoid chondrosarcoma from the chondroid variant of chordoma, because of the different treatment protocol and prognostic importance. We present such a location-based diagnostic dilemma, solved successfully with ancillary immunohistochemistry.

  19. Your Bones

    Science.gov (United States)

    ... the top are called the cervical (say: SIR-vih-kul) vertebrae. These bones are in the back ... purposes only. For specific medical advice, diagnoses, and treatment, consult your doctor. © 1995- The Nemours Foundation. All ...

  20. Bone Scan

    Science.gov (United States)

    ... posts Join Mayo Clinic Connect Bone scan About Advertisement Mayo Clinic does not endorse companies or products. ... a Job Site Map About This Site Twitter Facebook Google YouTube Pinterest Mayo Clinic is a not- ...

  1. Bone pain

    DEFF Research Database (Denmark)

    Frost, Charlotte Ørsted; Hansen, Rikke Rie; Heegaard, Anne-Marie

    2016-01-01

    Skeletal conditions are common causes of chronic pain and there is an unmet medical need for improved treatment options. Bone pain is currently managed with disease modifying agents and/or analgesics depending on the condition. Disease modifying agents affect the underlying pathophysiology...... of the disease and reduce as a secondary effect bone pain. Antiresorptive and anabolic agents, such as bisphosphonates and intermittent parathyroid hormone (1-34), respectively, have proven effective as pain relieving agents. Cathepsin K inhibitors and anti-sclerostin antibodies hold, due to their disease...... modifying effects, promise of a pain relieving effect. NSAIDs and opioids are widely employed in the treatment of bone pain. However, recent preclinical findings demonstrating a unique neuronal innervation of bone tissue and sprouting of sensory nerve fibers open for new treatment possibilities....

  2. Unrelated allogeneic stem-cell transplantation in adult patients – 10-year experience

    Directory of Open Access Journals (Sweden)

    Jožef Pretnar

    2012-12-01

    Conclusion: Unrelated allogeneic stem-cell transplantation is suitable for acute myeloblastic leukemias with unfavorable risk factors. However, results in acute lymphoblastic leukemia are worse. Unrelated transplantation is not efficient as salvage treatment for patients with recurrent disease after autologous transplantation or chemotherapy- resistant relapse.

  3. Lymph node tuberculosis after allogeneic haematopoietic stem cell transplantation: an atypical presentation of an uncommon complication.

    Science.gov (United States)

    Martín-Sánchez, Guillermo; Drake-Pérez, Marta; Rodriguez, José Luis; Yañez, Lucrecia; Insunza, Andrés; Richard, Carlos

    2015-01-01

    Mycobacterium tuberculosis infections are uncommon complications in the haematopoietic stem cell post-transplant period. Most cases are reactivations of latent infections affecting the lung. We present an atypical case of isolated lymph node tuberculosis after an allogeneic haematopoietic stem cell transplantation, which highlights the importance of having a high suspicion index, even in non-endemic countries.

  4. Graft-versus-host disease and graft-versus-tumor effects after allogeneic hematopoietic cell transplantation

    DEFF Research Database (Denmark)

    Storb, Rainer; Gyurkocza, Boglarka; Storer, Barry E

    2013-01-01

    We designed a minimal-intensity conditioning regimen for allogeneic hematopoietic cell transplantation (HCT) in patients with advanced hematologic malignancies unable to tolerate high-intensity regimens because of age, serious comorbidities, or previous high-dose HCT. The regimen allows the purest...

  5. Impact of Allogeneic Stem Cell Transplantation in First Complete Remission in Acute Myeloid Leukemia

    DEFF Research Database (Denmark)

    Østgård, Lene Sofie Granfeldt; Lund, Jennifer L; Nørgaard, Jan Maxwell

    2018-01-01

    To examine the outcome of allogeneic stem cell transplantation (HSCT) in first complete remission (CR1) compared to chemotherapy alone in a population-based setting, we identified a cohort of acute myeloid leukemia (AML) patients aged 15-70 years diagnosed between 2000-2014 in Denmark. Using...

  6. Intractable myoclonic seizures in an allogeneic stem cell transplant recipient: A rare case of myoclonic epilepsy

    Directory of Open Access Journals (Sweden)

    Anna Robuccio

    2015-01-01

    Discussion: Graft versus host disease occurs in 30–50% of allogenic hematopoietic stem cell transplant patients and may cause pharmacoresistant myoclonic epilepsy; however, the mechanisms by which GVHD leads to recurrent myoclonic seizures are not well understood (Lee, 2005 [1]. The paucity of clinical reports of such manifestation makes it difficult to diagnose and effectively manage these patients.

  7. Reconstructed human epidermis: absence of Langerhans cells and failure to stimulate allogeneic lymphocytes in vitro.

    Science.gov (United States)

    Bagot, M; Bertaux, B; Heslan, M; Coulomb, B; Dubertret, L

    1988-01-01

    Whole human skin can be reconstructed in vitro, using dermal equivalents made of fibroblasts in a collagen matrix. We recently described a new method of epidermalization of dermal equivalents, based on the insertion of punch biopsies and the migration of epidermal cells (EC) on the reconstructed dermis. In the present study, we show that no MHC class II or T6 positive Langerhans cells (LC) can be detected in this new epidermis. Functional studies with EC of this reconstructed epidermis show that these EC completely fail to induce proliferation of allogeneic lymphocytes in mixed epidermal cell lymphocyte reactions and to raise an allogeneic T cell response. In contrast, fresh EC from the same donors induce a strong proliferative and cytotoxic response of the same effector cells. Moreover, the addition of fresh LC-containing EC autologous to effector lymphocytes does not restore an allogeneic proliferative and cytotoxic response directed against class I different EC of the new epidermis. Such a non-immunogenic whole skin model composed of two compartments, dermis and epidermis, completely devoid of class II-bearing antigen presenting cells, is thus a very promising technique for allogeneic skin grafting in the treatment of burns. Images Fig. 1 PMID:2964953

  8. Allogeneic Mesenchymal Stem Cells Restore Endothelial Function in Heart Failure by Stimulating Endothelial Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Courtney Premer

    2015-05-01

    Interpretation: These findings reveal a novel mechanism whereby allogeneic, but not autologous, MSC administration results in the proliferation of functional EPCs and improvement in vascular reactivity, which in turn restores endothelial function towards normal in patients with HF. These findings have significant clinical and biological implications for the use of MSCs in HF and other disorders associated with endothelial dysfunction.

  9. Active Epstein-Barr virus infection after allogeneic stem cell transplantation : re-infection or reactivation?

    NARCIS (Netherlands)

    Meijer, E; Spijkers, S; Moschatsis, S; Boland, GJ; Thijsen, SFT; van Loon, AM; Verdonck, LF

    Recipients of allogeneic stem cell transplants (SCT) often show active Epstein-Barr virus (EBV) infection, which may progress to EBV-associated lymphoproliferative disorders. It is not known whether these EBV infections are true reactivations of the endogenous EBV strain or re-infections with an

  10. Gastrointestinal toxicity, systemic inflammation, and liver biochemistry in allogeneic hematopoietic stem cell transplantation

    Science.gov (United States)

    Liver toxicity is frequently seen in relation to allogeneic hematopoietic stem cell transplantation (HSCT), but pathogenesis and the risk factors are poorly understood. The purpose of this study was to investigate associations between liver toxicity, gastrointestinal toxicity, and levels of immune-r...

  11. Gastrointestinal toxicity, systemic inflammation, and liver biochemistry in allogeneic hematopoietic stem cell transplantation

    DEFF Research Database (Denmark)

    Jordan, Karina; Pontoppidan, Peter; Uhlving, Hilde Hylland

    2017-01-01

    Liver toxicity is frequently seen in relation to allogeneic hematopoietic stem cell transplantation (HSCT), but pathogenesis and the risk factors are poorly understood. The purpose of this study was to investigate associations between liver toxicity, gastrointestinal toxicity, and levels of immun...

  12. Pretransplant C-reactive protein as a prognostic marker in allogeneic stem cell transplantation

    DEFF Research Database (Denmark)

    Jordan, Karina Kwi Im; Christensen, Ib Jarle; Heilmann, Carsten

    2014-01-01

    We evaluated the prognostic role of baseline levels of C-reactive Protein (CRP) as well as CRP levels during conditioning in patients undergoing myeloablative allogeneic stem cell transplantation (SCT). Furthermore, we studied the impact of baseline clinical factors and conditioning regimens on CRP...

  13. The risks of using allogeneic cell lines for vaccine production : The example of Bovine Neonatal Pancytopenia

    NARCIS (Netherlands)

    Benedictus, Lindert; Bell, Charlotte R

    2017-01-01

    INTRODUCTION: Bovine neonatal pancytopenia (BNP) is a hemorrhagic disease that emerged in calves across Europe in 2007. Its occurrence is attributed to immunization of the calf's mother with a vaccine produced using an allogeneic cell line. Vaccine-induced alloantibodies specific for

  14. Risk factors for treatment failure after allogeneic transplantation of patients with CLL

    DEFF Research Database (Denmark)

    Schetelig, J; de Wreede, L C; van Gelder, M

    2017-01-01

    For young patients with high-risk CLL, BTK-/PI3K-inhibitors or allogeneic stem cell transplantation (alloHCT) are considered. Patients with a low risk of non-relapse mortality (NRM) but a high risk of failure of targeted therapy may benefit most from alloHCT. We performed Cox regression analyses ...

  15. The Role of Allogeneic Transplantation in the Treatment of Multiple Myeloma.

    Science.gov (United States)

    Majolino, I

    1998-01-01

    In multiple myeloma (MM) attempts to improve upon the results of standard melphalanpredisone with other conventional dose drug combinations, have generally been unsuccessful, producing only minor improvements in response rate, with little effect on survival. The only treatment capable of producing a dramatic change in response and life expectancy is high-dose chemo-radiotherapy followed by stem cell transplantation. However, after autologous transplant relapse will almost inevitably occur, and freedom from recurrence curves show no plateau in most studies. Besides the resistance of the disease to chemotherapy, another possible explanation is tumor contamination of the graft. This is one major advantage of allogeneic transplantation over autologous, the other being an immune mediated mechanism of tumor suppression in part related to GVHD. Application of allogeneic transplantation to MM has met a number of obstacles, but is now entering a phase of reappraisal, due in part to a tendency to earlier transplantation, in part to the use of novel technologies such as allogeneic peripheral blood stem cells instead of marrow. The goal should be the reduction of transplant related deaths, to better exploit the higher eradication potential of allogeneic cell therapies. The most intriguing perspectives are those related to immune manipulation of recipient and/or donor.

  16. Blood management in total hip replacement: an analysis of factors associated with allogenic blood transfusion.

    Science.gov (United States)

    Wong, Samuel; Tang, Howard; de Steiger, Richard

    2015-06-01

    The aim of this study was to audit the blood transfusion practice throughout the Epworth Healthcare Hospitals for patients undergoing primary total hip replacement (THR). We determined if blood-saving techniques were having an impact on the risk of allogenic blood transfusion and which patients were at risk of receiving allogenic blood transfusion. This study uses a retrospective audit of 787 patients who had undergone primary THR surgery at three Melbourne hospitals: Epworth Richmond, Epworth Eastern and Epworth Freemasons in 2010. Patient demographics, transfusion requirements and blood-conserving techniques were recorded. One hundred and eighty (23%) patients received allogenic blood transfusion and 18 (2.3%) patients received autologous blood transfusion. On multivariate analysis, preoperative anaemia (odds ratio (OR) 4.7, P blood transfusion. Use of spinal anaesthetic was found to be associated with lower risk of transfusion (OR 0.6, P = 0.0180) compared with general anaesthetic alone. Cell saver, acute normovolaemic haemodilution and re-infusion drain tube usage did not have a significant impact on reducing the risk of allogenic blood transfusion. Identification of patients at risk of blood transfusion, correction of preoperative anaemia and a restrictive transfusion policy are important factors to consider in effective perioperative blood management. © 2015 Royal Australasian College of Surgeons.

  17. Preoperative Acute Normovolemic Hemodilution for Minimizing Allogeneic Blood Transfusion: A Meta-Analysis.

    Science.gov (United States)

    Zhou, Xuelong; Zhang, Chenjing; Wang, Yin; Yu, Lina; Yan, Min

    2015-12-01

    Previous studies have evaluated the efficacy of preoperative acute normovolemic hemodilution (PANH) in reducing the need for allogeneic blood transfusion. However, the results to date have been controversial. In this study, we sought to reassess the efficacy and safety of PANH based on newly emerging evidence. Medline, EMBASE, ISI Web of Knowledge, and Cochrane Central Register of Controlled Trials databases were searched using the key words "hemodilution," "autotransfusion," or "hemorrhage" to retrieve all randomized controlled trials examining the benefits of PANH compared with control patients not undergoing PANH in any type of surgery. Sixty-three studies involving 3819 patients were identified. The risk of requiring an allogeneic blood transfusion and the overall volume of allogeneic red blood cell transfused during the perioperative period were reduced in the PANH group compared with the control group (relative risk, 0.74; 95% confidence interval, 0.63 to 0.88; P = 0.0006; weighted mean difference, -0.94 units; 95% confidence interval, -1.27 to -0.61 units; P transfusion. Perioperative blood loss, adverse events, and the length of hospitalization were comparable between these groups. Although these results suggest that PANH is effective in reducing allogeneic blood transfusion, we identified significant heterogeneity and publication bias, which raises concerns about the true efficacy of PANH.

  18. Transfusion associated complications in cardiac surgery : the swan song of the allogeneic leukocytes ?

    NARCIS (Netherlands)

    Bilgin, Memiş Yavuz

    2011-01-01

    In the Netherlands 1 of 1.000 inhibitants undergo cardiac surgery annually. To compensate blood loss these patients receive often blood transfusions, which can cause unexpected adverse reactions. Allogeneic leukocytes may play a prominent role in the development of these adverse reactions. We found

  19. Quantitative study of new bone formation in distraction osteogenesis of craniofacial bones by bone scintigraphy.

    Science.gov (United States)

    Rojvachiranonda, Nond; Tepmongkol, Supatporn; Mahatumarat, Charan

    2007-09-01

    Although distraction osteogenesis is widely accepted as a technique to augment the craniofacial skeleton, timing to start distraction after an osteotomy or to remove distractors is basically based on studies on long bones. Because bone scintigraphy is well known to be the gold standard for quantitative measurement of bone formation, we conducted this pilot study to evaluate its feasibility as a tool for assessing new bone formation by distraction osteogenesis. Five patients with midface hypoplasia and four with mandibular hypoplasia were studied. Each patient had five bone scans: before surgery, 3 and 30 days after stopping distraction, and 3 days before and 3 months after distractor removal. Radiotracer uptake values at distraction sites were measured at 1 and 3 hours. Each uptake value was compared with preoperative study as uptake ratio. A typical pattern of radiotracer uptake ratio was observed in all cases with successful distraction. Uptake rose to the maximum during the consolidation period and remained at or above the preoperative level until the study end point. In one patient who had mandibular distraction and nonunion of the right ramus, there was no uptake peak during early consolidation as seen in the successfully distracted body and in the other cases. Bone scintigraphy was found to be a useful investigation in craniofacial distraction. It showed the dynamic of new bone formation by demonstrating the osteoblastic activity, which is important objective information for determining distraction rate and consolidation duration in each case. It may also be a tool that can predict the outcome of distraction osteogenesis.

  20. Effects of supralethal total body irradiation and bone marrow reconstitution upon immunologic memory

    Energy Technology Data Exchange (ETDEWEB)

    Akiyama, N.; Bachvaroff, R.J.; Sato, T.; Rapaport, F.T.

    1981-03-01

    The transplantation of bone marrow from prospectively selected genotypically and pedigree DLA-identical donors into supralethally irradiated littermate and nonlittermate recipients within the Copperstown beagle colony has regularly resulted in the establishment of long-term chimerism, with no evidence of graft-versus-host disease in the recipients. It has been demonstrated that irradiated recipients exhibit significant decreases in their ability to muster primary immunological responses during the first months after reconstitution with bone marrow. Beyond the documented capacity of preirradiation blood transfusions to interfere with subsequent engraftment of allogeneic marrow, however, there have been no systematic studies of the possible effects of irradiation and bone marrow transplantation upon immunologic memory. The present study was designed in order to assess this question in greater detail, with particular regard to the effects of irradiation and bone marrow reconstitution upon host sensitization to skin allografts. The results indicate that, within the experimental limitations described, the state of sensitivity produced by first set skin allograft rejection is not affected significantly by supralethal total body irradiation and reconstitution of the recipient with allogeneic bone marrow.

  1. Successful ageing

    DEFF Research Database (Denmark)

    Kusumastuti, Sasmita; Derks, Marloes G. M.; Tellier, Siri

    2016-01-01

    on the objective measurements as determined by researchers. Subsequent sub-clustering analysis pointed to different domains of functioning and various ways of assessment. CONCLUSION: In the current literature two mutually exclusive concepts of successful ageing are circulating that depend on whether the individual......BACKGROUND: Ageing is accompanied by an increased risk of disease and a loss of functioning on several bodily and mental domains and some argue that maintaining health and functioning is essential for a successful old age. Paradoxically, studies have shown that overall wellbeing follows...... a curvilinear pattern with the lowest point at middle age but increases thereafter up to very old age. OBJECTIVE: To shed further light on this paradox, we reviewed the existing literature on how scholars define successful ageing and how they weigh the contribution of health and functioning to define success...

  2. ATMPs: A Guide for Bone Marrow-derived MSCs Application in Bone and Cartilage Tissue Engineering.

    Science.gov (United States)

    Confalonieri, Davide; Schwab, Andrea; Walles, Heike; Ehlicke, Franziska

    2017-10-07

    Millions of people worldwide suffer from trauma- or age-related orthopedic diseases such as osteoarthritis, osteoporosis or cancer. Tissue Engineering and Regenerative Medicine are multidisciplinary fields focusing on the development of artificial organs, biomimetic engineered tissues and cells to restore or maintain tissue and organ function. While allogenic and future autologous transplantations are nowadays the gold standards for both cartilage and bone defect repair, they are both subject to important limitations such as availability of healthy tissue, donor site morbidity and graft rejection. Tissue engineered bone and cartilage products represent a promising and alternative approach with the potential to overcome these limitations. Since the development of Advanced Therapy Medicinal Products (ATMPs) such as Tissue Engineering products requires the knowledge of diverse regulation and an extensive communication with the national / international authorities, the aim of this review is therefore to summarize the state-of-the-art on the clinical applications of human bone marrow-derived stromal cells for cartilage and bone Tissue Engineering. In addition, this review provides an overview of the European legislation in order to facilitate the development and commercialization of new ATMPs.

  3. Medicines and Bone Loss

    Science.gov (United States)

    Fact Sheet Medici a ne n s d Bone Loss Some types of medicines can cause bone loss, making your bones weak, if used for a long time. Use over a short time ... old bone and replaces it with new bone. Bone loss occurs when old bone breaks down faster than ...

  4. Automated radiogrammetry is a feasible method for measuring bone quality and bone maturation in severely disabled children

    Energy Technology Data Exchange (ETDEWEB)

    Mergler, Sandra [Erasmus MC, Department of General Practice and Intellectual Disability Medicine, University Medical Centre, Rotterdam (Netherlands); Care and Service Centre for People with Intellectual Disabilities, Medical Department ASVZ, Sliedrecht (Netherlands); Man, Stella A. de [Amphia Hospital, Department of Paediatrics, Breda (Netherlands); Boot, Annemieke M. [University of Groningen, Department of Paediatric Endocrinology, University Medical Centre Groningen, Groningen (Netherlands); Heus, Karen G.C.B.B. [Erasmus MC, Department of General Paediatrics, Sophia Children' s Hospital, University Medical Centre, Rotterdam (Netherlands); Huijbers, Wim A.R. [Beatrix Hospital, Department of Paediatrics, Gorinchem (Netherlands); Rijn, Rick R. van [Emma Children' s Hospital/Academic Medical Centre, Department of Radiology, Amsterdam (Netherlands); Penning, Corine; Evenhuis, Heleen M. [Erasmus MC, Department of General Practice and Intellectual Disability Medicine, University Medical Centre, Rotterdam (Netherlands)

    2016-06-15

    Children with severe neurological impairment and intellectual disability are prone to low bone quality and fractures. We studied the feasibility of automated radiogrammetry in assessing bone quality in this specific group of children. We measured outcome of bone quality and, because these children tend to have altered skeletal maturation, we also studied bone age. We used hand radiographs obtained in 95 children (mean age 11.4 years) presenting at outpatient paediatric clinics. We used BoneXpert software to determine bone quality, expressed as paediatric bone index and bone age. Regarding feasibility, we successfully obtained a paediatric bone index in 60 children (63.2%). The results on bone quality showed a mean paediatric bone index standard deviation score of -1.85, significantly lower than that of healthy peers (P < 0.0001). Almost 50% of the children had severely diminished bone quality. In 64% of the children bone age diverged more than 1 year from chronological age. This mostly concerned delayed bone maturation. Automated radiogrammetry is feasible for evaluating bone quality in children who have disabilities but not severe contractures. Bone quality in these children is severely diminished. Because bone maturation frequently deviated from chronological age, we recommend comparison to bone-age-related reference values. (orig.)

  5. Successful ageing

    DEFF Research Database (Denmark)

    Bülow, Morten Hillgaard; Söderqvist, Thomas

    2014-01-01

    Since the late 1980s, the concept of ‘ successful ageing’ has set the frame for discourse about contemporary ageing research. Through an analysis of the reception to John W. Rowe and Robert L. Kahn's launch of the concept of ‘ successful ageing’ in 1987, this article maps out the important themes...... strategies; and the importance of individual, societal and scientific conceptualisations and understandings of ageing. By presenting an account of the recent historical uses, interpretations and critiques of the concept, the article unfolds the practical and normative complexities of ‘ successful ageing’....... and discussions that have emerged from the interdisciplinary field of ageing research. These include an emphasis on interdisciplinarity; the interaction between biology, psycho-social contexts and lifestyle choices; the experiences of elderly people; life-course perspectives; optimisation and prevention...

  6. Citation Success

    DEFF Research Database (Denmark)

    Vaio, Gianfranco Di; Waldenström, Daniel; Weisdorf, Jacob Louis

    2012-01-01

    This study examines the determinants of citation success among authors who have recently published their work in economic history journals. Besides offering clues about how to improve one's scientific impact, our citation analysis also sheds light on the state of the field of economic history....... Consistent with our expectations, we find that full professors, authors appointed at economics and history departments, and authors working in Anglo-Saxon and German countries are more likely to receive citations than other scholars. Long and co-authored articles are also a factor for citation success. We...... find similar patterns when assessing the same authors' citation success in economics journals. As a novel feature, we demonstrate that the diffusion of research — publication of working papers, as well as conference and workshop presentations — has a first-order positive impact on the citation rate....

  7. Citation Success

    DEFF Research Database (Denmark)

    Di Vaio, Gianfranco; Waldenström, Daniel; Weisdorf, Jacob Louis

    This study analyses determinants of citation success among authors publishing in economic history journals. Bibliometric features, like article length and number of authors, are positively correlated with the citation rate up to a certain point. Remarkably, publishing in top-ranked journals hardly...... affects citations. In regard to author-specific characteristics, male authors, full professors and authors working economics or history departments, and authors employed in Anglo-Saxon countries, are more likely to get cited than others. As a ‘shortcut' to citation success, we find that research diffusion...

  8. Route of delivery influences biodistribution of human bone marrow-derived mesenchymal stromal cells following experimental bone marrow transplantation

    Directory of Open Access Journals (Sweden)

    Wang FJ

    2015-12-01

    Full Text Available Mesenchymal stromal cells (MSCs have shown promise as treatment for graft-versus-host disease (GvHD following allogeneic bone marrow transplantation (alloBMT. Mechanisms mediating in vivo effects of MSCs remain largely unknown, including their biodistribution following infusion. To this end, human bone-marrow derived MSCs (hMSCs were injected via carotid artery (IA or tail vein (TV into allogeneic and syngeneic BMT recipient mice. Following xenogeneic transplantation, MSC biodistribution was measured by bioluminescence imaging (BLI using hMSCs transduced with a reporter gene system containing luciferase and by scintigraphic imaging using hMSCs labeled with [99mTc]-HMPAO. Although hMSCs initially accumulated in the lungs in both transplant groups, more cells migrated to organs in alloBMT recipient as measured by in vivo BLI and scintigraphy and confirmed by ex vivo BLI imaging, immunohistochemistry and quantitative RT-PCR. IA injection resulted in persistent whole–body hMSC distribution in alloBMT recipients, while hMSCs were rapidly cleared in the syngeneic animals within one week. In contrast, TV-injected hMSCs were mainly seen in the lungs with fewer cells traveling to other organs. Summarily, these results demonstrate the potential use of IA injection to alter hMSC biodistribution in order to more effectively deliver hMSCs to targeted tissues and microenvironments.

  9. Disseminated cutaneous trichosporonosis in an adult bone marrow transplant patient

    Directory of Open Access Journals (Sweden)

    A. M. Y. Yong

    2017-01-01

    Full Text Available The Trichosporon species are yeast-like opportunistic pathogens in immunocompromised patients. Trichosporon asahii infections have been reported in pediatric bone marrow transplant (BMT patients. However, its incidence is low in the adult literature. A 52-year-old Chinese woman who was diagnosed with acute myeloid leukemia received induction chemotherapy and underwent allogenic bone marrow transplant, which was complicated by a relapse and required salvage chemotherapy. She developed persistent non-neutropenic fever secondary to presumed hepatosplenic candidiasis. Antifungal therapy with fluconazole and anidulafungin was administered. She remained febrile and tender dusky nodules appeared over all the four limbs. Histopathological examination and fungal culture identified T. asahii. Oral voriconazole was initiated with complete resolution of her lesions. The Trichosporon species is a frequently isolated yeast species from cancer patients. Voriconazole has become the first choice agent against Trichosporon. We highlight the increased awareness and clinical suspicion required for diagnosis and subsequent management in similar adult patients.

  10. [Varicella zoster virus infection after bone marrow transplant. Unusual presentation and importance of prevention].

    Science.gov (United States)

    Ladrière, M; Bibes, B; Rabaud, C; Delaby, P; May, T; Canton, P

    Leukemeia and lymphoproliferative disease are associated with a high risk of varicela-zoster virus (VZV) infection. Although infrequent, visceral involvement can be fatal. We report two cases of patients presenting severe VZV infection after bone marrow transplantation. The first patient was a 42-year old man who received an allogeneic bone marrow transplantation for chronic myelogenous leukemia. A severe graft-versus-host reaction occurred. Three months after discontinuing VZV prophylaxis, VZV transverse myelitis was diagnosed, leading to death despite prompt treatment with acyclovir. The second patient was a 42-year-old woman treated with autologous bone marrow transplantation for lymphoma. She developed acute viral pancreatitis one month after discontinuing VZV prophylaxis. Recovery was achieved with intravenous treatment. These two cases illustrate the potential gravity of VZV infection after bone marrow transplantation. These observations point to the need for revisiting the duration of VZV prophylaxis.

  11. Bone mineral content and bone metabolism in young adults with severe periodontitis

    DEFF Research Database (Denmark)

    Wowern von, N.; Westergaard, J.; Kollerup, G.

    2001-01-01

    Bone loss, bone markers, bone metabolism, bone mineral content, osteoporosis, severe periodontitis......Bone loss, bone markers, bone metabolism, bone mineral content, osteoporosis, severe periodontitis...

  12. The Outcome of Allogeneic Hematopoietic Stem Cell Transplantation for Myelofibrosis: a Retrospective Study in a Single Center

    Directory of Open Access Journals (Sweden)

    Mei-Fang Hou

    2015-03-01

    Conclusions: Allogeneic hematopoietic stem cell transplantation is effective in treating myelofibrosis and is associated with modest toxicity and post-transplantation complications. In order to improve the treatment outcome, we have to manage GVHD and infection more carefully.

  13. Associations between levels of insulin-like growth factor 1 and sinusoidal obstruction syndrome after allogeneic haematopoietic stem cell transplantation

    DEFF Research Database (Denmark)

    Weischendorff, Sarah; Kielsen, Katrine; Sengeløv, H

    2017-01-01

    Allogeneic myeloablative haematopoietic stem cell transplantation (HSCT) is challenged by severe adverse events, as cytotoxic effects of the conditioning may result in systemic inflammation, leaky epithelial barriers and organ toxicities, contributing to treatment-related morbidity and mortality...

  14. Demineralized Bone Matrix to Augment Tendon-Bone Healing: A Systematic Review.

    Science.gov (United States)

    Hexter, Adam T; Pendegrass, Catherine; Haddad, Fares; Blunn, Gordon

    2017-10-01

    justified, research is required that determines the best source of DBM (allogenic vs xenogenic) and the best form of DBM (demineralized cortical bone vs DBM paste) to be used in them.

  15. Bone Loss in IBD

    Science.gov (United States)

    ... Home > Resources > Bone Loss in IBD Go Back Bone Loss in IBD Email Print + Share As many as ... halt bone loss are so important. CAUSES OF BONE LOSS IN IBD Experts point to several suspected causes ...

  16. Ultrasonic Evaluation of Deeply Located Trabecular Bones - Preliminary Results

    Science.gov (United States)

    Cieślik, Lucyna; Litniewski, Jerzy

    The analysis of ultrasonic signals scattered by soft tissues have been successfully applied for their characterization. Similarly, the trabecular bone backscattered signal contains information about the properties of the bone structure. Therefore scattering-based ultrasonic technique potentially enables the assessment of microstructure characteristics of a bone. The femoral neck fracture often occurs in the course of osteoporosis and can lead to severe complications. Therefore assessment of femoral bone microstructure and condition is important and essential for the diagnosis and treatment monitoring. As far most of the trabecular bone investigations have been performed in vitro. The only in vivo measurements were carried out in transmission and mostly concerned estimation of the attenuation in heel bone. We have built the ultrasonic scanner that could be useful in acquiring the RF (Radio Frequency) echoes backscattered by the trabecular bone in vivo. Moreover, the bone scanner provides data not only from heel bone but from deeply located bones as well (e.g. femoral bone). It can be also used for easily accessible bones like heel bone or breastbone. In this case a gel-pad is applied to assure focusing of ultrasound in trabecular bone (approximately 10 mm beneath the cortical bone). This study presents preliminary results of the attenuating properties evaluation of trabecular bone from the ultrasonic echoes backscattered by heel bone and femoral neck.

  17. Impact of pre-transplant depression on outcomes of allogeneic and autologous hematopoietic stem cell transplantation.

    Science.gov (United States)

    El-Jawahri, Areej; Chen, Yi-Bin; Brazauskas, Ruta; He, Naya; Lee, Stephanie J; Knight, Jennifer M; Majhail, Navneet; Buchbinder, David; Schears, Raquel M; Wirk, Baldeep M; Wood, William A; Ahmed, Ibrahim; Aljurf, Mahmoud; Szer, Jeff; Beattie, Sara M; Battiwalla, Minoo; Dandoy, Christopher; Diaz, Miguel-Angel; D'Souza, Anita; Freytes, Cesar O; Gajewski, James; Gergis, Usama; Hashmi, Shahrukh K; Jakubowski, Ann; Kamble, Rammurti T; Kindwall-Keller, Tamila; Lazarus, Hilard M; Malone, Adriana K; Marks, David I; Meehan, Kenneth; Savani, Bipin N; Olsson, Richard F; Rizzieri, David; Steinberg, Amir; Speckhart, Dawn; Szwajcer, David; Schoemans, Helene; Seo, Sachiko; Ustun, Celalettin; Atsuta, Yoshiko; Dalal, Jignesh; Sales-Bonfim, Carmem; Khera, Nandita; Hahn, Theresa; Saber, Wael

    2017-05-15

    To evaluate the impact of depression before autologous and allogeneic hematopoietic cell transplantation (HCT) on clinical outcomes post-transplantation. We analyzed data from the Center for International Blood and Marrow Transplant Research to compare outcomes after autologous (n = 3786) or allogeneic (n = 7433) HCT for adult patients with hematologic malignancies with an existing diagnosis of pre-HCT depression requiring treatment versus those without pre-HCT depression. Using Cox regression models, we compared overall survival (OS) between patients with or without depression. We compared the number of days alive and out of the hospital in the first 100 days post-HCT using Poisson models. We also compared the incidence of grade 2-4 acute and chronic graft-versus-host disease (GVHD) in allogeneic HCT. The study included 1116 (15%) patients with pre-transplant depression and 6317 (85%) without depression who underwent allogeneic HCT between 2008 and 2012. Pre-transplant depression was associated with lower OS (hazard ratio [HR], 1.13; 95% confidence interval [CI], 1.04-1.23; P = 0.004) and a higher incidence of grade 2-4 acute GVHD (HR, 1.25; 95% CI, 1.14-1.37; P Pre-transplant depression was associated with fewer days-alive-and-out-of-the hospital (means ratio [MR] = 0.97; 95% CI, 0.95-0.99; P = 0.004). There were 512 (13.5%) patients with Pre-transplant depression and 3274 (86.5%) without depression who underwent autologous HCT. Pre-transplant depression in autologous HCT was not associated with OS (HR, 1.15; 95% CI, 0.98-1.34; P = 0.096) but was associated with fewer days alive and out of the hospital (MR, 0.98; 95% CI, 0.97-0.99; P = 0.002). Pre-transplant depression was associated with lower OS and higher risk of acute GVHD among allogeneic HCT recipients and fewer days alive and out of the hospital during the first 100 days after autologous and allogeneic HCT. Patients with pre-transplant depression represent a population that is

  18. Functional autoantibodies against SSX-2 and NY-ESO-1 in multiple myeloma patients after allogeneic stem cell transplantation.

    Science.gov (United States)

    Luetkens, Tim; Kobold, Sebastian; Cao, Yanran; Ristic, Marina; Schilling, Georgia; Tams, Sinje; Bartels, Britta Marlen; Templin, Julia; Bartels, Katrin; Hildebrandt, York; Yousef, Sara; Marx, Andreas; Haag, Friedrich; Bokemeyer, Carsten; Kröger, Nicolaus; Atanackovic, Djordje

    2014-11-01

    Multiple myeloma (MM) is the malignancy with the most frequent expression of the highly immunogenic cancer-testis antigens (CTA), and we have performed the first analysis of longitudinal expression, immunological properties, and fine specificity of CTA-specific antibody responses in MM. Frequency and characteristics of antibody responses against cancer-testis antigens MAGE-A3, NY-ESO-1, PRAME, and SSX-2 were analyzed using peripheral blood (N = 1094) and bone marrow (N = 200) plasma samples from 194 MM patients. We found that antibody responses against CTA were surprisingly rare, only 2.6 and 3.1 % of patients evidenced NY-ESO-1- and SSX-2-specific antibodies, respectively. NY-ESO-1-specific responses were observed during disease progression, while anti-SSX-2 antibodies appeared after allogeneic stem cell transplantation and persisted during clinical remission. We found that NY-ESO-1- and SSX-2-specific antibodies were both capable of activating complement and increasing CTA uptake by antigen-presenting cells. SSX-2-specific antibodies were restricted to IgG3, NY-ESO-1 responses to IgG1 and IgG3. Remarkably, NY-ESO-1-positive sera recognized various non-contiguous regions, while SSX-2-specific responses were directed against a single 6mer epitope, SSX-2(85-90). We conclude that primary autoantibodies against intracellular MM-specific tumor antigens SSX-2 and NY-ESO-1 are rare but functional. While their contribution to disease control still remains unclear, our data demonstrate their theoretic ability to affect cellular anti-tumor immunity by formation and uptake of mono- and polyvalent immune complexes.

  19. Central and peripheral nervous system immune mediated demyelinating disease after allogeneic hemopoietic stem cell transplantation for hematologic disease.

    Science.gov (United States)

    Delios, Anna Maria; Rosenblum, Marc; Jakubowski, Ann A; DeAngelis, Lisa M

    2012-11-01

    Immune mediated demyelinating disease (IMDD) after allogeneic hemopoietic stem cell transplant (HSCT) is rare and its etiology unclear. In this retrospective study, we identified patients who underwent HSCT between January 1992 and December 2010 and had IMDD post transplant. A total of 1,484 patients received HSCT and 7 (0.5 %) suffered from IMDD; five were men, and the median age was 54 years (range, 29-64 years). HSCT treated acute myeloid leukemia (n = 5), myelodysplastic syndrome (n = 1), and Waldenström macroglobulinemia (n = 1). All received an HLA matched donor graft, related (6), unrelated (1); from the bone marrow (1), peripheral blood stem cell (6); and T-cell depleted, ex vivo (6) or in vivo (1). The median time from transplant to neurologic symptoms was 120 days (range, 60-390 days). Three had acute demyelinating encephalomyelitis (ADEM), three acute inflammatory demyelinating polyradiculopathy (AIDP) and one autonomic neuropathy. Four of six patients tested had hemopoietic mixed chimerism prior to neurologic symptoms and low CD4(+) T-cell counts, median 76 (15-500 cells/μL). Two patients had simultaneous systemic graft versus host disease (GVHD). Two patients with ADEM had a spinal cord or brain biopsy which revealed demyelination. No patients had a viral etiology identified in the cerebrospinal fluid. Patients were treated with IV immunoglobulin, high dose steroids and/or rituximab. Five patients had a significant recovery. Response to immune modulators suggests an immune-based etiology. The incidence of de novo autoimmune disease after HSCT for hematological diseases is rare and may be difficult to differentiate from GVHD.

  20. Excellent outcome of allogeneic hematopoietic SCT with reduced-intensity conditioning for the treatment of chronic active EBV infection.

    Science.gov (United States)

    Kawa, K; Sawada, A; Sato, M; Okamura, T; Sakata, N; Kondo, O; Kimoto, T; Yamada, K; Tokimasa, S; Yasui, M; Inoue, M

    2011-01-01

    Since we reported the first successful case of allogeneic hematopoietic SCT (allo-HSCT), we have performed allo-HSCT for 29 patients with chronic active EBV infection (CAEBV), using either myeloablative conditioning (MAC) allo-HSCT (MAST) or reduced-intensity conditioning (RIC) allo-HSCT (RIST). In this retrospective analysis we compared the outcomes after MAST and RIST to identify the optimal conditioning for patients with CAEBV. Of 29 patients, 11 underwent allo-HSCT with MAC, consisting of TBI (12 Gy), etoposide (900 mg/m²) and CY (120 mg/kg) or melphalan (210 mg/m²), and the remaining 18 patients received allo-HSCT after RIC, consisting of fludarabine (∼ 180 mg/m²) and melphalan (140 mg/m²) or CY (120 mg/kg), with/without antithymocyte globulin and low-dose irradiation. Donor sources were 8 related BM, 2 related peripheral blood, 5 CD34 selected cells from HLA-haploidentical donors, 8 unrelated BM and 8 unrelated cord blood. The 3-year-EFS rate was 54.5 ± 15.0% for MAST group and 85.0 ± 8.0% for RIST group, and the 3-year OS rate was 54.5 ± 15.0% for MAST group and 95.0 ± 4.9% for RIST group (P = 0.016). Allo-HSCT after RIC seems to be a promising approach for the treatment of CAEBV.

  1. Serial in vivo imaging of transplanted allogeneic neural stem cell survival in a mouse model of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Srivastava, Amit K; Gross, Sarah K; Almad, Akshata A; Bulte, Camille A; Maragakis, Nicholas J; Bulte, Jeff W M

    2017-03-01

    Neural stem cells (NSCs) are being investigated as a possible treatment for amyotrophic lateral sclerosis (ALS) through intraspinal transplantation, but no longitudinal imaging studies exist that describe the survival of engrafted cells over time. Allogeneic firefly luciferase-expressing murine NSCs (Luc+-NSCs) were transplanted bilaterally (100,000 cells/2μl) into the cervical spinal cord (C5) parenchyma of pre-symptomatic (63day-old) SOD1G93A ALS mice (n=14) and wild-type age-matched littermates (n=14). Six control SOD1G93A ALS mice were injected with saline. Mice were immunosuppressed using a combination of tacrolimus+sirolimus (1mg/kg each, i.p.) daily. Compared to saline-injected SOD1G93A ALS control mice, a transient improvement (pALS mice at the time of disease onset (71.7±17.9% at 4weeks post-transplantation, pALS mice, poor cell survival was accompanied by accumulation of mature macrophages and the presence of astrogliosis and microgliosis. We conclude that the disease progression adversely affects the survival of engrafted murine Luc+-NSCs in SOD1G93A ALS mice as a result of the hostile ALS spinal cord microenvironment, further emphasizing the challenges that face successful cell therapy of ALS. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Decellularized allogeneic and xenogeneic tissue as a bioscaffold for regenerative medicine: factors that influence the host response.

    Science.gov (United States)

    Badylak, Stephen F

    2014-07-01

    Biologic scaffold materials composed of mammalian extracellular matrix (ECM) are prepared by decellularization of source tissues harvested from either humans (allogeneic) or a variety of other (xenogeneic) species. These matrix scaffold materials are commonly regulated and used as surgical mesh materials for applications such as ventral hernia repair, musculotendinous tissue reconstruction, dura mater replacement, reconstructive breast surgery, pelvic floor reconstruction, and the treatment of cutaneous ulcers, among others. The clinical results for these applications vary widely for reasons which include characteristics of the source tissue, methods and efficacy of tissue decellularization, and methods of processing/manufacturing. However, the primary determinant of success or failure in the clinical setting is the response of the host to these implanted biologic scaffold materials. It is logical to question why any non-self biologic material, particularly a xenogeneic material, would not elicit an early and aggressive adverse immune response. The present manuscript briefly describes the known mechanisms by which these biologic scaffold materials can facilitate a constructive remodeling response, the known causative factors of an adverse response, and provides a general discussion of the role of the macrophage in determining outcome.

  3. Treatment of Temporal Bone Fractures.

    Science.gov (United States)

    Diaz, Rodney C; Cervenka, Brian; Brodie, Hilary A

    2016-10-01

    Traumatic injury to the temporal bone can lead to significant morbidity or mortality and knowledge of the pertinent anatomy, pathophysiology of injury, and appropriate management strategies is critical for successful recovery and rehabilitation of such injured patients. Most temporal bone fractures are caused by motor vehicle accidents. Temporal bone fractures are best classified as either otic capsule sparing or otic capsule disrupting-type fractures, as such classification correlates well with risk of concomitant functional complications. The most common complications of temporal bone fractures are facial nerve injury, cerebrospinal fluid (CSF) leak, and hearing loss. Assessment of facial nerve function as soon as possible following injury greatly facilitates clinical decision making. Use of prophylactic antibiotics in the setting of CSF leak is controversial; however, following critical analysis and interpretation of the existing classic and contemporary literature, we believe its use is absolutely warranted.

  4. Treatment of Temporal Bone Fractures

    Science.gov (United States)

    Diaz, Rodney C.; Cervenka, Brian; Brodie, Hilary A.

    2016-01-01

    Traumatic injury to the temporal bone can lead to significant morbidity or mortality and knowledge of the pertinent anatomy, pathophysiology of injury, and appropriate management strategies is critical for successful recovery and rehabilitation of such injured patients. Most temporal bone fractures are caused by motor vehicle accidents. Temporal bone fractures are best classified as either otic capsule sparing or otic capsule disrupting-type fractures, as such classification correlates well with risk of concomitant functional complications. The most common complications of temporal bone fractures are facial nerve injury, cerebrospinal fluid (CSF) leak, and hearing loss. Assessment of facial nerve function as soon as possible following injury greatly facilitates clinical decision making. Use of prophylactic antibiotics in the setting of CSF leak is controversial; however, following critical analysis and interpretation of the existing classic and contemporary literature, we believe its use is absolutely warranted. PMID:27648399

  5. Effectiveness of allogeneic CD3AK cells on transplanted human renal cell cancer in mice with severe combined immune deficiency.

    Science.gov (United States)

    Ge, Lei; Shan, Zhongjie; Han, Qianhe; Zhang, Nan; Zhao, Yang

    2016-01-01

    To assess the activity of allogeneic anti-CD3 antibody induced activated killer (CD3AK) cells on transplanted human renal cell cancer (RCC) in mice with severe combined immune deficiency (SCID), thus to provide theoretical and experimental support for clinical application of allogeneic CD3AK cells in the treatment of RCC. A culture system which can massively increase allogeneic CD3AK cells was constructed. CCK-8 method was used to detect lethal effect of allogeneic CD3AK cells on human OS-RC-2 renal cancer cell line. Then, tumor-bearing mice models were constructed. SCID mice were randomly divided into four groups: group A (caudal vein was injected with allogeneic CD3AK cells before tumor bearing), group B (the control group of group A: caudal vein was injected with PBS before tumor bearing), group C (caudal vein was injected with allogeneic CD3AK cells after tumor bearing) and group D (the control group of group C: caudal vein was injected with PBS after tumor bearing), and spleen parameters were calculated to observe any inhibitory effect of allogeneic CD3AK cells on the growth of renal cancer cells, as well as their effect on the immune system of mice. Compared with the control groups B and D, spleen parameters of groups A and C increased significantly (p0.05); compared with the control groups B and D, tumor weight of groups A and C decreased significantly and tumors grew slowly (pcancer in mice with SCID. Also CD3AK cells expressed certain preventive effect on the development of implanted cancer in SCID mice; allogeneic CD3AK cells possessed antitumor activity and could enhance the immunologic functions of SCID mice with human renal cell-bearing cancer.

  6. Bone regeneration in sinus lifts: comparing tissue-engineered bone and iliac bone.

    Science.gov (United States)

    Voss, Pit; Sauerbier, Sebastian; Wiedmann-Al-Ahmad, Margit; Zizelmann, Christoph; Stricker, Andres; Schmelzeisen, Rainer; Gutwald, Ralf

    2010-03-01

    Lifting of the sinus floor is a standard procedure for bony augmentation that enables dental implantation. Although cultivated skin and mucosal grafts are often used in plastic and maxillofacial surgery, tissue-engineered bone has not achieved the same success. We present the clinical results of dental implants placed after the insertion of periosteum-derived, tissue-engineered bone grafts in sinus lifts. Periosteal cells were isolated from biopsy specimens of periosteum, resuspended and cultured. The cell suspension was soaked in polymer fleeces. The cell-polymer constructs were transplanted by sinus lift 8 weeks after harvesting. The patients (n=35) had either one or both sides operated on. Seventeen had a one-stage sinus lift with simultaneous implantation (54 implants). In 18 patients the implants were inserted 3 months after augmentation (64 implants). Selected cases were biopsied. A control group (41 patients: one stage=48 implants, two stage=135 implants) had augmentation with autologous bone only. They were followed up clinically and radiologically for at least 24 months. Both implants and augmentation were significantly more successful in the control group. Failure of augmentation of the tissue-engineered bone was more common after large areas had been augmented. Eleven implants were lost in the study group and only one in the control group. Lifting the sinus floor with autologous bone is more reliable than with tissue-engineered transplants. Although lamellar bone can be found in periosteum-derived, tissue-engineered transplants, the range of indications must be limited.

  7. Fully automated, clinical-grade bone marrow processing: a single-centre experience

    Science.gov (United States)

    Mazzanti, Benedetta; Urbani, Serena; Dal Pozzo, Simone; Bufano, Paola; Ballerini, Lara; Gelli, Alessia; Sodi, Irene; Donnini, Irene; Di Gioia, Massimo; Guidi, Stefano; Camisani, Julien; Saccardi, Riccardo

    2017-01-01

    Background Clinical grade processing of harvested bone marrow is required in various clinical situations, particularly in the management of ABO mismatching in allogeneic haematopoietic stem cell transplantation (HSCT) and in regenerative medicine. Material and methods We report a single-centre experience using a fully automated, clinical grade, closed system (Sepax, Biosafe, Switzerland). From 2003 to 2015, 125 procedures were performed in our laboratory, including buffy-coat production for HSCT (n=58), regenerative medicine in an orthopaedic setting (n=54) and density-gradient separation in a trial for treatment of critical limb ischaemia (n=13). Results Buffy coat separation resulted in a median volume reduction of 85% (range, 75–87%), providing satisfactory red blood cell depletion (69%, range 30–88%) and a median recovery of CD34 cells of 96% (range, 81–134%) in the setting of allogeneic HSCT. Significantly greater volume reduction (90%; range, 90–92%) and red blood cell depletion (88%; range, 80–93%) were achieved by the new SmartRedux software released for Sepax2, validated in the last eight allogeneic HSCT. The density gradient separation programme resulted in complete red blood cell depletion associated with high CD34 recovery (69%; range, 36–124%). No reactions related to the quality of the product were reported. Time to engraftment following allogeneic HSCT was in the normal range. No cases of microbiological contamination related to the manipulation were reported. Discussion Clinical grade, automated bone marrow manipulation with Sepax was shown to be effective, giving operator-independent results and could be used for a broad range of clinical applications. PMID:27723450

  8. Bone densitometry

    DEFF Research Database (Denmark)

    Ravn, Pernille; Alexandersen, P; Møllgaard, A

    1999-01-01

    is much more expensive and technically complicated. By computerized iteration of single X-ray absorptiometry forearm scans we defined a region with 65% trabecular bone. The region was analyzed in randomized, double-masked, placebo- controlled trials: a 2-year trial with alendronate (n = 69), a 1-year...

  9. Allogeneic stem cell transplantation in a blast-phase chronic myeloid leukemia patient with carbapenem-resistant Klebsiella pneumoniae tricuspid valve endocarditis: A case report.

    Science.gov (United States)

    Kantarcioglu, Bulent; Bekoz, Huseyin Saffet; Olgun, Fatih Erkam; Cakal, Beytullah; Arkan, Burak; Turkoglu, Halil; Mert, Ali; Sargin, Deniz

    2016-10-01

    In chronic myeloid leukemia (CML), the occurrence of blastic transformation is rare. Treatment outcome is generally poor. Allogeneic stem cell transplantation (allo-SCT) is the only potentially curative treatment option for advanced-phase CML. Infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates are associated with high morbidity and mortality rates, particularly in patients with haematological malignancies. Infection and colonization by these multiresistant bacteria may represent a challenge in SCT recipients for the management of post-transplantation complications, as well as for the eligibility to receive a transplant in patients who acquire the pathogen prior to the procedure. We herein report the case of a blast-phase CML patient with a highly resistant, CRKP-associated tricuspid valve endocarditis, who was treated with a combination of systemic antimicrobial therapy and surgical valve repair, and subsequently underwent a successful allo-SCT.

  10. Comparison of autogeneic and allogeneic natural killer cells immunotherapy on the clinical outcome of recurrent breast cancer

    Directory of Open Access Journals (Sweden)

    Liang S

    2017-08-01

    Full Text Available Shuzhen Liang,1,2 Kecheng Xu,1,2 Lizhi Niu,1,2 Xiaohua Wang,1 Yingqing Liang,1 Mingjie Zhang,3 Jibing Chen,1,2 Mao Lin1,2 1Department of Central Laboratory, Fuda Cancer Hospital, Jinan University School of Medicine, Guangzhou, Guangdong, China; 2Fuda Cancer Institute, Guangzhou, Guangdong, China; 3Hank Bioengineering Co., Ltd, Shenzhen, China Abstract: In the present study, we aimed to compare the clinical outcome of autogeneic and allogeneic natural killer (NK cells immunotherapy for the treatment of recurrent breast cancer. Between July 2016 and February 2017, 36 patients who met the enrollment criteria were randomly assigned to two groups: autogeneic NK cells immunotherapy group (group I, n=18 and allogeneic NK cells immunotherapy group (group II, n=18. The clinical efficacy, quality of life, immune function, circulating tumor cell (CTC level, and other related indicators were evaluated. We found that allogeneic NK cells immunotherapy has better clinical efficacy than autogeneic therapy. Moreover, allogeneic NK cells therapy improves the quality of life, reduces the number of CTCs, reduces carcinoembryonic antigen and cancer antigen 15-3 (CA15-3 expression, and significantly enhances immune function. To our knowledge, this is the first clinical trial to compare the clinical outcome of autogeneic and allogeneic NK cells immunotherapy for recurrent breast cancer. Keywords: clinical outcome, autogeneic, allogeneic, natural killer cells, recurrent breast cancer

  11. Lack of cross-sensitization between α-1,3-galactosyltransferase knockout porcine and allogeneic skin grafts permits serial grafting.

    Science.gov (United States)

    Albritton, Alexander; Leonard, David A; Leto Barone, Angelo; Keegan, Josh; Mallard, Christopher; Sachs, David H; Kurtz, Josef M; Cetrulo, Curtis L

    2014-06-27

    The current standard of care for burns requiring operative treatment consists of early burn excision and autologous split-thickness skin grafting. However, in large burns, sufficient donor sites may not be available to achieve total coverage, necessitating temporary coverage with allogeneic human cadaver skin grafts or synthetic skin substitutes. A previous study from this laboratory demonstrated that skin grafts from alpha-1,3 galactosyltransferase knockout (GalT-KO) miniature swine enjoyed survival comparable to that of allogeneic skin grafts in baboons. In the present study, we have evaluated the immune response against sequential GalT-KO and allogeneic skin grafts to determine whether such serial grafts could extend the period of temporary wound coverage before definitive grafting with autologous skin. We report that rejection of primary GalT-KO skin grafts led to an anti-xenogeneic humoral response with no evidence for sensitization to alloantigens nor acceleration of rejection of allogeneic skin grafts. Similarly, presensitization with allogeneic skin did not lead to accelerated rejection of xenogeneic skin. These data suggest that GalT-KO skin grafts could provide an early first-line treatment in the management of severe burns that would not preclude subsequent use of allografts, and that serial grafting of GalT-KO skin and allogeneic skin could potentially be used to provide an extended period of temporary burn wound coverage.

  12. BMP2-loaded hollow hydroxyapatite microspheres exhibit enhanced osteoinduction and osteogenicity in large bone defects.

    Science.gov (United States)

    Xiong, Long; Zeng, Jianhua; Yao, Aihua; Tu, Qiquan; Li, Jingtang; Yan, Liang; Tang, Zhiming

    2015-01-01

    The regeneration of large bone defects is an osteoinductive, osteoconductive, and osteogenic process that often requires a bone graft for support. Limitations associated with naturally autogenic or allogenic bone grafts have demonstrated the need for synthetic substitutes. The present study investigates the feasibility of using novel hollow hydroxyapatite microspheres as an osteoconductive matrix and a carrier for controlled local delivery of bone morphogenetic protein 2 (BMP2), a potent osteogenic inducer of bone regeneration. Hollow hydroxyapatite microspheres (100±25 μm) with a core (60±18 μm) and a mesoporous shell (180±42 m(2)/g surface area) were prepared by a glass conversion technique and loaded with recombinant human BMP2 (1 μg/mg). There was a gentle burst release of BMP2 from microspheres into the surrounding phosphate-buffered saline in vitro within the initial 48 hours, and continued at a low rate for over 40 days. In comparison with hollow hydroxyapatite microspheres without BMP2 or soluble BMP2 without a carrier, BMP2-loaded hollow hydroxyapatite microspheres had a significantly enhanced capacity to reconstitute radial bone defects in rabbit, as shown by increased serum alkaline phosphatase; quick and complete new bone formation within 12 weeks; and great biomechanical flexural strength. These results indicate that BMP2-loaded hollow hydroxyapatite microspheres could be a potential new option for bone graft substitutes in bone regeneration.

  13. Osteoclasts prefer aged bone

    DEFF Research Database (Denmark)

    Henriksen, K; Leeming, Diana Julie; Byrjalsen, I

    2007-01-01

    We investigated whether the age of the bones endogenously exerts control over the bone resorption ability of the osteoclasts, and found that osteoclasts preferentially develop and resorb bone on aged bone. These findings indicate that the bone matrix itself plays a role in targeted remodeling...... of aged bones....

  14. Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion

    Science.gov (United States)

    Henry, David A; Carless, Paul A; Moxey, Annette J; O’Connell, Dianne; Stokes, Barrie J; Fergusson, Dean A; Ker, Katharine

    2014-01-01

    a non-significant increase in the risk of myocardial infarction (RR 1.11 95% CI 0.82, 1.50). Most of the data contributing to this added risk came from a single study - the BART trial (2008). Authors’ conclusions Anti-fibrinolytic drugs provide worthwhile reductions in blood loss and the receipt of allogeneic red cell transfusion. Aprotinin appears to be slightly more effective than the lysine analogues in reducing blood loss and the receipt of blood transfusion. However, head to head comparisons show a lower risk of death with lysine analogues when compared with aprotinin. The lysine analogues are effective in reducing blood loss during and after surgery, and appear to be free of serious adverse effects. PMID:21412876

  15. Cranial bone regeneration after cranioplasty using cryopreserved autogenous bone by a programmed freezer with a magnetic field in rats.

    Science.gov (United States)

    Kaku, Masato; Koseki, Hiroyuki; Kojima, Shunich; Sumi, Hiromi; Shikata, Hanaka; Kojima, Shotoku; Motokawa, Masahide; Fujita, Tadashi; Tanimoto, Kotaro; Tanne, Kazuo

    2014-01-01

    The purpose of this study was to develop a bone tissue bank using a programmed freezer with a magnetic field. Parietal bones were removed from rats and used for organ culture examination (non-cryopreserved, cryopreserved with a magnetic field (CAS) and cryopreserved without a magnetic field group). Next, other parietal bones were used for histological examination. The cryopreserved bones by a CAS freezer and dried bones were transplanted respectively. Control bones were replanted without cryopreservation. Animals were sacrificed at 4, 8, 12 and 24 weeks after surgery. After organ culture, the isolated osteoblasts from parietal bones which were cryopreserved by a CAS freezer can survive and proliferate as much as non-cryopreserved group. Histological examinations showed new bone formation in control and CAS group. These results suggest that bone tissue cryopreservation by CAS freezer can be successfully used for bone grafting which may be a novel option for regeneration medicine.

  16. Nonwoven scaffolds for bone regeneration

    OpenAIRE

    Durham, Elaine R.; Tronci, Giuseppe; Yang,Xuebin; Wood, David J.; Russell, Stephen J.

    2016-01-01

    Developing successful scaffolds requires clinicians to adopt a multidisciplinary approach in order to understand and stimulate the natural bone regeneration process. A variety of natural and synthetic biomaterials, including naturally extracted, chemically functionalised collagen and synthetic Poly(epsilon-caprolactone) (PCL), can be manufactured into fibres, enabling the formation of nonwoven scaffolds. Many different nonwoven architectures and structural features can then be introduced, dep...

  17. Amino acid-assisted synthesis of strontium hydroxyapatite bone ...

    Indian Academy of Sciences (India)

    present paper reports about the successful synthesis of stron- tium hydroxyapatite bone cement that could be widely used in orthopaedic applications to anchor implants to existing bone, reconstruct bone and deliver bioactive agents to the body by using glycine as template and freezing at 2. ◦. C. The main advantage of this ...

  18. Nutritional risk in allogeneic stem cell transplantation: rationale for a tailored nutritional pathway.

    Science.gov (United States)

    Aoyama, Takashi; Imataki, Osamu; Mori, Keita; Yoshitsugu, Kanako; Fukaya, Masafumi; Okamura, Ikue; Enami, Terukazu; Tatara, Raine; Ikeda, Takashi

    2017-04-01

    Hematopoietic stem cell transplantation carries nutrition-related risks. Therefore, nutritional therapy needs to be initiated before transplantation even takes place. We assessed nutritional risk among patients who underwent allogeneic stem cell transplantation. We assessed nutrient supply (calorie supply and protein supply) by chart review. Assessments were made from the pretreatment phase of transplantation to after the end of parenteral nutrition in 51 patients who underwent allogeneic stem cell transplantation at Shizuoka Cancer Center between 2007 and 2012. We compared nutrition-related adverse events and parameters between two groups: those in whom % loss of body weight was ≥7.5 and those in whom % loss of body weight was stem cell transplantation to ameliorate body weight loss associated with nutrition-related adverse events.

  19. No effect of bone morphogenetic protein-7 (OP-1) on the incorporation of impacted bone grafts in a realistic acetabular model.

    NARCIS (Netherlands)

    Buma, P.; Arts, J.J.C.; Gardeniers, J.W.M.; Verdonschot, N.J.J.; Schreurs, B.W.

    2008-01-01

    Bone morphogenetic proteins (BMPs) accelerate bone repair in experimental and clinical conditions. Impacted Morsellized Cancellous Bone grafts (MCB) are successfully used to reconstruct bone defects after failed hip implants. The main question in this study was if BMP-7 (OP-1) mixed with MCB could

  20. Allogeneic Stem Cells Alter Gene Expression and Improve Healing of Distal Limb Wounds in Horses

    OpenAIRE

    Textor, Jamie A.; Clark, Kaitlin C.; Walker, Naomi J.; Aristizobal, Fabio A.; Kol, Amir; LeJeune, Sarah S.; Bledsoe, Andrea; Davidyan, Arik; Gray, Sarah N.; Bohannon‐Worsley, Laurie K.; Woolard, Kevin D.; Borjesson, Dori L.

    2017-01-01

    Abstract Distal extremity wounds are a significant clinical problem in horses and humans and may benefit from mesenchymal stem cell (MSC) therapy. This study evaluated the effects of direct wound treatment with allogeneic stem cells, in terms of gross, histologic, and transcriptional features of healing. Three full‐thickness cutaneous wounds were created on each distal forelimb in six healthy horses, for a total of six wounds per horse. Umbilical cord‐blood derived equine MSCs were applied to...

  1. Activated allogeneic NK cells preferentially kill poor prognosis B-cell chronic lymphocytic leukemia cells

    Directory of Open Access Journals (Sweden)

    Diego Sanchez-Martinez

    2016-10-01

    Full Text Available Mutational status of TP53 together with expression of wild type (wt IGHV represents the most widely accepted biomarkers, establishing a very poor prognosis in B-cell chronic lymphocytic leukemia (B-CLL patients. Adoptive cell therapy using allogeneic HLA mismatched Natural Killer (NK cells has emerged as an effective and safe alternative in the treatment of acute myeloid and lymphoid leukemias that do not respond to traditional therapies. We have described that allogeneic activated NK cells eliminate hematological cancer cell lines with multidrug resistance acquired by mutations in the apoptotic machinery. This effect depends on the activation protocol, being B-lymphoblastoid cell lines (LCLs the most effective stimulus to activate NK cells. Here we have further analyzed the molecular determinants involved in allogeneic NK cell recognition and elimination of B-CLL cells, including the expression of ligands of the main NK cell activating receptors (NKG2D and NCRs and HLA mismatch. We present preliminary data suggesting that B-CLL susceptibility significantly correlates with HLA mismatch between NK cell donor and B-CLL patient. Moreover, we show that the sensitivity of B-CLL cells to NK cells depends on the prognosis based on TP53 and IGHV mutational status. Cells from patients with worse prognosis (mutated TP53 and wt IGHV are the most susceptible to activated NK cells. Hence, B-CLL prognosis may predict the efficacy of allogenic activated NK cells and, thus, NK cell transfer represents a good alternative to treat poor prognosis B-CLL patients who present a very short life expectancy due to lack of effective treatments.□

  2. Voriconazole-Induced Periostitis Mimicking Chronic Graft-versus-Host Disease after Allogeneic Stem Cell Transplantation.

    Science.gov (United States)

    Sweiss, Karen; Oh, Annie; Rondelli, Damiano; Patel, Pritesh

    2016-01-01

    Voriconazole is an established first-line agent for treatment of invasive fungal infections in patients undergoing allogeneic stem cell transplantation (ASCT). It is associated with the uncommon complication of periostitis. We report this complication in a 58-year-old female undergoing HSCT. She was treated with corticosteroids with minimal improvement. The symptoms related to periostitis can mimic chronic graft-versus-host disease in patients undergoing HSCT and clinicians should differentiate this from other diagnoses and promptly discontinue therapy.

  3. Informed consent: cultural and religious issues associated with the use of allogeneic and xenogeneic mesh products.

    Science.gov (United States)

    Jenkins, Eric D; Yip, Michael; Melman, Lora; Frisella, Margaret M; Matthews, Brent D

    2010-04-01

    Our aim was to investigate the views of major religions and cultural groups regarding the use of allogeneic and xenogeneic mesh for soft tissue repair. We contacted representatives from Judaism, Islam, Buddhism, Hinduism, Scientology, and Christianity (Baptists, Methodists, Seventh-Day Adventists, Catholics, Lutherans, Church of Jesus Christ of Latter-Day Saints, Evangelical, and Jehovah's Witnesses). We also contacted American Vegan and People for the Ethical Treatment of Animals (PETA). Standardized questionnaires were distributed to the religious and cultural authorities. Questions solicited views on the consumption of beef and pork products and the acceptability of human-, bovine-, or porcine-derived acellular grafts. Dietary restrictions among Jews and Muslims do not translate to tissue implantation restriction. Approximately 50% of Seventh-day Adventists and 40% of Buddhists practice vegetarianism, which may translate into a refusal of the use of xenogeneic tissue. Some Hindus categorically prohibit the use of human tissue and animal products; others allow the donation and receipt of human organs and tissues. PETA is opposed to all uses of animals, but not to human acellular grafts or organ transplantation. Some vegans prefer allogeneic to xenogeneic tissue. Allogeneic and xenogeneic acellular grafts are acceptable among Scientologists, Baptists, Lutherans, Evangelicals, and Catholics. Methodists, Jehovah's Witnesses, and The Church of Jesus Christ of Latter-Day Saints leave the decision up to the individual. Knowledge of religious and cultural preferences regarding biologic mesh assists the surgeon in obtaining a culturally sensitive informed consent for procedures involving acellular allogeneic or xenogeneic grafts. Copyright (c) 2010 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

  4. Delayed and short course of rapamycin prevents organ rejection after allogeneic liver transplantation in rats.

    Science.gov (United States)

    Hamdani, Salim; Thiolat, Allan; Naserian, Sina; Grondin, Cynthia; Moutereau, Stéphane; Hulin, Anne; Calderaro, Julien; Grimbert, Philippe; Cohen, José Laurent; Azoulay, Daniel; Pilon, Caroline

    2017-10-14

    To test whether a delayed and short course of rapamycin would induce immunosuppressive effects following allogeneic orthotopic liver transplantation (OLT) in rats. Allogeneic OLTs were performed using Dark Agouti livers transplanted into Lewis recipients, and syngeneic OLTs were performed using the Lewis rat strain. Rapamycin (1 mg/kg per day) was administered by gavage from day 4 to day 11 post-transplantation. Lymphocyte cellular compartments were analyzed by flow cytometry in draining lymph nodes, non-draining lymph nodes and the spleen at days 11 and 42 in rapamycin-treated rats, untreated control rats and syngeneic grafted rats. Skin grafts from Dark agouti or from F344 RT were performed at day 30 on liver grafted rats treated with rapamycin. An 8-d course of rapamycin treatment initiated 4 d following transplantation resulted in the survival of grafted rats for more than 100 d. In contrast, untreated rats died of liver failure within 13 to 21 d. The analysis of the cellular compartment revealed an increase in two cellular subpopulations, specifically myeloid-derived suppressor cells (MDSCs) and CD8+CD45RClow T cells, without major modifications in the regulatory T cell (Treg) compartment in treated rats in the early stages after grafting. We evaluated the ability of treated rats to reject third-party allogeneic skin grafts to confirm their immune competence. In contrast, when skin was collected from rats syngeneic to the grafted liver, it was not rejected. Our results demonstrate that short and delayed rapamycin treatment allows for tolerance in allogeneic OLT. The results also allowed for the identification of the mechanisms of tolerance induced by rapamycin by identifying MDSCs and CD8+CD45RClow T cells as associated with the state of tolerance.

  5. Suspected Pulmonary Infection with Trichoderma longibrachiatum after Allogeneic Stem Cell Transplantation

    OpenAIRE

    Akagi, Tomoaki; Kawamura, Chizuko; Terasawa, Norio; Yamaguchi, Kohei; Kubo, Kohmei

    2017-01-01

    Aspergillus and Candida species are the main causative agents of invasive fungal infections in immunocompromised human hosts. However, saprophytic fungi are now increasingly being recognized as serious pathogens. Trichoderma longibrachiatum has recently been described as an emerging pathogen in immunocompromised patients. We herein report a case of isolated suspected invasive pulmonary infection with T. longibrachiatum in a 29-year-old man with severe aplastic anemia who underwent allogeneic ...

  6. Bacterial bloodstream infections in the allogeneic hematopoietic cell transplant patient: new considerations for a persistent nemesis.

    Science.gov (United States)

    Dandoy, C E; Ardura, M I; Papanicolaou, G A; Auletta, J J

    2017-08-01

    Bacterial bloodstream infections (BSI) cause significant transplant-related morbidity and mortality following allogeneic hematopoietic cell transplantation (allo-HCT). This manuscript reviews the risk factors for and the bacterial pathogens causing BSIs in allo-HCT recipients in the contemporary transplant period. In addition, it offers insight into emerging resistant pathogens and reviews clinical management considerations to treat and strategies to prevent BSIs in allo-HCT patients.

  7. IMMUNE AND METABOLIC DISTURBANCES IN EXPERIMENTAL ACUTE TOXIC HEPATITIS: CORRECTION BY XENOGENIC AND ALLOGENIC HEPATOCYTES

    Directory of Open Access Journals (Sweden)

    A. I. Konoplya

    2016-01-01

    Full Text Available For correspondence: Konoplya Alexander Ivanovich. Address: 3,K. Marx St.,Kursk, 305041,Russian Federation. Tel.: job. (4712 58-81-76; mob. (910 317-87-88. E-mail: konoplya51@mail.ru.Aim. To study the corrective effects of allogeneic and xenogeneic hepatocytes on metabolic disturbances in acute liver toxicity.Material and methods. Investigations were carried out on 75 adult male Wistar rats weighing 120–160 g, 15 rats and 25 mice on the 5–6th days after birth. Acute toxic hepatitis (ATH was modeled by intramuscular injection of carbon tetrachloride at a dose of 3 ml / kg as a 50% solution in olive oil, five times at 24-hour intervals. Isolating xenogeneic (mouse and allogeneic hepatocytes was performed by method of Berry M.N., Friend D.S. The cell suspension was prepared daily and administered at a concentration of 2 × 106 /kg in recipients with ATH intraperitoneally, five times at 24-hour intervals, simultaneously with the first injection of hepatotropic poison.Results. Intoxication by carbon tetrachloride causes development of the biochemical syndromes of liver damage, activation of the functional metabolic activity of peripheral blood neutrophils and free-radical oxidation, breaks intraerythrocytic metabolism. The introduction of allogeneic hepatocytes in recipients with toxic hepatopathy is more efficiently compared with xenogeneic hepatocytes, it corrects local and systemic metabolic disturbances arising due to the impact of hepatotropic poison. Conclusion. Transplantation of xenogenic hepatocytes, and, to a greater extent, of allogenic hepatocytes in ATH conditions is an effective means to restore the functional metabolic activity of hepatocytes, neutrophils and erythrocytes. 

  8. Ocular Surface Rreconstruction with Allogeneic Limbal Stem Cell and Autologous Oral Mucosal Graft: Two Cases

    Directory of Open Access Journals (Sweden)

    Gözde Orman

    2013-04-01

    Full Text Available Two patients with severe ocular surface damage in both eyes are presented. In the patient with limbal stem cell deficiency, allogeneic limbal stem cell transplantation was performed. In the other patient with recurrent pterygium and symblepharon, autogenic oral mucosa transplantation was performed to manage the symblepharon. In this study, we discuss the methods that can be performed for reconstruction in patients with ocular surface disorder in both eyes. (Turk J Ophthalmol 2013; 43: 129-31

  9. Single-centre experience of allogeneic haemopoietic stem cell transplant in paediatric patients in Cape Town, South Africa

    Directory of Open Access Journals (Sweden)

    A van Eyssen

    2017-03-01

    Full Text Available Background. Allogeneic haemopoietic stem cell transplant (Allo-HSCT is a specialised and costly intervention, associated with significant morbidity and mortality. It is used to treat a broad range of paediatric conditions. South Africa (SA is an upper middle-income country with limitations on healthcare spending. The role of paediatric Allo-HSCT in this setting is reviewed. Objectives. To review paediatric patients who underwent Allo-HSCT at the Groote Schuur Hospital/University of Cape Town Private Academic Hospital transplant unit in Cape Town, South Africa, and received post-transplant care at Red Cross War Memorial Children’s Hospital, over the period January 2006 - December 2014 in respect of indications for the transplant, donor sources, conditioning regimens, treatment-related morbidity and overall survival (OS. Methods. A retrospective analysis of patient records was performed and a database was created in Microsoft Access. Descriptive analyses of relevant demographic, clinical and laboratory data were performed. Summary statistics of demographic and clinical parameters were derived with Excel. OS was calculated from the date of transplant to the date of an event (death or last follow-up using the Kaplan-Meier method in Statistica. Results. A total of 48 children received Allo-HSCT: 24 for haematological malignancies, 20 for non-oncological haematological conditions, 3 for immune disorders and 1 for adrenoleukodystrophy. There were 28 boys (median age 7.5 years and 20 girls (8.5 years. There were 31 sibling matched peripheral-blood stem cell (PBSC transplants and 1 maternal haploidentical PBSC transplant. Stem cells were mobilised from bone marrow into peripheral blood by administering granulocyte-colony stimulating factor to donors. PBSCs were harvested by apheresis. Eight patients received 10/10 HLA-matched grafts from unrelated donors. Six were PBSC grafts and 2 were bone marrow grafts. Three of the unrelated PBSC grafts were from

  10. Single-centre experience of allogeneic haemopoietic stem cell transplant in paediatric patients in Cape Town, South Africa.

    Science.gov (United States)

    Van Eyssen, A; Novitsky, N; De Wit, P; Schlaphoff, T; Thomas, V; Pillay, D; Hendricks, M; Davidson, A

    2017-02-27

    Allogeneic haemopoietic stem cell transplant (Allo-HSCT) is a specialised and costly intervention, associated with significant morbidity and mortality. It is used to treat a broad range of paediatric conditions. South Africa (SA) is an upper middle-income country with limitations on healthcare spending. The role of paediatric Allo-HSCT in this setting is reviewed. To review paediatric patients who underwent Allo-HSCT at the Groote Schuur Hospital/University of Cape Town Private Academic Hospital transplant unit in Cape Town, South Africa, and received post-transplant care at Red Cross War Memorial Children's Hospital, over the period January 2006 - December 2014 in respect of indications for the transplant, donor sources, conditioning regimens, treatment-related morbidity and overall survival (OS). A retrospective analysis of patient records was performed and a database was created in Microsoft Access. Descriptive analyses of relevant demographic, clinical and laboratory data were performed. Summary statistics of demographic and clinical parameters were derived with Excel. OS was calculated from the date of transplant to the date of an event (death) or last follow-up using the Kaplan-Meier method in Statistica. A total of 48 children received Allo-HSCT: 24 for haematological malignancies, 20 for non-oncological haematological conditions, 3 for immune disorders and 1 for adrenoleukodystrophy. There were 28 boys (median age 7.5 years) and 20 girls (8.5 years). There were 31 sibling matched peripheral-blood stem cell (PBSC) transplants and 1 maternal haploidentical PBSC transplant. Stem cells were mobilised from bone marrow into peripheral blood by administering granulocyte-colony stimulating factor to donors. PBSCs were harvested by apheresis. Eight patients received 10/10 HLA-matched grafts from unrelated donors. Six were PBSC grafts and 2 were bone marrow grafts. Three of the unrelated PBSC grafts were from SA donors. Eight transplants used umbilical cord blood

  11. Long-term outcome of allogeneic cultivated limbal epithelial transplantation for symblepharon caused by severe ocular burns.

    Science.gov (United States)

    Cheng, Jun; Zhai, Hualei; Wang, Junyi; Duan, Haoyun; Zhou, Qingjun

    2017-01-31

    The therapeutic effects of allogeneic cultivated limbal epithelial transplantation (CLET) for symblephara at different degrees caused by ocular burns were evaluated in this study. A series of interventional cases were involved in this retrospective study. Eighty eyes (80 patients) with symblephara underwent CLET and the success rates of surgical treatment as well as corneal conditions and risk factors for recurrent symblepharon were analyzed. The average age of patients was 32.4 ± 13.7 years (ranged from 4 to 60 years). The average follow-up time was 26.4 ± 13.6 months (ranged from 12 to 60 months). Symblepharon cases were caused by chemical burns (36 eyes) or thermal burns (44 eyes). The first surgical intervention achieved complete success in 40 eyes (50%), partial success in 25 eyes (31.3%), and failure in 15 eyes (18.8%). The rate of complete success was 85.0% in eyes with grade I/II symblephara, 51.5% in eyes with grade III eyes and 22.2% in eyes grade IV symblephara (P = 0.001). The treatment was completely successful in 23.1% of eyes with moderate or severe preoperative inflammatory action and 63.0% of eyes with mild or no inflammation (P = 0.000). The corneal conditions were improved in 43 eyes (53.8%), of which 21 eyes had improved visual acuity. The recurrence of symblepharon after the first CLET was positively correlated with symblepharon length (P = 0.003), preoperative inflammatory activity (P = 0.016) as well as postoperative cicatricial entropion and trichiasis (P = 0.038). CLET was effective on the recovery of anatomically deep fornixes in eyes caused by symblephara and corneal surface condition could be improved simultaneously. The success of surgical treatment was dependent on the effective control of inflammation and timely management of eyelid abnormalities.

  12. Effects of bone substitute architecture and surface properties on cell response, angiogenesis, and structure of new bone

    NARCIS (Netherlands)

    Bobbert, F.S.L.; Zadpoor, A.A.

    2017-01-01

    The success of bone substitutes used to repair bone defects such as critical sized defects depends on the architecture of the porous biomaterial. The architectural parameters and surface properties affect cell seeding efficiency, cell response, angiogenesis, and eventually bone formation. The

  13. Correlation and Agreement of Handheld Spirometry with Laboratory Spirometry in Allogeneic Hematopoietic Cell Transplant Recipients.

    Science.gov (United States)

    Cheng, Guang-Shing; Campbell, Angela P; Xie, Hu; Stednick, Zach; Callais, Cheryl; Leisenring, Wendy M; Englund, Janet A; Chien, Jason W; Boeckh, Michael

    2016-05-01

    Early detection of subclinical lung function decline may help identify allogeneic hematopoietic cell transplant (HCT) recipients who are at increased risk for late noninfectious pulmonary complications, including bronchiolitis obliterans syndrome. We evaluated the use of handheld spirometry in this population. Allogeneic HCT recipients enrolled in a single-center observational trial performed weekly spirometry with a handheld spirometer for 1 year after transplantation. Participants performed pulmonary function tests in an outpatient laboratory setting at 3 time points: before transplantation, at day 80 after transplantation, and at 1 year after transplantation. Correlation between the 2 methods was assessed by Pearson and Spearman correlations; agreement was assessed using Bland-Altman plots. A total of 437 subjects had evaluable pulmonary function tests. Correlation for forced expiratory volume in 1 second (FEV1) was r = .954 (P spirometry correlated well with laboratory spirometry after allogeneic HCT and may be useful for self-monitoring of patients for early identification of airflow obstruction. Copyright © 2016 American Society for Blood and Marrow Transplantation. All rights reserved.

  14. Fibrin glue therapy for severe hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Tirindelli, Maria Cristina; Flammia, Gerardo Paolo; Bove, Pierluigi; Cerretti, Raffaella; Cudillo, Laura; De Angelis, Gottardo; Picardi, Alessandra; Annibali, Ombretta; Nobile, Carolina; Cerchiara, Elisabetta; Dentamaro, Teresa; De Fabritiis, Paolo; Lanti, Alessandro; Ferraro, Angelo Salvatore; Sergi, Federico; Di Piazza, Fabio; Avvisati, Giuseppe; Arcese, William

    2014-10-01

    Hemorrhagic cystitis (HC) occurring after allogeneic transplantation significantly affects quality of life and, in some cases, becomes intractable, increasing the risk of death. To date, its therapy is not established. We used the hemostatic agent fibrin glue (FG) to treat 35 patients with refractory post-transplantation HC. Of 322 adult patients undergoing an allogeneic transplantation for hematological malignancy, 35 developed grade ≥ 2 HC refractory to conventional therapy and were treated with FG, diffusely sprayed on bleeding mucosa by an endoscopic applicator. The cumulative incidence of pain discontinuation and complete remission, defined as regression of all symptoms and absence of hematuria, was 100% at 7 days and 83% ± 7%, respectively, at 50 days from FG application. The 6-month probability of overall survival for all 35 patients and for the 29 in complete remission was 49% ± 8% and 59% ± 9%, respectively. In the matched-pair analysis, the 5-year probability of overall survival for the 35 patients with HC and treated with FG was not statistically different from that of the comparative cohort of 35 patients who did not develop HC (32% ± 9% versus 37% ± 11%, P = not significant). FG therapy is a feasible, effective, repeatable, and affordable procedure for treating grade ≥2 HC after allogeneic transplantation. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  15. Allogeneic mesenchymal precursor cell therapy to limit remodeling after myocardial infarction: the effect of cell dosage.

    Science.gov (United States)

    Hamamoto, Hirotsugu; Gorman, Joseph H; Ryan, Liam P; Hinmon, Robin; Martens, Timothy P; Schuster, Michael D; Plappert, Theodore; Kiupel, Matti; St John-Sutton, Martin G; Itescu, Silviu; Gorman, Robert C

    2009-03-01

    This experiment assessed the dose-dependent effect of a unique allogeneic STRO-3-positive mesenchymal precursor cell (MPC) on postinfarction left ventricular (LV) remodeling. The MPCs were administered in a manner that would simulate an off-the-self, early postinfarction, preventative approach to cardiac cell therapy in a sheep transmural myocardial infarct (MI) model. Allogeneic MPCs were isolated from male crossbred sheep. Forty-six female sheep underwent coronary ligation to produce a transmural LV anteroapical infarction. One hour after infarction, the borderzone myocardium received an injection of 25, 75, 225, or 450 x 10(6) MPCs, or cell medium. Echocardiography was performed at 4 and 8 weeks after MI to quantify LV end-diastolic (LVEDV) and end-systolic volumes (LVESV), ejection fraction (EF), and infarct expansion. CD31 and smooth muscle actin (SMA) immunohistochemical staining was performed on infarct and borderzone specimens to quantify vascular density. Compared with controls, low-dose (25 and 75 x 10(6) cells) MPC treatment significantly attenuated infarct expansion and increases in LVEDV and LVESV. EF was improved at all cell doses. CD31 and SMA immunohistochemical staining demonstrated increased vascular density in the borderzone only at the lower cell doses. There was no evidence of myocardial regeneration within the infarct. Allogeneic STRO-3 positive MPCs attenuate the remodeling response to transmural MI in a clinically relevant large-animal model. This effect is associated with vasculogenesis and arteriogenesis within the borderzone and infarct and is most pronounced at lower cell doses.

  16. Root and periodontal tissue development after allogenic tooth transplantation between rat littermates.

    Science.gov (United States)

    Andou, K; Nakamura, M; Ina, Y; Sasaki, K; Sasano, Y

    2011-05-01

    The study was designed to investigate the development of roots and periodontal tissues after allogenic tooth transplantation between rat littermates by micro-computed tomography (micro-CT) and histology. The upper right second molars in 2-week-old rats were extracted and immediately transplanted into the upper right first molar socket of rat littermates under anesthesia. The upper left second molars in 2-week-old recipient rats were used as a control. The rats were fixed and tissues analyzed at 0, 4, 8, or 12 weeks after transplantation. Root development of seven rats in each group was analyzed quantitatively using micro-CT. Periodontal tissue formation was examined qualitatively by histologic methods. Roots developed after allogenic transplantation, but they were significantly shorter than control roots. The number of roots varied from one to four in transplanted teeth, while it was consistently four in control teeth. Periodontal tissue formation in transplanted teeth was equivalent to that of the control teeth. Allogenic transplantation between rat littermates permits root development and periodontal tissue formation. © 2010 John Wiley & Sons A/S.

  17. Current status of allogeneic transplantation for aggressive non-Hodgkin lymphoma.

    Science.gov (United States)

    van Besien, Koen

    2011-11-01

    To provide a succinct update on the role of allogeneic stem cell transplantation (allo-SCT) in the management of patients with aggressive lymphomas. To clarify the indications for allogeneic transplantation vis-à-vis autologous transplant and to discuss the rationale and potential benefits of reduced intensity conditioning (RIC), nonmyeloablative (NMA) transplant, T-cell depletion and variations in graft vs. host disease (GVHD) prophylaxis. Considerable effort has been spent in developing transplant regimens with reduced toxicity and reduced GVHD. The role of allogeneic transplantation has also been redefined in light of advances in lymphoma classification, diagnostic methods, particularly PET scan and advances in transplant technology. Haplo and umbilical cord blood SCT allow identification of a donor for nearly all patients. In diffuse large B-cell lymphoma, the outcome of allo-SCT depends on patient characteristics and chemosensitivity. It is useful after failure of auto-SCT and in partial responses to salvage therapy. Allo-SCT may be the treatment of choice for advanced T-cell and natural killer cell lymphoma and for adult T-cell leukemia-lymphoma. Prophylactic or preemptive donor lymphocyte infusion may be useful, but requires controlled studies. RIC and NMA conditioning have reduced early toxicity but are associated with increased risk for disease recurrence. Promising data have been reported from a novel conditioning regimen combining NMA with ibritumomab tiuxetan. T-cell depletion reduces chronic GVHD but has some increase in rate of recurrence. Rapamycin may be associated with reduction in risk for disease recurrence.

  18. Risk Factors and Outcomes of Invasive Fungal Infections in Allogeneic Hematopoietic Cell Transplant Recipients.

    Science.gov (United States)

    Miceli, Marisa H; Churay, Tracey; Braun, Thomas; Kauffman, Carol A; Couriel, Daniel R

    2017-06-01

    Allogeneic hematopoietic cell transplant (HCT) recipients are at increased risk of invasive fungal infections (IFI), which are associated with a high mortality rate. We evaluated the impact of IFI in allogeneic HCT patients. In total, 541 consecutive allogeneic HCT recipients were included. The cumulative incidence of any IFI and mold infections at 1-year post-HCT was 10 and 7%, respectively. Median times to IFI and mold infection were 200 and 210 days, respectively. There was a trend toward fewer IFI and mold infections in the last several years. Both acute graft-versus-host disease (GVHD) (OR 1.83, p = 0.05) and corticosteroid duration (OR 1.0, p = 0.026) were significantly associated with increased risk of IFI, acute GVHD (OR 2.3, p = 0.027) emerged as the most important association with mold infections. Any IFI [HR 4.1 (2.79-6.07), p 90 days was also significantly associated with higher NRM [HR 1.9 (1.3-2.6), p < 0.0001]. This study highlights the impact of IFI on NRM among HCT patients. The decrease in number of IFI and mold infections over the last several years may reflect the benefit of prophylaxis with mold-active antifungal agents.

  19. Nutritional status of allogeneic hematopoietic stem cell transplantation recipients: influencing risk factors and impact on survival.

    Science.gov (United States)

    El-Ghammaz, Amro Mohamed Sedky; Ben Matoug, Rima; Elzimaity, Maha; Mostafa, Nevine

    2017-04-24

    Patients subjected to allogeneic hematopoietic stem cell transplantation (HSCT) are at increased nutritional risk which in turn may alter their outcome. For providing good nutritional care for patients, it is important to analyze risk factors influencing nutritional status during and after HSCT. Fifty patients undergoing allogeneic HSCT were subjected to nutritional status assessment by using the patient-generated subjective global assessment (PG-SGA) at initial admission, day 30 and day 180. Two patients (4%) had malnutrition at admission, 36 (72%) at day 30, and 24 (48%) at day 180. At day 30, comorbidity index higher than 0 and fever lasting for more than 1 week had a significant impact on nutritional status (P = .004 and P = .006, respectively). Regarding day 180, comorbidity index higher than 0 and presence of ≥grade II acute gastrointestinal graft versus host disease (GI GVHD) significantly influenced nutritional status (P = .017 and P = .026, respectively). Well-nourished patients at admission and day 180 had a significantly higher overall survival (OS) in comparison to malnourished patients (P Nutritional status at admission and day 180 had a significant influence on OS in multivariate analysis (P = .039 and P = .032, respectively). Allogeneic HSCT patients having high comorbidity index, developing prolonged fever, and experiencing ≥grade II acute GI GVHD suffer from worsening in their nutritional status during hospitalization and after discharge. Also, nutritional status at admission and day 180 significantly influences their survival.

  20. Radiation sterilized bone response to dynamic loading

    Energy Technology Data Exchange (ETDEWEB)

    Mardas, Marcin, E-mail: marcin.mardas@skpp.edu.pl [Department of Oncology, Poznan University of Medical Sciences, ul. Szamarzewskiego 82/84, 60-569 Poznan (Poland); Kubisz, Leszek [Department of Biophysics, Poznan University of Medical Sciences, ul. Fredry 10, 61-701 Poznan (Poland); Biskupski, Piotr; Mielcarek, Slawomir [Department of Physics, Adam Mickiewicz University, ul. Umultowska 85, 61-614 Poznan (Poland); Stelmach-Mardas, Marta [Department of Bromatology, Poznan University of Medical Sciences, ul. Marcelinska 420, 60-354 Poznan (Poland); Kaluska, Iwona [Centre for Radiation Research and Technology, Institute of Nuclear Chemistry and Technology, ul. Dorodna 16, 03-195 Warsaw (Poland)

    2012-08-01

    Allogeneic bone grafts are used on a large scale in surgeries. To avoid the risk of infectious diseases, allografts should be radiation-sterilized. So far, no international consensus has been achieved regarding the optimal radiation dose. Many authors suggest that bone sterilization deteriorates bone mechanical properties. However, no data on the influence of ionizing radiation on bone dynamic mechanical properties are available. Bovine femurs from 2-year old animal were machine cut and irradiated with the doses 10, 15, 25, 35, 45 and 50 kGy. Dynamic mechanical analysis was performed at 1-10 Hz at the temperature range of 0-350 Degree-Sign C in 3-point bending configuration. No statistically significant differences in storage modulus were observed. However, there were significant decreased values of loss modulus between the samples irradiated with doses of 10 ({down_arrow}14.3%), 15, 45 and 50 kGy ({down_arrow}33.2%) and controls. It was stated that increased irradiation dose decreases the temperature where collagen denaturation process starts and increases the temperature where the collagen denaturation process finishes. It was shown that activation energy of denaturation process is significantly higher for the samples irradiated with the dose of 50 kGy (615 kJ/mol) in comparison with control samples and irradiation with other doses (100-135 kJ/mol). - Highlights: Black-Right-Pointing-Pointer We examine changes in the storage modulus and loss modulus of samples irradiated with doses of 10-50 kGy. Black-Right-Pointing-Pointer We examine changes in the denaturation temperature of samples irradiated with doses of 10-50 kGy. Black-Right-Pointing-Pointer We examine changes in the activation energy of denaturation process of samples irradiated with doses of 10-50 kGy.

  1. The utility of bone scans in rheumatology

    Energy Technology Data Exchange (ETDEWEB)

    Duncan, I.; Dorai-Raj, A.; Khoo, K.; Tymans, K.; Brook, A. [The Canberra Hospital, Canberra, ACT, (Australia)

    1997-09-01

    Full text: Introduction: Bone scans are the commonest diagnostic imaging services requested by Australian rheumatologists. Medicare figures suggest that an average rheumatologist orders about $50 000 (AUS) of bone scans annually. Aims: To ascertain the reasons why rheumatologists request bone scans and how it affects their patient management. Methods: A two-part prospective survey was administered before and after every bone scan ordered by four rheumatologists over a six-month period in 1996. Results: A total of 136 bone scans were requested (66.2% whole body; 33.8% regional; 6% SPECT). The primary indications for scanning were (1) to confirm a clinical diagnosis (38%); (2) to exclude a diagnosis (34%); (3) to localize site of pain (17%); and (4) to assist in management (6%). The common diseases that rheumatologists were attempting to confirm/exclude with bone scanning were inflammatory arthritis, malignancy, and fracture. However, the commonest provisional and final diagnosis was soft tissue rheumatism (18%) followed by inflammatory arthritis (15%) and osteoarthritis (11%). In 24% of patients with a provisional diagnosis of soft tissue rheumatism the diagnosis was changed by the bone scan. The scan was successful in excluding a diagnosis in 88 per cent where this was the primary indication for the test. It was successful in confirming a diagnosis in 79 per cent where this was the primary indication. In 32 per cent the bone scan altered the clinical diagnosis and in 43 per cent it altered management. The bone scan result prevented further investigations in 60 per cent. Conclusions: The commonest pre-scan and post-scan diagnosis is soft tissue rheumatism. Rheumatologists predominantly request bone scanning to confirm or exclude their clinical suspicion of inflammatory arthritis, malignancy, and fracture. Bone scans were successful in achieving these objectives in at least 79 per cent of cases.

  2. Bone Marrow Transplantation for Recessive Dystrophic Epidermolysis Bullosa

    Science.gov (United States)

    Wagner, John E.; Ishida-Yamamoto, Akemi; McGrath, John A.; Hordinsky, Maria; Keene, Douglas R.; Riddle, Megan J.; Osborn, Mark J.; Lund, Troy; Dolan, Michelle; Blazar, Bruce R.; Tolar, Jakub

    2010-01-01

    Background Recessive dystrophic epidermolysis bullosa is an incurable, often fatal mucocutaneous blistering disease caused by mutations in COL7A1, the gene encoding type VII collagen (C7). On the basis of preclinical data showing biochemical correction and prolonged survival in col7−/− mice, we hypothesized that allogeneic marrow contains stem cells capable of ameliorating the manifestations of recessive dystrophic epidermolysis bullosa in humans. Methods Between October 2007 and August 2009, we treated seven children who had recessive dystrophic epidermolysis bullosa with immunomyeloablative chemotherapy and allogeneic stem-cell transplantation. We assessed C7 expression by means of immunofluorescence staining and used transmission electron microscopy to visualize anchoring fibrils. We measured chimerism by means of competitive polymerase-chain-reaction assay, and documented blister formation and wound healing with the use of digital photography. Results One patient died of cardiomyopathy before transplantation. Of the remaining six patients, one had severe regimen-related cutaneous toxicity, with all having improved wound healing and a reduction in blister formation between 30 and 130 days after transplantation. We observed increased C7 deposition at the dermal–epidermal junction in five of the six recipients, albeit without normalization of anchoring fibrils. Five recipients were alive 130 to 799 days after transplantation; one died at 183 days as a consequence of graft rejection and infection. The six recipients had substantial proportions of donor cells in the skin, and none had detectable anti-C7 antibodies. Conclusions Increased C7 deposition and a sustained presence of donor cells were found in the skin of children with recessive dystrophic epidermolysis bullosa after allogeneic bone marrow transplantation. Further studies are needed to assess the long-term risks and benefits of such therapy in patients with this disorder. (Funded by the National

  3. Arresting rampant dental caries with silver diamine fluoride in a young teenager suffering from chronic oral graft versus host disease post-bone marrow transplantation: a case report

    Science.gov (United States)

    2014-01-01

    Background Rampant caries is an advanced and severe dental disease that affects multiple teeth. This case describes the management of rampant caries in a young teenager suffering from chronic oral graft versus host disease after allogeneic bone marrow transplantation. Case presentation A 14-year-old Chinese boy suffering from β–thalassemia major was referred to the dental clinic for the management of rampant dental caries. An oral examination revealed pale conjunctiva, bruising of lips, and depapillation of tongue indicating an underlying condition of anemia. The poor oral condition due to topical and systemic immunosuppressants was seriously aggravated, and rampant caries developed rapidly, affecting all newly erupted, permanent teeth. The teeth were hypersensitive and halitosis was apparent. Strategies for oral health education and diet modification were given to the patient. Xylitol chewing gum was used to stimulate saliva flow to promote remineralization of teeth. Silver diamine fluoride was topically applied to arrest rampant caries and to relieve pain from hypersensitivity. Carious teeth with pulpal involvement were endodontically treated. Stainless steel crowns were provided on molars to restore chewing function, and polycarbonate crowns were placed on premolars, upper canines and incisors. Conclusion This case report demonstrates success in treating a young teenager with severe rampant dental decay by contemporary caries control and preventive strategy. PMID:24383434

  4. Arresting rampant dental caries with silver diamine fluoride in a young teenager suffering from chronic oral graft versus host disease post-bone marrow transplantation: a case report.

    Science.gov (United States)

    Chu, Chun-Hung; Lee, Angeline Hui-Cheng; Zheng, Liwu; Mei, May Lei; Chan, Godfrey Chi-Fung

    2014-01-03

    Rampant caries is an advanced and severe dental disease that affects multiple teeth. This case describes the management of rampant caries in a young teenager suffering from chronic oral graft versus host disease after allogeneic bone marrow transplantation. A 14-year-old Chinese boy suffering from β-thalassemia major was referred to the dental clinic for the management of rampant dental caries. An oral examination revealed pale conjunctiva, bruising of lips, and depapillation of tongue indicating an underlying condition of anemia. The poor oral condition due to topical and systemic immunosuppressants was seriously aggravated, and rampant caries developed rapidly, affecting all newly erupted, permanent teeth. The teeth were hypersensitive and halitosis was apparent. Strategies for oral health education and diet modification were given to the patient. Xylitol chewing gum was used to stimulate saliva flow to promote remineralization of teeth. Silver diamine fluoride was topically applied to arrest rampant caries and to relieve pain from hypersensitivity. Carious teeth with pulpal involvement were endodontically treated. Stainless steel crowns were provided on molars to restore chewing function, and polycarbonate crowns were placed on premolars, upper canines and incisors. This case report demonstrates success in treating a young teenager with severe rampant dental decay by contemporary caries control and preventive strategy.

  5. Use of engineered bone for sinus augmentation.

    Science.gov (United States)

    Beaumont, Christian; Schmidt, Roswitha J; Tatakis, Dimitris N; Zafiropoulos, Gregory-George

    2008-03-01

    Tissue-engineered bone grafts represent an appealing alternative for maxillary sinus augmentation because they eliminate the significant drawbacks associated with extra- and intraoral bone-harvesting procedures. In the present case series, we document the outcomes of sinus augmentation surgery using tissue-engineered bone grafts. Three patients requiring bilateral sinus augmentation received tissue-engineered bone grafts combined with xenograft prior to implant placement. Implants were placed and loaded 6 and 12 months postaugmentation, respectively. Radiographs were taken and clinical examinations were performed preoperatively and at 4, 6, 12, and 18 months postaugmentation. Biopsies were obtained at 4 and 6 months postaugmentation. Standardized orthopantomograms were used to measure the posterior maxilla bone height. None of the patients experienced untoward complications during or following the therapeutic procedures. Ten implants were inserted into the augmented sinuses and loaded. Biopsies revealed a lack of inflammation or pathology; newly formed fibrous bone with osteoblastic activity and xenograft particles was evident. Compared to 4 months postaugmentation, augmented tissue was more mature at 6 months. The postoperative (18 months) bone height in augmented areas was significantly greater than the preoperative height (P bone height. Sinus augmentation using tissue-engineered bone grafts was successful in all three cases, permitting the subsequent insertion and loading of dental implants. The present cases demonstrated the feasibility of using engineered bone for sinus augmentation. Controlled clinical trials will be required to evaluate this new and evolving treatment modality.

  6. Optimizing Bone Health in Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Jason L. Buckner

    2015-01-01

    Full Text Available Duchenne muscular dystrophy (DMD is an X-linked recessive disorder characterized by progressive muscle weakness, with eventual loss of ambulation and premature death. The approved therapy with corticosteroids improves muscle strength, prolongs ambulation, and maintains pulmonary function. However, the osteoporotic impact of chronic corticosteroid use further impairs the underlying reduced bone mass seen in DMD, leading to increased fragility fractures of long bones and vertebrae. These serious sequelae adversely affect quality of life and can impact survival. The current clinical issues relating to bone health and bone health screening methods in DMD are presented in this review. Diagnostic studies, including biochemical markers of bone turnover and bone mineral density by dual energy X-ray absorptiometry (DXA, as well as spinal imaging using densitometric lateral spinal imaging, and treatment to optimize bone health in patients with DMD are discussed. Treatment with bisphosphonates offers a method to increase bone mass in these children; oral and intravenous bisphosphonates have been used successfully although treatment is typically reserved for children with fractures and/or bone pain with low bone mass by DXA.

  7. Allogeneic hematopoietic stem cell transplantation allows long-term complete remission and curability in high-risk Waldenström’s macroglobulinemia. Results of a retrospective analysis of the Société Française de Greffe de Moelle et de Thérapie Cellulaire

    Science.gov (United States)

    Garnier, Alice; Robin, Marie; Larosa, Fabrice; Golmard, Jean-Louis; Le Gouill, Steven; Coiteux, Valérie; Tabrizi, Reza; Bulabois, Claude-Eric; Cacheux, Victoria; Kuentz, Mathieu; Dreyfus, Brigitte; Dreger, Peter; Rio, Bernard; Moles-Moreau, Marie-Pierre; Bilger, Karin; Bay, Jacques-Olivier; Leblond, Véronique; Blaise, Didier; Tournilhac, Olivier; Dhédin, Nathalie

    2010-01-01

    Background Patients with poor-risk Waldenström’s macroglobulinemia have suboptimal response and early post-treatment relapse with conventional therapies. Hence, new therapeutic approaches such as allogeneic stem cell transplantation should be evaluated in these patients. Design and Methods We examined the long-term outcome of allogeneic stem cell transplantation in Waldenström’s macroglobulinemia by studying the records of 24 patients reported in the SFGM-TC database and one transplanted in the bone marrow unit in Hamburg. Results Median age at the time of transplant was 48 years (range, 24–64). The patients had previously received a median of 3 lines of therapy (range, 1–6) and 44% of them had refractory disease at time of transplant. Allogeneic stem cell transplantation after myeloablative (n=12) or reduced-intensity (n=13) conditioning yielded an overall response rate of 92% and immunofixation-negative complete remission in 50% of evaluable patients. With a median follow-up of 64 months among survivors (range, 11–149 months), 5-year overall survival and progression-free survival rates were respectively, 67% (95% CI: 46–81) and 58% (95% CI: 38–75). The 5-year estimated risk of progression was 25% (95% CI: 10–36%), with only one relapse among the 12 patients who entered complete remission, versus 5 in the 12 patients who did not. Only one of the 6 relapses occurred more than three years post-transplant. Conclusions Allogeneic stem cell transplantation yields a high rate of complete remissions and is potentially curative in poor-risk Waldenström’s macroglobulinemia. PMID:20081058

  8. Systemic Delivery of Bone Marrow Mesenchymal Stem Cells for In Situ Intervertebral Disc Regeneration

    Science.gov (United States)

    Almeida, Catarina R.; Almeida, Maria Inês; Silva, Andreia M.; Molinos, Maria; Lamas, Sofia; Pereira, Catarina L.; Teixeira, Graciosa Q.; Monteiro, António T.; Santos, Susana G.; Gonçalves, Raquel M.; Barbosa, Mário A.

    2016-01-01

    Abstract Cell therapies for intervertebral disc (IVD) regeneration presently rely on transplantation of IVD cells or stem cells directly to the lesion site. Still, the harsh IVD environment, with low irrigation and high mechanical stress, challenges cell administration and survival. In this study, we addressed systemic transplantation of allogeneic bone marrow mesenchymal stem cells (MSCs) intravenously into a rat IVD lesion model, exploring tissue regeneration via cell signaling to the lesion site. MSC transplantation was performed 24 hours after injury, in parallel with dermal fibroblasts as a control; 2 weeks after transplantation, animals were killed. Disc height index and histological grading score indicated less degeneration for the MSC‐transplanted group, with no significant changes in extracellular matrix composition. Remarkably, MSC transplantation resulted in local downregulation of the hypoxia responsive GLUT‐1 and in significantly less herniation, with higher amounts of Pax5+ B lymphocytes and no alterations in CD68+ macrophages within the hernia. The systemic immune response was analyzed in the blood, draining lymph nodes, and spleen by flow cytometry and in the plasma by cytokine array. Results suggest an immunoregulatory effect in the MSC‐transplanted animals compared with control groups, with an increase in MHC class II+ and CD4+ cells, and also upregulation of the cytokines IL‐2, IL‐4, IL‐6, and IL‐10, and downregulation of the cytokines IL‐13 and TNF‐α. Overall, our results indicate a beneficial effect of systemically transplanted MSCs on in situ IVD regeneration and highlight the complex interplay between stromal cells and cells of the immune system in achieving successful tissue regeneration. Stem Cells Translational Medicine 2017;6:1029–1039 PMID:28297581

  9. Arresting rampant dental caries with silver diamine fluoride in a young teenager suffering from chronic oral graft versus host disease post-bone marrow transplantation: a case report

    OpenAIRE

    Chan, GCF; Lee, AHC; Zheng, L; Chu, CH; Mei, L

    2014-01-01

    BACKGROUND: Rampant caries is an advanced and severe dental disease that affects multiple teeth. This case describes the management of rampant caries in a young teenager suffering from chronic oral graft versus host disease after allogeneic bone marrow transplantation. CASE PRESENTATION: A 14-year-old Chinese boy suffering from beta-thalassemia major was referred to the dental clinic for the management of rampant dental caries. An oral examination revealed pale conjunctiva, bruising of lips, ...

  10. Current Graft-versus-Host Disease-Free, Relapse-Free Survival: A Dynamic Endpoint to Better Define Efficacy after Allogenic Transplant.

    Science.gov (United States)

    Solomon, Scott R; Sizemore, Connie; Zhang, Xu; Ridgeway, Michelle; Solh, Melhem; Morris, Lawrence E; Holland, H Kent; Bashey, Asad

    2017-07-01

    An accurate measure of allogeneic transplant efficacy should take into account quality-of-life issues associated with graft-versus-host disease (GVHD). However, unlike death and relapse, GVHD morbidity is temporary in many patients, and this fact must be reflected in such an outcome measure. Therefore, we have defined a new composite endpoint, called current GVHD-free, relapse-free survival (CGRFS), which is the probability, at any time post-transplant, of being alive, in remission, and without clinically significant chronic GVHD, defined as moderate-severe by the National Institutes of Health consensus criteria. Chronic GVHD is considered a dynamic event, which can resolve once manifestations are quiescent and systemic immunosuppression discontinued. CGRFS is achieved through linear combination of relevant Kaplan-Meier estimates. We evaluated 422 consecutive patients receiving an allogeneic transplant at a single institution between January 2010 and July 2015. With a median follow-up of 36 months, estimated 3-year overall and disease-free survival was 60% and 54%, respectively. Conventionally defined GRFS at 1, 2, 3, and 4 years was 33%, 26%, 23%, and 22%, respectively. In contrast, the corresponding rates of CGRFS were 45%, 46%, 47%, and 49%, respectively. Patients living with active moderate-severe chronic GVHD decreased over time, quantitated at 23%, 14%, 7%, and 4%, respectively, at 1, 2, 3, and 4 years post-transplant. Whereas only approximately one-fourth of patients achieve transplant success as defined by conventional GRFS, nearly half of patients, by CGRFS, are considered cured without the morbidity of ongoing GVHD. We propose that CGRFS may represent a more dynamic and accurate estimate of long-term transplant effectiveness. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  11. Teratocarcinomas Arising from Allogeneic Induced Pluripotent Stem Cell-Derived Cardiac Tissue Constructs Provoked Host Immune Rejection in Mice.

    Science.gov (United States)

    Kawamura, Ai; Miyagawa, Shigeru; Fukushima, Satsuki; Kawamura, Takuji; Kashiyama, Noriyuki; Ito, Emiko; Watabe, Tadashi; Masuda, Shigeo; Toda, Koichi; Hatazawa, Jun; Morii, Eiichi; Sawa, Yoshiki

    2016-01-14

    Transplantation of induced pluripotent stem cell-derived cardiac tissue constructs is a promising regenerative treatment for cardiac failure: however, its tumourigenic potential is concerning. We hypothesised that the tumourigenic potential may be eliminated by the host immune response after allogeneic cell transplantation. Scaffold-free iPSC-derived cardaic tissue sheets of C57BL/6 mouse origin were transplanted into the cardiac surface of syngeneic C57BL/6 mice and allogeneic BALB/c mice with or without tacrolimus injection. Syngeneic mice and tacrolimus-injected immunosuppressed allogeneic mice formed teratocarcinomas with identical phenotypes, characteristic, and time courses, as assessed by imaging tools including (18)F-fluorodeoxyglucose-positron emission tomography. In contrast, temporarily immunosuppressed allogeneic mice, following cessation of tacrolimus injection displayed diminished progression of the teratocarcinoma, accompanied by an accumulation of CD4/CD8-positive T cells, and finally achieved complete elimination of the teratocarcinoma. Our results indicated that malignant teratocarcinomas arising from induced pluripotent stem cell-derived cardiac tissue constructs provoked T cell-related host immune rejection to arrest tumour growth in murine allogeneic transplantation models.

  12. Evaluation of the immune status against measles, mumps, and rubella in adult allogeneic hematopoietic stem cell transplantation recipients.

    Science.gov (United States)

    Kawamura, Koji; Yamazaki, Rie; Akahoshi, Yu; Nakano, Hirofumi; Ugai, Tomotaka; Wada, Hidenori; Yamasaki, Ryoko; Ishihara, Yuko; Sakamoto, Kana; Ashizawa, Masahiro; Sato, Miki; Terasako-Saito, Kiriko; Kimura, Shun-ichi; Kikuchi, Misato; Nakasone, Hideki; Kanda, Junya; Kako, Shinichi; Tanihara, Aki; Nishida, Junji; Kanda, Yoshinobu

    2015-03-01

    Previous studies have shown that most patients lose immunity to measles, mumps, and rubella (MMR) during long-term follow-up after allogeneic hematopoietic stem cell transplantation (HSCT), and immunizations against them have been investigated. However, these previous studies mainly targeted pediatric patients and information in adult patients is still insufficient. We evaluated the immunity to MMR in 45 adult allogeneic HSCT patients. None of these patients received vaccination after HSCT. The seropositive rates at six years after allogeneic HSCT were estimated to be less than 44% for measles, less than 10% for mumps, and less than 36% for rubella. Thirteen of the 16 female patients who were 16-39 years old were negative or equivocal for rubella. Patients who developed grade II-IV acute graft-versus-host disease tended to become seronegative for measles and rubella at two years after HSCT, although the difference was not statistically significant. This study showed that most adult patients lost immunity to MMR after allogeneic HSCT. Although we did not evaluate the safety and efficacy of vaccination in this study, most HSCT guidelines recommend vaccination for HSCT recipients without active chronic graft-versus-host disease or ongoing immunosuppressive therapy at 24 months after HSCT. Immunization against rubella is especially important for female patients of reproductive age. Further studies will be necessary to evaluate the effect of vaccination on the antibody response in adult allogeneic HSCT recipients.

  13. [Fusarium solani infection in a patient after allogeneic hematopoietic stem cell transplantation: case report and literature review].

    Science.gov (United States)

    Hu, Jiang-Wei; Shu, Xiang-Rong; Ren, Jing; Yin, Xiu-Yun; Jiang, Min; Hu, Liang-Ding; Zhang, Bo; Chen, Hu

    2010-10-01

    To study Fusarium solani infection as a complication in patients after allogeneic hematopoietic stem cell transplantation and to discuss the diagnosis and appropriate therapy. Symptoms, physical examination, laboratory tests, computed tomographic (CT) scans, treatments and outcomes of Fusarium solani infection in a patient with acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation were retrospectively analyzed, and related literatures reviewed. The patient developed pulmonary infiltration and systemic multiple subcutaneous masses after allogeneic hematopoietic stem cell transplantation. Tissue biopsy smear showed a large number of hyphae and spores, and fungal culture grew Fusarium solani. The subcutaneous masses were incised and drained, while amphotericin B and voriconazole were administered, with granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) for hematopoietic recovery. The patient was discharge after full recovery. Fusarium solani infection is a rare but fatal complication after allogeneic hematopoietic stem cell transplantation. Once the skin lesions or subcutaneous masses developed, tissue smear and culture should be done as soon as possible. Early diagnosis and effective treatment to recovery of the patient after allogeneic hematopoietic stem cell transplant. Moreover, the recovery of adequate neutrophil levels is the most important factor in the resolution of fusarial infection.

  14. Allogeneic amniotic membrane-derived mesenchymal stromal cell transplantation in a porcine model of chronic myocardial ischemia

    Science.gov (United States)

    Kimura, M; Toyoda, M; Gojo, S; Itakura, Y; Kami, D; Miyoshi, S; Kyo, S; Ono, M; Umezawa, A

    2012-01-01

    Introduction. Amniotic membrane contains a multipotential stem cell population and is expected to possess the machinery to regulate immunological reactions. We investigated the safety and efficacy of allogeneic amniotic membrane-derived mesenchymal stromal cell (AMSC) transplantation in a porcine model of chronic myocardial ischemia as a preclinical trial. Methods. Porcine AMSCs were isolated from amniotic membranes obtained by cesarean section just before delivery and were cultured to increase their numbers before transplantation. Chronic myocardial ischemia was induced by implantation of an ameroid constrictor around the left circumflex coronary artery. Four weeks after ischemia induction, nine swine were assigned to undergo either allogeneic AMSC transplantation or normal saline injection. Functional analysis was performed by echocardiography, and histological examinations were carried out by immunohistochemistry 4 weeks after AMSC transplantation. Results. Echocardiography demonstrated that left ventricular ejection fraction was significantly improved and left ventricular dilatation was well attenuated 4 weeks after AMSC transplantation. Histological assessment showed a significant reduction in percentage of fibrosis in the AMSC transplantation group. Injected allogeneic green fluorescent protein (GFP)-expressing AMSCs were identified in the immunocompetent host heart without the use of any immunosuppressants 4 weeks after transplantation. Immunohistochemistry revealed that GFP colocalized with cardiac troponin T and cardiac troponin I. Conclusions. We have demonstrated that allogeneic AMSC transplantation produced histological and functional improvement in the impaired myocardium in a porcine model of chronic myocardial ischemia. The transplanted allogeneic AMSCs survived without the use of any immunosuppressants and gained cardiac phenotype through either their transdifferentiation or cell fusion. PMID:24693195

  15. Heterosexual and homosexual partners practising unprotected sex may develop allogeneic immunity and to a lesser extent tolerance.

    Science.gov (United States)

    Kingsley, Cherry; Peters, Barry; Babaahmady, Kaboutar; Pomeroy, Laura; Rahman, Durdana; Vaughan, Robert; Lehner, Thomas

    2009-11-23

    Epidemiological studies suggest that allogeneic immunity may inhibit HIV-1 transmission from mother to baby and is less frequent in multiparous than uniparous women. Alloimmune responses may also be elicited during unprotected heterosexual intercourse, which is associated ex vivo with resistance to HIV infection. The investigation was carried out in well-defined heterosexual and homosexual monogamous partners, practising unprotected sex and a heterosexual cohort practising protected sex. Allogeneic CD4(+) and CD8(+) T cell proliferative responses were elicited by stimulating PBMC with the partners' irradiated monocytes and compared with 3(rd) party unrelated monocytes, using the CFSE method. Significant increase in allogeneic proliferative responses was found in the CD4(+) and CD8(+) T cells to the partners' irradiated monocytes, as compared with 3(rd) party unrelated monocytes (pparty monocytes was consistent with tolerization, in both the heterosexual and homosexual partners (psex (psex (p = 0.02). Both heterosexual and homosexual monogamous partners practising unprotected sex develop allogeneic CD4(+) and CD8(+) T cell proliferative responses to the partners' unmatched cells and a minority may be tolerized. However, a greater proportion of homosexual rather than heterosexual partners developed CD4(+)CD25FoxP3(+) regulatory T cells. These results, in addition to finding greater inhibition of HIV-1 infectivity in PBMC ex vivo in heterosexual partners practising unprotected, compared with those practising protected sex, suggest that allogeneic immunity may play a significant role in the immuno-pathogenesis of HIV-1 infection.

  16. Allogeneic amniotic membrane-derived mesenchymal stromal cell transplantation in a porcine model of chronic myocardial ischemia

    Directory of Open Access Journals (Sweden)

    Kimura M

    2012-01-01

    Full Text Available Introduction. Amniotic membrane contains a multipotential stem cell population and is expected to possess the machinery to regulate immunological reactions. We investigated the safety and efficacy of allogeneic amniotic membrane-derived mesenchymal stromal cell (AMSC transplantation in a porcine model of chronic myocardial ischemia as a preclinical trial. Methods. Porcine AMSCs were isolated from amniotic membranes obtained by cesarean section just before delivery and were cultured to increase their numbers before transplantation. Chronic myocardial ischemia was induced by implantation of an ameroid constrictor around the left circumflex coronary artery. Four weeks after ischemia induction, nine swine were assigned to undergo either allogeneic AMSC transplantation or normal saline injection. Functional analysis was performed by echocardiography, and histological examinations were carried out by immunohistochemistry 4 weeks after AMSC transplantation. Results. Echocardiography demonstrated that left ventricular ejection fraction was significantly improved and left ventricular dilatation was well attenuated 4 weeks after AMSC transplantation. Histological assessment showed a significant reduction in percentage of fibrosis in the AMSC transplantation group. Injected allogeneic green fluorescent protein (GFP-expressing AMSCs were identified in the immunocompetent host heart without the use of any immunosuppressants 4 weeks after transplantation. Immunohistochemistry revealed that GFP colocalized with cardiac troponin T and cardiac troponin I. Conclusions. We have demonstrated that allogeneic AMSC transplantation produced histological and functional improvement in the impaired myocardium in a porcine model of chronic myocardial ischemia. The transplanted allogeneic AMSCs survived without the use of any immunosuppressants and gained cardiac phenotype through either their transdifferentiation or cell fusion.

  17. Cellular bone matrices: viable stem cell-containing bone graft substitutes.

    Science.gov (United States)

    Skovrlj, Branko; Guzman, Javier Z; Al Maaieh, Motasem; Cho, Samuel K; Iatridis, James C; Qureshi, Sheeraz A

    2014-11-01

    Advances in the field of stem cell technology have stimulated the development and increased use of allogenic bone grafts containing live mesenchymal stem cells (MSCs), also known as cellular bone matrices (CBMs). It is estimated that CBMs comprise greater than 17% of all bone grafts and bone graft substitutes used. To critically evaluate CBMs, specifically their technical specifications, existing published data supporting their use, US Food and Drug Administration (FDA) regulation, cost, potential pitfalls, and other aspects pertaining to their use. Areview of literature. A series of Ovid, Medline, and Pubmed-National Library of Medicine/National Institutes of Health (www.ncbi.nlm.nih.gov) searches were performed. Only articles in English journals or published with English language translations were included. Level of evidence of the selected articles was assessed. Specific technical information on each CBM was obtained by direct communication from the companies marketing the individual products. Five different CBMs are currently available for use in spinal fusion surgery. There is a wide variation between the products with regard to the average donor age at harvest, total cellular concentration, percentage of MSCs, shelf life, and cell viability after defrosting. Three retrospective studies evaluating CBMs and fusion have shown fusion rates ranging from 90.2% to 92.3%, and multiple industry-sponsored trials are underway. No independent studies evaluating spinal fusion rates with the use of CBMs exist. All the commercially available CBMs claim to meet the FDA criteria under Section 361, 21 CFR Part 1271, and are not undergoing FDA premarket review. The CBMs claim to provide viable MSCs and are offered at a premium cost. Numerous challenges exist in regard to MSCs' survival, function, osteoblastic potential, and cytokine production once implanted into the intended host. Cellular bone matrices may be a promising bone augmentation technology in spinal fusion surgery

  18. Bone lesion biopsy

    Science.gov (United States)

    Bone biopsy; Biopsy - bone ... used to guide the exact placement of the biopsy instrument. The health care provider applies a numbing ... is sent to a lab for examination. Bone biopsy may also be done under general anesthesia to ...

  19. Anorexia nervosa and bone

    National Research Council Canada - National Science Library

    Misra, Madhusmita; Klibanski, Anne

    2014-01-01

    Anorexia nervosa (AN) is a condition of severe low weight that is associated with low bone mass, impaired bone structure, and reduced bone strength, all of which contribute to increased fracture risk...

  20. Papineau debridement, Ilizarov bone transport, and negative-pressure wound closure for septic bone defects of the tibia.

    Science.gov (United States)

    Karargyris, Orestis; Polyzois, Vasilios D; Karabinas, Panayiotis; Mavrogenis, Andreas F; Pneumaticos, Spyros G

    2014-08-01

    Ilizarov pioneered bone transport using a circular external fixator. Papineau described a staged technique for the treatment for infected pseudarthrosis of the long bones. This article presents a single-stage Papineau technique and Ilizarov bone transport, and postoperative negative-pressure wound dressing changes for septic bone defects of the tibia. We studied the files of seven patients (mean age, 32 years) with septic bone defects of the tibia treated with a Papineau technique and Ilizarov bone transport in a single stage, followed by postoperative negative-pressure wound dressing changes. All patients had septic pseudarthrosis and skin necrosis of the tibia. The technique included a single-stage extensive surgical debridement of necrotic bone, open bone grafting with cancellous bone autograft and bone transport, and postoperative negative-pressure wound dressing changes for wound closure. The mean time from the initial injury was 6 months (range, 4-8 months). The mean follow-up was 14 months (range, 10-17 months). All patients experienced successful wound healing at a mean of 29 days. Six patients experienced successful bone regeneration and union at the docking side at a mean of 6 months. One patient experienced delayed union at the docking site, which was treated with autologous cancellous bone grafting. Two patients experienced pin track infection, which was successfully treated with antibiotics and pin site dressing changes. All patients were able to return to their work and previous levels of activity, except one patient who had a stiff ankle joint and had to change his job. No patient experienced recurrence of infection, or fracture of the regenerated or transported bone segment until the period of this study. The combined Papineau and Ilizarov bone transport technique with negative-pressure wound closure provides for successful eradication of the infection, reconstruction of the bone defect, and soft-tissue closure. A single-stage surgical treatment is

  1. Achievement of disease control with donor-derived EB virus-specific cytotoxic T cells after allogeneic peripheral blood stem cell transplantation for aggressive NK-cell leukemia.

    Science.gov (United States)

    Haji, Shojiro; Shiratsuchi, Motoaki; Matsushima, Takamitsu; Takamatsu, Akiko; Tsuda, Mariko; Tsukamoto, Yasuhiro; Tanaka, Emi; Ohno, Hirofumi; Fujioka, Eriko; Ishikawa, Yuriko; Imadome, Ken-Ichi; Ogawa, Yoshihiro

    2017-04-01

    Aggressive NK-cell leukemia (ANKL) is characterized by systemic infiltration of Epstein-Barr virus (EBV)-associated natural killer cells and poor prognosis. We report a case of ANKL in which EBV-specific cytotoxic T lymphocytes (CTLs) were induced. A 41-year-old male suffered from fever, pancytopenia, and hepatosplenomegaly. The number of abnormal large granular lymphocytes in the bone marrow was increased and the cells were positive for CD56 and EBV-encoded small nuclear RNAs. The patient was diagnosed with ANKL and achieved a complete response following intensive chemotherapy. He then underwent allogeneic peripheral blood stem cell transplantation from his sister. Conditioning therapy consisted of total body irradiation and cyclophosphamide. Graft-versus-host disease prophylaxis consisted of cyclosporine and methotrexate. On day 31, complete donor chimerism was achieved and no acute graft-versus-host disease developed. The ANKL relapsed on day 80, and cyclosporine was rapidly tapered and chemotherapy was started. During hematopoietic recovery, the number of atypical lymphocytes increased, but they were donor-derived EBV-specific CTLs. The patient achieved a partial response and EBV viral load decreased to normal range. Unfortunately, ANKL worsen again when the CTLs disappeared from his blood. This is the first case report of ANKL in which induced EBV-specific CTLs may have contributed to disease control.

  2. Factors predicting outcome after allogeneic transplant in refractory acute myeloid leukemia: a retrospective analysis of Gruppo Italiano Trapianto di Midollo Osseo (GITMO).

    Science.gov (United States)

    Todisco, E; Ciceri, F; Boschini, C; Giglio, F; Bacigalupo, A; Patriarca, F; Donnini, I; Alessandrino, E P; Arcese, W; Iori, A P; Marenco, P; Cavattoni, I; Chiusolo, P; Terruzzi, E; Castagna, L; Santoro, A; Bosi, A; Oldani, E; Bruno, B; Bonifazi, F; Rambaldi, A

    2017-07-01

    The clinical outcome of primary refractory (PRF) AML patients is poor and only a minor proportion of patients is rescued by allogenic hematopoietic stem cell transplantation (HSCT). The identification of pre-HSCT variables may help to determine PRF AML patients who can most likely benefit from HSCT. We analyzed PRF AML patients transplanted between 1999 and 2012 from a sibling, unrelated donor or a cord blood unit. Overall, 227 patients from 26 Gruppo Italiano Trapianto di Midollo Osseo e Terapia cellulare centers were included in the analysis. At 3 years, the overall survival was 14%. By multivariate analysis, the number of chemotherapy cycles, (hazard ratio (HR): 1.87; 95% confidence interval (CI): 1.24-2.85; P=0.0028), the percentage of bone marrow or peripheral blood blasts (HR: 1.75; 95% CI: 1.16-2.64; P=0.0078), the adverse cytogenetic (HR: 1.44; 95% CI: 1.00-2.07; P=0.0508) and the age of patients (HR: 1.77; 95% CI: 1.08-2.88; P=0.0223) remained significantly associated with survival. Thus, we set up a new score predicting at 3 years after transplantation, an overall survival probability of 32% for patients with score 0 (no or 1 prognostic factor), 10% for patients with score 1 (2 prognostic factors) and 3% for patients with score 2 (3 or 4 prognostic factors).

  3. HHV-6 infection after allogeneic hematopoietic stem cell transplantation: From chromosomal integration to viral co-infections and T-cell reconstitution patterns.

    Science.gov (United States)

    Quintela, Adrien; Escuret, Vanessa; Roux, Sandrine; Bonnafous, Pascale; Gilis, Lila; Barraco, Fiorenza; Labussière-Wallet, Hélène; Duscastelle-Leprêtre, Sophie; Nicolini, Franck-Emmanuel; Thomas, Xavier; Chidiac, Christian; Ferry, Tristan; Frobert, Emilie; Morisset, Stéphane; Poitevin-Later, Françoise; Monneret, Guillaume; Michallet, Mauricette; Ader, Florence

    2016-02-01

    Human herpes virus 6 (HHV-6) can reactivate after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and may be associated with significant clinical manifestations. Case control study of HHV-6 infections after allo-HSCT. Chromosomal integration (ciHHV-6) for viral loads ≥ 5.5-log10 copies/mL was investigated. Viral co-infections, T-cell recovery, risk factors and outcome were compared in HHV-6- and non-HHV-6-infected patients. Antiviral treatment strategies were reviewed. Among 366 adult allo-HSCT recipients, 75 HHV-6 infections occurred. Three (4%) recipients were ciHHV-6. HHV-6 infections were associated with CMV (p = 0.05; sdHR 1.73, CI 0.99-3.02) and/or BKV infections (p cells recovery was observed until 6 months after allo-HSCT in the HHV-6-infected group (p bone marrow recipients (p = 0.0007; sdHR 3.82, CI 1.76-8.27). Anti-HHV-6 treatment achieved complete response in only 2/3 of the cases. In this series of allo-HSCT recipients, 4% were ciHHV-6, active HHV-6 infection was likely associated with CMV and BKV co-reactivations, delayed CD8+ T-cell recovery and poorer outcome. Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  4. Inhibition of IL-32 activation by alpha-1 antitrypsin suppresses alloreactivity and increases survival in an allogeneic murine marrow transplantation model.

    NARCIS (Netherlands)

    Marcondes, A.M.; Li, X.; Tabellini, L.; Bartenstein, M.; Kabacka, J.; Sale, G.E.; Hansen, J.A.; Dinarello, C.A.; Deeg, H.J.

    2011-01-01

    Interleukin (IL)-32 was originally identified in natural killer cells and IL-2-activated human T lymphocytes. As T cells are activated in allogeneic transplantation, we determined the role of IL-32 in human mixed lymphocyte cultures (MLCs) and GVHD. In allogeneic MLCs, IL-32 increased two-fold in

  5. Immune reconstitution after allogeneic hematopoietic stem cell transplantation in children: a single institution study of 59 patients

    Directory of Open Access Journals (Sweden)

    Hyun O Kim

    2013-01-01

    Full Text Available &lt;b&gt;Purpose:&lt;/b&gt; Lymphocyte subset recovery is an important factor that determines the success of hematopoietic stem cell transplantation (HSCT. Temporal differences in the recovery of lymphocyte subsets and the factors influencing this recovery are important variables that affect a patient's posttransplant immune reconstitution, and therefore require investigation. &lt;b&gt;Methods:&lt;/b&gt; The time taken to achieve lymphocyte subset recovery and the factors influencing this recovery were investigated in 59 children who had undergone HSCT at the Department of Pediatrics, The Catholic University of Korea Seoul St. Mary's Hospital, and who had an uneventful follow-up period of at least 1 year. Analyses were carried out at 3 and 12 months post-transplant. An additional study was performed 1 month post-transplant to evaluate natural killer (NK cell recovery. The impact of preand post-transplant variables, including diagnosis of Epstein-Barr virus (EBV DNAemia posttransplant,on lymphocyte recovery was evaluated. &lt;b&gt;Results:&lt;/b&gt; The lymphocyte subsets recovered in the following order: NK cells, cytotoxic T cells, B cells,and helper T cells. At 1 month post-transplant, acute graft-versus-host disease was found to contribute significantly to the delay of CD16+/56+ cell recovery. Younger patients showed delayed recovery of both CD3+/CD8+ and CD19+ cells. EBV DNAemia had a deleterious impact on the recovery of both CD3+ and CD3+/CD4+ lymphocytes at 1 year post-transplant. &lt;b&gt;Conclusion:&lt;/b&gt; In our pediatric allogeneic HSCT cohort, helper T cells were the last subset to recover. Younger age and EBV DNAemia had a negative impact on the post-transplant recovery of T cells and B cells.

  6. [Indications, technique and risks in bone marrow transplantation in adulthood].

    Science.gov (United States)

    Heyll, A; Söhngen, D; Minning, H; Meckenstock, G; Aul, C; Schneider, W

    1996-03-19

    The option of bone marrow transplantation (BMT) significantly improved prognosis of adult patients with hematologic malignancies aged less than 50 years. Allogeneic BMT using the marrow of an HLA-identical family member still provides the most effective method of BMT. Conventional indications for this form of BMT are chronic myeloid leukemia (CML), acute leukemias presenting with adverse risk factors, myelodysplastic syndromes and severe aplastic anemia. If performed early in the disease course (e.g. during the chronic phase of CML or first remission of acute leukemia and MDS) allogeneic BMT cures 50 to 60% of patients. About 20% die of therapy related complications, e.g. graft versus host disease (GvHD), fatal infections or venoocclusive disease of the liver (VOD) and about 20% of patients succumb to relapse of their hematologic disorder. 80% presenting with severe aplastic anemia can be cured, if allogeneic BMT is performed soon after diagnosis without previous immunosuppressive therapy and blood transfusions. BMT with the marrow of a matched unrelated donor or autologous BMT are increasingly used as alternative procedures. A rate of lethal complications as high as 50% hinders rapid extension of BMT with unrelated donors. Therefore, this form of BMT should be restricted to young patients with leukemias, who cannot achieve long-term remission with conventional chemotherapy (in case of acute leukemias) or alpha-interferon (in case of CML). Reconstitution of hematopoiesis is more rapid after peripheral blood stem cell transplantation (PBSCT) compared with autologous BMT. Therefore, PBSCT will replace autologous BMT in most cases. Most favourable results of PBSCT have been reported in patients with malignant lymphomas after relapse or inferior response to primary induction therapy. Due to the higher relapse rate autologous BMT is inferior to allogeneic BMT in leukemia patients. Trials are required to clarify the potential role of myeloablative therapy with stem cell

  7. Increasing the efficacy of antitumor glioma vaccines by photodynamic therapy and local injection of allogeneic glioma cells

    Science.gov (United States)

    Christie, Catherine E.; Peng, Qian; Madsen, Steen J.; Uzal, Francisco A.; Hirschberg, Henry

    2016-03-01

    Immunotherapy of brain tumors involves the stimulation of an antitumor immune response. This type of therapy can be targeted specifically to tumor cells thus sparing surrounding normal brain. Due to the presence of the blood-brain barrier, the brain is relatively isolated from the systemic circulation and, as such, the initiation of significant immune responses is more limited than other types of cancers. The purpose of this study was to show that the efficacy of tumor primed antigen presenting macrophage vaccines could be increased by: (1) PDT of the priming tumor cells, and (2) injection of allogeneic glioma cells directly into brain tumors. Experiments were conducted in an in vivo brain tumor model using Fisher rats and BT4C (allogeneic) and F98 (syngeneic) glioma cells. Preliminary results showed that vaccination alone had significantly less inhibitory effect on F98 tumor growth compared to the combination of vaccination and allogeneic cell (BT4C) injection.

  8. Sequential Onset of Varicella-Zoster Virus Encephalomeningitis and Progressive Multifocal Leukoencephalopathy in an Allogeneic Hematopoietic Stem Cell Transplant Recipient.

    Science.gov (United States)

    Yamashita, Yukiko; Kusakabe, Shinsuke; Toda, Jun; Ohshima, Kenji; Masaie, Hiroaki; Yagi, Toshinari; Yoshida, Hitoshi; Ishikawa, Jun

    2016-12-12

    Here, we describe a case of sequential varicella-zoster virus encephalomeningitis and progressive multifocal leukoencephalopathy following an allogeneic hematopoietic stem cell transplant procedure. A 37-year-old male patient presented with fever, incomplete paralysis of bilateral legs, and bullous eruptions 8 months after allogeneic transplant. Polymerase chain reaction assays of cerebrospinal fluid samples for varicella-zoster virus were positive. Bullous eruptions and incomplete paralysis of bilateral legs improved after administration of acyclovir. However, higher brain dysfunction was present and getting worse. We detected no herpes simplex virus, varicella-zoster virus, Cytomegalovirus, human herpes virus 6, Epstein-Barr virus, or JC virus in cerebrospinal fluid samples with polymerase chain reaction assays. Pathologic findings and polymerase chain reaction assays with brain biopsy samples revealed that the patient had progressive multifocal leukoencephalopathy. This is the first report of a case showing dual central nervous system infections due to varicella-zoster virus and JC virus after allogeneic stem cell transplant.

  9. Allogenic human serum, a clinical grade serum supplement for promoting human periodontal ligament stem cell expansion.

    Science.gov (United States)

    Arpornmaeklong, Premjit; Sutthitrairong, Chotika; Jantaramanant, Piyathida; Pripatnanont, Prisana

    2016-12-13

    Exposing human periodontal ligament stem cells (hPDLSCs) to animal proteins during cell expansion would compromise quality and safety of the hPDLSCs for clinical applications. The current study aimed to evaluate the replacement of animal-based serum by human serum for the expansion of hPDLSCs. hPDLSCs were cultured in culture media supplemented with four types of serums: Group A: fetal bovine serum (FBS); Group B: allogeneic human male AB serum (HS); Group C: in-house autologous (Auto-HS); and Group D: in-house allogeneic human serums (Allo-HS). Exhibitions of mesenchymal stem cell characteristics of hPDLSCs were examined. Then, growth and osteogenic (OS) differentiation potential of hPDLSCs in FBS and HS at passages 5 and 15 were compared to investigate the effects of serum supplements on growth and expansion stability of the expanded hPDLSCs. After that, growth and OS differentiation of hPDLSCs in Auto- and Allo-HS were investigated. Flow cytometrical analyses, functional differentiations, cell growth kinetic, cytogenetic analysis, alkaline phosphatase and calcium content assays, and oil red O and von Kossa staining were performed. Results showed that at passage 5, HS promoted growth and OS differentiation of hPDLSCs and extensive cell expansion, decreased growth and differentiation potential of the expanded hPDLSCs, particularly in HS. Growth and OS differentiation of hPDLSCs in Auto-HS and Allo-HS were not different. In summary, allogeneic human serum could be a replacement to FBS for hPDLSC expansion. In vitro cell expansion of hPDLSCs should be minimal to ensure optimal cell quality. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  10. Distress screening in allogeneic hematopoietic stem cell (HSCT) caregivers and patients.

    Science.gov (United States)

    Bevans, Margaret; Wehrlen, Leslie; Prachenko, Olena; Soeken, Karen; Zabora, James; Wallen, Gwenyth R

    2011-06-01

    Family caregivers of allogeneic hematopoietic stem cell transplant (HSCT) patients are at risk for experiencing significant psychological distress yet screening caregivers has not been well studied. This analysis explored the psychometric characteristics of the Distress Thermometer (DT) by examining its relationship, sensitivity, and specificity relative to the Brief Symptom Inventory 18 (BSI-18) and the Multidimensional Fatigue Symptom Inventory (MFSI) in a sample of allogeneic HSCT caregivers and patients. Longitudinal data were drawn from an ongoing intervention study for HSCT caregivers and patients. Data from one hundred and fifty-six English-speaking adults where patients (n = 65) were receiving their first allogeneic HSCT with at least one adult caregiver (n = 91) were eligible for this analysis. Study questionnaires were administered at baseline, initial discharge, and 6 weeks following discharge. Construct validity was supported by significant relationships (pcaregivers and patients. The diagnostic utility of the DT for patients was good (AUC = 0.85±0.05, p = 0.001), while for caregivers it was poor (AUC = 0.61±0.08, p = 0.28). A DT cut point of 5 was supported for patients (sensitivity = 1.0, specificity = 0.68), while for caregivers there was less confidence (sensitivity = 0.70, specificity = 0.52). Caregivers and patients reporting a higher number of problems had a greater level of distress (pcaregivers and patients. Although the diagnostic utility of the DT for HSCT caregivers may be limited, understanding factors associated with distress can guide practice for this understudied population. Copyright © 2011 John Wiley & Sons, Ltd.

  11. Mechanisms of Tolerance to Parental Parathyroid Tissue when Combined with Human Allogeneic Thymus Transplantation

    Science.gov (United States)

    Chinn, Ivan K.; Olson, John A.; Skinner, Michael A.; McCarthy, Elizabeth A.; Gupton, Stephanie E.; Chen, Dong-Feng; Bonilla, Francisco A.; Roberts, Robert L.; Kanariou, Maria G.; Devlin, Blythe H.; Markert, M. Louise

    2010-01-01

    Background The induction of tolerance toward third-party solid organ grafts with allogeneic thymus tissue transplantation has not been previously demonstrated in human subjects. Objective Infants with complete DiGeorge anomaly (having neither thymus nor parathyroid function) were studied for conditions and mechanisms required for the development of tolerance to third-party solid organ tissues. Methods Four infants who met criteria received parental parathyroid with allogeneic thymus transplantation and were studied. Results Two of three survivors showed function of both grafts but subsequently lost parathyroid function. They demonstrated alloreactivity against the parathyroid donor in mixed lymphocyte cultures. For these 2 recipients, parathyroid donor HLA class II alleles were mismatched with the recipient and thymus. MHC class II tetramers confirmed the presence of recipient CD4+ T cells with specificity towards a mismatched parathyroid donor class II allele. The third survivor has persistent graft function and lacks alloreactivity towards the parathyroid donor. All parathyroid donor class II alleles were shared with either the recipient or the thymus graft, with minor differences between the parathyroid (HLA-DRB1*1104) and thymus (HLA-DRB1*1101). Tetramer analyses detected recipient T cells specific for the parathyroid HLA-DRB1*1104 allele. Alloreactivity towards the parathyroid donor was restored with low-doses of IL-2. Conclusion Tolerance toward parathyroid grafts in combined parental parathyroid and allogeneic thymus transplantation requires matching of thymus tissue to parathyroid HLA class II alleles to promote negative selection and suppression of recipient T cells that have alloreactivity toward the parathyroid grafts. This matching strategy may be applied toward tolerance induction in future combined thymus and solid organ transplantation efforts. PMID:20832849

  12. A Characterization of the Oral Microbiome in Allogeneic Stem Cell Transplant Patients

    Science.gov (United States)

    Ames, Nancy J.; Sulima, Pawel; Ngo, Thoi; Barb, Jennifer; Munson, Peter J.; Paster, Bruce J.; Hart, Thomas C.

    2012-01-01

    Background The mouth is a complex biological structure inhabited by diverse bacterial communities. The purpose of this study is to describe the effects of allogeneic stem cell transplantation on the oral microbiota and to examine differences among those patients who acquired respiratory complications after transplantation. Methodology/Principal Findings All patients were consented at the National Institutes of Health, Clinical Center. Bacterial DNA was analyzed from patients' oral specimens using the Human Oral Microbe Identification Microarray. The specimens were collected from four oral sites in 45 allogeneic transplantation patients. Specimens were collected at baseline prior to transplantation, after transplantation at the nadir of the neutrophil count and after myeloid engraftment. If respiratory signs and symptoms developed, additional specimens were obtained. Patients were followed for 100 days post transplantation. Eleven patients' specimens were subjected to further statistical analysis. Many common bacterial genera, such as Streptococcus, Veillonella, Gemella, Granulicatella and Camplyobacter were identified as being present before and after transplantation. Five of 11 patients developed respiratory complications following transplantation and there was preliminary evidence that the oral microbiome changed in their oral specimens. Cluster analysis and principal component analysis revealed this change in the oral microbiota. Conclusions/Significance After allogeneic transplantation, the oral bacterial community's response to a new immune system was not apparent and many of the most common core oral taxa remained unaffected. However, the oral microbiome was affected in patients who developed respiratory signs and symptoms after transplantation. The association related to the change in the oral microbiota and respiratory complications after transplantation will be validated by future studies using high throughput molecular methods. PMID:23144704

  13. Equine allogeneic chondrogenic induced mesenchymal stem cells: A GCP target animal safety and biodistribution study.

    Science.gov (United States)

    Broeckx, S Y; Spaas, J H; Chiers, K; Duchateau, L; Van Hecke, L; Van Brantegem, L; Dumoulin, M; Martens, A M; Pille, F

    2017-12-27

    The safety of the intra-articular use of mesenchymal stem cells (MSCs) is scarcely reported. Therefore, the goal of this study was to investigate the safety of a single intra-articular injection with allogeneic chondrogenic induced MSCs combined with equine plasma (=the investigational product: IVP) compared to a saline (0.9% NaCl) placebo control (=control product: CP). Sixteen healthy experimental horses were randomly assigned to receive a single intra-articular injection with either the IVP (n=8) or the CP (n=8) in the left metacarpophalangeal joint. All horses underwent a daily clinical assessment throughout the entire study period of 42days to assess adverse events. Additionally, a local joint