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  1. Stem Cell Transplant

    Science.gov (United States)

    ... transplant is a procedure that infuses healthy blood stem cells into your body to replace your damaged or ... A bone marrow transplant is also called a stem cell transplant. A bone marrow transplant may be necessary ...

  2. Stem Cell Transplants (For Teens)

    Science.gov (United States)

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Stem Cell Transplants KidsHealth > For Teens > Stem Cell Transplants Print ... Does it Take to Recover? Coping What Are Stem Cells? As you probably remember from biology class, every ...

  3. Stem cells in cell transplantation.

    Science.gov (United States)

    Sanmartin, Agneta; English, Denis; Sanberg, Paul R

    2006-12-01

    This commentary documents the increased number of stem cell-related research reports recently published in the cell transplantation field in the journal Cell Transplantation. The journal covers a wide range of issues in cell-based therapy and regenerative medicine and is attracting clinical and preclinical articles from around the world. It thereby complements and extends the basic coverage of stem cell physiology reported in Stem Cells and Development. Sections in Cell Transplantation cover neuroscience, diabetes, hepatocytes, bone, muscle, cartilage, skin, vessels, and other tissues, as well as tissue engineering that employs novel methods with stem cells. Clearly, the continued use of biomedical engineering will depend heavily on stem cells, and these two journals are well positioned to provide comprehensive coverage of these developments.

  4. Stem Cell Transplants (For Parents)

    Science.gov (United States)

    ... Old Feeding Your 1- to 2-Year-Old Stem Cell Transplants KidsHealth > For Parents > Stem Cell Transplants Print A A A What's in this ... Recovery Coping en español Trasplantes de células madre Stem cells are cells in the body that have the ...

  5. Cell transplantation for Parkinson's disease

    Institute of Scientific and Technical Information of China (English)

    Jia Liu; Hongyun Huang

    2006-01-01

    OBJECTIVE: The motor symptoms of Parkinson's disease (PD) can be improved by cell transplantation,which has caught general attention from the field of the therapy for PD recently. In this paper, we summarize the cell-based therapy for PD.DATA SOURCES: A search for English literature related to the cellular transplantation of PD from January 1979to July 2006 was conducted in Medline with the key words of "Parkinson's disease, cell transplantation,embryonic stem cells, neural stem cells".STUDY SELECTTON: Data were checked in the first trial, and literatures about PD and cell transplantation were selected. Inclusive criteria: ① PD; ② Cell transplantation. Exclusive criteria: repetitive researches.DATA EXTRACTTON: A total of 100 papers related to cellular transplant and PD were collected and 41literatures were in accordance with the inclusive criteria.DATA SYNTHESIS: PD is a neural degeneration disease that threatens the health of the aged people, and most traditional therapeusis cannot delay its pathological proceeding. Cell transplantation is becoming popular as a new therapeutic tool, and the cells used to transplant mainly included dopamine-secreting cells, fetal ventral mesencephalic cells, embryonic stem cells and neural stem cells up to now. Animal experiment and clinical test demonstrate that cell transplantation can relieve the motor symptoms of Parkinson's disease obviously, but there are some problems need to be solved.CONCLUSTON: Cell transplantation has visible therapeutic efficacy on PD. Following the improvement of technique, and we have enough cause to credit that cell therapy may cure PD in the future.

  6. Stem cells and transplant arteriosclerosis.

    Science.gov (United States)

    Xu, Qingbo

    2008-05-09

    Stem cells can differentiate into a variety of cells to replace dead cells or to repair damaged tissues. Recent evidence indicates that stem cells are involved in the pathogenesis of transplant arteriosclerosis, an alloimmune initiated vascular stenosis that often results in transplant organ failure. Although the pathogenesis of transplant arteriosclerosis is not yet fully understood, recent developments in stem cell research have suggested novel mechanisms of vascular remodeling in allografts. For example, stem cells derived from the recipient may repair damaged endothelial cells of arteries in transplant organs. Further evidence suggests that stem cells or endothelial progenitor cells may be released from both bone marrow and non-bone marrow tissues. Vascular stem cells appear to replenish cells that died in donor vessels. Concomitantly, stem/progenitor cells may also accumulate in the intima, where they differentiate into smooth muscle cells. However, several issues concerning the contribution of stem cells to the pathogenesis of transplant arteriosclerosis are controversial, eg, whether bone marrow-derived stem cells can differentiate into smooth muscle cells that form neointimal lesions of the vessel wall. This review summarizes recent research on the role of stem cells in transplant arteriosclerosis, discusses the mechanisms of stem cell homing and differentiation into mature endothelial and smooth muscle cells, and highlights the controversial issues in the field.

  7. Stem Cell Transplant Patients and Fungal Infections

    Science.gov (United States)

    ... Foodborne, Waterborne, and Environmental Diseases Mycotic Diseases Branch Stem Cell Transplant Patients and Fungal Infections Recommend on Facebook ... Mold . Top of Page Preventing fungal infections in stem cell transplant patients Fungi are difficult to avoid because ...

  8. Organ or Stem Cell Transplant and Your Mouth

    Science.gov (United States)

    ... Stem Cell Transplant and Your Mouth Organ or Stem Cell Transplant and Your Mouth Main Content Key Points​ ... Your Dentist Before Transplant Before an organ or stem cell transplant, have a dental checkup. Your mouth should ...

  9. T cell depleted haploidentical transplantation: positive selection

    Directory of Open Access Journals (Sweden)

    Franco Aversa

    2011-06-01

    Full Text Available Interest in mismatched transplantation arises from the fact that a suitable one-haplotype mismatched donor is immediately available for virtually all patients, particularly for those who urgently need an allogenic transplant. Work on one haplotype-mismatched transplants has been proceeding for over 20 years all over the world and novel transplant techniques have been developed. Some centres have focused on the conditioning regimens and post transplant immune suppression; others have concentrated on manipulating the graft which may be a megadose of extensively T celldepleted or unmanipulated progenitor cells. Excellent engraftment rates are associated with a very low incidence of acute and chronic GVHD and regimen-related mortality even in patients who are over 50 years old. Overall, event-free survival and transplant-related mortality compare favourably with reports on transplants from sources of stem cells other than the matched sibling.

  10. Stem Cell Transplants in Cancer Treatment

    Science.gov (United States)

    Stem cell transplants are procedures that restore blood-forming stem cells in cancer patients who have had theirs destroyed by very high doses of chemotherapy or radiation therapy. Learn about the types of transplants and side effects that may occur.

  11. PARASITIC INFECTIONS IN HEMATOPOIETIC STEM CELL TRANSPLANTATION

    Directory of Open Access Journals (Sweden)

    Isidro Jarque

    2016-07-01

    Full Text Available Parasitic infections are rarely documented in hematopoietic stem cell transplant recipients. However, they may be responsible for fatal complications that are only diagnosed at autopsy. Increased awareness of the possibility of parasitic diseases both in autologous and allogeneic stem cell transplant patients is relevant not only for implementing preventive measures but also for performing an early diagnosis and starting appropriate therapy for these unrecognized but fatal infectious complications in hematopoietic transplant recipients. In this review, we will focus on parasitic diseases occurring in this population especially those with major clinical relevance including toxoplasmosis, American trypanosomiasis, leishmaniasis, malaria, and strongyloidiasis, among others, highlighting the diagnosis and management in hematopoietic transplant recipients.

  12. Blood-Forming Stem Cell Transplants

    Science.gov (United States)

    ... to Ask about Your Treatment Research Blood-Forming Stem Cell Transplants On This Page What are bone marrow ... Considering becoming a bone marrow or a blood stem cell donor? View this video on YouTube. Follow a ...

  13. Imaging in haematopoietic stem cell transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Evans, A.; Steward, C.G.; Lyburn, I.D.; Grier, D.J

    2003-03-01

    Haematopoietic stem cell transplantation (SCT) is used to treat a wide range of malignant and non-malignant haematological conditions, solid malignancies, and metabolic and autoimmune diseases. Although imaging has a limited role before SCT, it is important after transplantation when it may support the clinical diagnosis of a variety of complications. It may also be used to monitor the effect of therapy and to detect recurrence of the underlying disease if the transplant is unsuccessful. We present a pictorial review of the imaging of patients who have undergone SCT, based upon 15 years experience in a large unit performing both adult and paediatric transplants.

  14. Bone marrow transplant

    Science.gov (United States)

    Transplant - bone marrow; Stem cell transplant; Hematopoietic stem cell transplant; Reduced intensity nonmyeloablative transplant; Mini transplant; Allogenic bone marrow transplant; Autologous bone marrow transplant; Umbilical ...

  15. Related Hematopoietic Stem Cell Transplantation (HSCT) for Genetic Diseases of Blood Cells

    Science.gov (United States)

    2016-05-11

    Stem Cell Transplantation; Bone Marrow Transplantation; Peripheral Blood Stem Cell Transplantation; Allogeneic Transplantation,; Genetic Diseases; Thalassemia; Pediatrics; Diamond-Blackfan Anemia; Combined Immune Deficiency; Wiskott-Aldrich Syndrome; Chronic Granulomatous Disease; X-linked Lymphoproliferative Disease; Metabolic Diseases

  16. [Hepatic cell transplantation. Technical and methodological aspects].

    Science.gov (United States)

    Pareja, Eugenia; Martínez, Amparo; Cortés, Miriam; Bonora, Ana; Moya, Angel; Sanjuán, Fernando; Gómez-Lechón, M José; Mir, José

    2010-03-01

    Hepatic cell transplantation consists of grafting already differentiated cells such as hepatocytes. Human hepatocytes are viable and functionally active. Liver cell transplantation is carried out by means of a 3-step method: isolation of hepatocytes from donor liver rejected for orthotopic transplantation, preparing a cell suspension for infusion and, finally, hepatocytes are implanted into the recipient. There are established protocols for the isolation of human hepatocytes from unused segments of donor livers, based on collagenase digestion of cannulated liver tissue at 37 degrees C. The hepatocytes can be used fresh or cryopreserved. Cryopreservation of isolated human hepatocytes would then be available for planned use. In cell transplant, the important aspects are: infusion route, number of cells, number of infusions and viability of the cells. The cells are infused into the patient through a catheter inserted via portal vein or splenic artery. Liver cell transplantation allows liver tissue to be used that would, otherwise, be discarded, enabling multiple patients to be treated with hepatocytes from a single tissue donor.

  17. Germ cell transplantation in infertility mouse

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    This work investigated the spermatogenesis in an infertility BALB/c-nu mouse model by reinfusing germline stem cells into seminiferous tubules.Donor germ cells were isolated from male FVB/NJ-GFP transgenic mice.Seminiferous tubule microiniection was applied to achieve intratubular germ cell transfer.The germ cells were injected into exposed testes of the infertility mice.We used green fluorescence and DNA analysis of donor cells from GFP transgenic mice as genetic marker.The natural mating and Southern blot methods were applied to analyze the effect of sperm cell transplantation and the sperm function after seminiferous tubule microinjecUon.The spermatogenesis was morphologically observed from the seminiferous tubules in 41/60(68.33%)of the injected recipient mice using allogeneic donor cells.In the colonized testes,matured spermatozoa were seen in the lumen of the seminiferous tubules.In this research,BALB/c-nu infertility mouse model,the recipient animal,was used to avoid immunological rejection of donor cells,and germ cell transplantation was applied to overcome infertility caused by busulfan treatment.These results demonstrate that this technique of germ cell transplantation is of great use.Germ cell transplantation could be potentially valuable to oncological patients.

  18. Consideration of strategies for hematopoietic cell transplantation.

    Science.gov (United States)

    Yaniv, Isaac; Ash, Shifra; Farkas, Daniel L; Askenasy, Nadir; Stein, Jerry

    2009-01-01

    Bone marrow transplantation has been adoptively transferred from oncology to the treatment of autoimmune disorders. Along with extension of prevalent transplant-related concepts, the assumed mechanism that arrests autoimmunity involves elimination of pathogenic cells and resetting of immune homeostasis. Similar to graft versus tumor (GVT) reactivity, allogeneic transplants are considered to provide a better platform of immunomodulation to induce a graft versus autoimmunity reaction (GVA). It is yet unclear whether recurrence of autoimmunity in both autologous and allogeneic settings reflects relapse of the disease, transplant-associated immune dysfunction or insufficient immune modulation. Possible causes of disease recurrence include reactivation of residual host pathogenic cells and persistence of memory cells, genetic predisposition to autoimmunity and pro-inflammatory characteristics of the target tissues. Most important, there is little evidence that autoimmune disorders are indeed abrogated by current transplant procedures, despite reinstitution of both peripheral and thymic immune homeostasis. It is postulated that non-specific immunosuppressive therapy that precedes and accompanies current bone marrow transplant strategies is detrimental to the active immune process that restores self-tolerance. This proposition refocuses the need to develop strategies of immunomodulation without immunosuppression.

  19. Subretinal transplantation of mouse retinal progenitor cells

    Institute of Scientific and Technical Information of China (English)

    Caihui Jiang; Maonian Zhang; Henry Klassen; Michael Young

    2011-01-01

    The development of cell replacement techniques is promising as a potential treatment for photoreceptor loss. However, the limited integration ability of donor and recipient cells presents a challenge following transplantation. In the present study, retinal progenitor cells (RPCs) were harvested from the neural retinas of enhanced green fluorescent protein mice on postnatal day 1, and expanded in a neurobasal medium supplemented with fetal bovine serum without endothelial growth factor. Using a confocal microscope, immunohistochemistry demonstrated that expanded RPCs in vitro maintain retinal stem cell properties and can be differentiated into photoreceptor cells. Three weeks after transplantation, subretinal transplanted RPCs were found to have migrated and integrated into the outer nuclear layer of recipient retinas with laser injury, some of the integrated cells had differentiated into photoreceptors, and a subpopulation of these cells expressed photoreceptor specific synaptic protein, appearing to form synaptic connections with bipolar cells. These results suggest that subretinal transplantation of RPCs may provide a feasible therapeutic strategy for the loss of retinal photoreceptor cells.

  20. Autologous Stem Cell Transplant for AL Amyloidosis

    Directory of Open Access Journals (Sweden)

    Vivek Roy

    2012-01-01

    Full Text Available AL amyloidosis is caused by clonal plasma cells that produce immunoglobulin light chains which misfold and get deposited as amyloid fibrils. Therapy directed against the plasma cell clone leads to clinical benefit. Melphalan and corticosteroids have been the mainstay of treatment for a number of years and the recent availability of other effective agents (IMiDs and proteasome inhibitors has increased treatment options. Autologous stem cell transplant (ASCT has been used in the treatment of AL amyloidosis for many years. It is associated with high rates of hematologic response and improvement in organ function. However, transplant carries considerable risks. Careful patient selection is important to minimize transplant related morbidity and mortality and ensure optimal patient outcomes. As newer more affective therapies become available the role and timing of ASCT in the overall treatment strategy of AL amyloidosis will need to be continually reassessed.

  1. Advance in hematopoietic stem cells transplantation for leukemia

    Institute of Scientific and Technical Information of China (English)

    HUANG Xiao-jun

    2008-01-01

    @@ During the past 50 years, intensive studies into the characteristics of hematopoietic stem cell transplantation immunology and the emergence of new immunosuppressant and anti-infective drugs have significantly improved the clinical result of hematopoietic stem cell transplantation (HSCT).

  2. Hematopoietic Stem-Cell Transplantation for Sickle Cell Disease

    Directory of Open Access Journals (Sweden)

    Atila Tanyeli

    2014-02-01

    Full Text Available Sickle cell anemia is one of the most common hemoglobinopathies in the worldwide. Sickle cell anemia characterized by crises and organ failure develops over time. Myeloablative stem cell transplantation is curative but it has been performed in children younger than 16 years of age. Modest modifications in the conditioning regimen and supportive care have improved outcome such that the majority of children with a suitable HLA-matched sibling donor can expect a cure from this approach. But nonmyeloablative protocols are crucial for the future of Hematopoietic Stem-Cell Transplantation for older sickle cell anemia patients with organ failure. A protocol for nonmyeloablative allogeneic hematopoietic stem-cell transplantation that includes total-body irradiation and treatment with alemtuzumab and sirolimus can achieve stable, mixed donor–recipient chimerism. Stem cell transplantation is recommended in the presence of HLA-matched siblings in patients at risk.

  3. Bacterial foodborne infections after hematopoietic cell transplantation.

    Science.gov (United States)

    Boyle, Nicole M; Podczervinski, Sara; Jordan, Kim; Stednick, Zach; Butler-Wu, Susan; McMillen, Kerry; Pergam, Steven A

    2014-11-01

    Diarrhea, abdominal pain, and fever are common among patients undergoing hematopoietic cell transplantation (HCT), but such symptoms are also typical with foodborne infections. The burden of disease caused by foodborne infections in patients undergoing HCT is unknown. We sought to describe bacterial foodborne infection incidence after transplantation within a single-center population of HCT recipients. All HCT recipients who underwent transplantation from 2001 through 2011 at the Fred Hutchinson Cancer Research Center in Seattle, Washington were followed for 1 year after transplantation. Data were collected retrospectively using center databases, which include information from transplantation, on-site examinations, outside records, and collected laboratory data. Patients were considered to have a bacterial foodborne infection if Campylobacter jejuni/coli, Listeria monocytogenes, E. coli O157:H7, Salmonella species, Shigella species, Vibrio species, or Yersinia species were isolated in culture within 1 year after transplantation. Nonfoodborne infections with these agents and patients with pre-existing bacterial foodborne infection (within 30 days of transplantation) were excluded from analyses. A total of 12 of 4069 (.3%) patients developed a bacterial foodborne infection within 1 year after transplantation. Patients with infections had a median age at transplantation of 50.5 years (interquartile range [IQR], 35 to 57), and the majority were adults ≥18 years of age (9 of 12 [75%]), male gender (8 of 12 [67%]) and had allogeneic transplantation (8 of 12 [67%]). Infectious episodes occurred at an incidence rate of 1.0 per 100,000 patient-days (95% confidence interval, .5 to 1.7) and at a median of 50.5 days after transplantation (IQR, 26 to 58.5). The most frequent pathogen detected was C. jejuni/coli (5 of 12 [42%]) followed by Yersinia (3 of 12 [25%]), although Salmonella (2 of 12 [17%]) and Listeria (2 of 12 [17%]) showed equal frequencies; no cases of Shigella

  4. [Hemopoietic stem cell transplantation in lymphogranulomatosis].

    Science.gov (United States)

    Uss, A L; Milanovich, N F; Snegir', V M; Skriagin, A E; Zmachinskiĭ, V A; Batan, Z E

    1997-01-01

    Twenty patients with resistant and relapsed Hodgkin's disease were included into this investigation. The treatment effectiveness and regimen-related toxicity of BEAM-protocol were evaluated. Stem cell transplantation (SCT) was carried out either as bone marrow transplantation (BMT) in 11 patients or peripheral blood stem cell transplantation (PBSCT) in 9 patients. A comparison of the results pointed to a significant decrease in neutropenia duration, fewer blood transfusions needed and shorter stay in hospital in the PBSCT group. Complete remission was observed in 90% of patients of the SCT group, 91%-in BMT and 89%-PBSCT groups. It was found that high-dose chemotherapy followed by SCT is more effective in the treatment of resistant and relapsed Hodgkin's disease and, in certain situations, it is a treatment of choice. As to the toxicity of BEAM-protocol, it does not exceed those of the other chemotherapy modalities used in SCT.

  5. [Post-hematopietic stem cell transplant complications].

    Science.gov (United States)

    de Berranger, Eva; Jubert, Charlotte; Michel, Gérard

    2015-01-01

    Under the long-term monitoring of patients treated in childhood or adolescence for cancer, we present in this article the long-term monitoring and therefore possible effects of patients who underwent allergenic hematopoietic stem cell transplantation. This article is based on a collaborative effort organized by the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC), which took place during the 4th day of allograft harmonization practices. Patients affected are children and young adults (0-25 years). We defined the monitoring effects beyond 1 year post-transplant. Our recommendations are based on a literature review, in line with the Leucémie Enfant Adulte (LEA) study cohort of long-term monitoring of patients treated for hematological malignancies in childhood, grafted or not. It became important to determine the nature of problems, their risk factors, frequency and monitoring necessary to implement for their detection. We will not address the therapeutic management of sequelae.

  6. [Hepatic cell transplantation: a new therapy in liver diseases].

    Science.gov (United States)

    Pareja, Eugenia; Cortés, Miriam; Martínez, Amparo; Vila, Juan José; López, Rafael; Montalvá, Eva; Calzado, Angeles; Mir, José

    2010-07-01

    Liver transplantation has been remarkably effective in the treatment in patients with end-stage liver disease. However, disparity between solid-organ supply and increased demand is the greatest limitation, resulting in longer waiting times and increase in mortality of transplant recipients. This situation creates the need to seek alternatives to orthotopic liver transplantation.Hepatocyte transplantation or liver cell transplantation has been proposed as the best method to support patients. The procedure consists of transplanting individual cells to a recipient organ in sufficient quantity to survive and restore the function. The capacity of hepatic regeneration is the biological basis of hepatocyte transplantation. This therapeutic option is an experimental procedure in some patients with inborn errors of metabolism, fulminant hepatic failure and acute and chronic liver failure, as a bridge to orthotopic liver transplantation. In the Hospital La Fe of Valencia, we performed the first hepatocyte transplantation in Spain creating a new research work on transplant program.

  7. Solid organ transplants following hematopoietic stem cell transplant in children.

    Science.gov (United States)

    Bunin, Nancy; Guzikowski, Virginia; Rand, Elizabeth R; Goldfarb, Samuel; Baluarte, Jorge; Meyers, Kevin; Olthoff, Kim M

    2010-12-01

    SOT may be indicated for a select group of pediatric patients who experience permanent organ failure following HSCT. However, there is limited information available about outcomes. We identified eight children at our center who received an SOT following an HSCT. Patients were six months to 18 yr at HSCT. Diseases for which children underwent HSCT included thalassemia, Wiskott-Aldrich syndrome, Shwachman-Diamond/bone marrow failure, sickle cell disease (SCD), erythropoietic porphyria (EP), ALL, chronic granulomatous disease, and neuroblastoma. Time from HSCT to SOT was 13 days to seven yr (median, 27 months. Lung SOT was performed for two patients with BO, kidney transplants for three patients, and liver transplants for three patients (VOD, chronic GVHD). Seven patients are alive with functioning allografts 6-180 months from SOT. Advances in organ procurement, operative technique, immunosuppressant therapy, and infection control may allow SOT for a select group of patients post-HSCT. However, scarcity of donor organs available in a timely fashion continues to be a limiting factor. Children who have undergone HSCT and develop single organ failure should be considered for an SOT if there is a high likelihood of cure of the primary disease.

  8. Hematopoietic stem cell transplantation in multiple sclerosis

    DEFF Research Database (Denmark)

    Rogojan, C; Frederiksen, J L

    2009-01-01

    Intensive immunosuppresion followed by hematopoietic stem cell transplantation (HSCT) has been suggested as potential treatment in severe forms of multiple sclerosis (MS). Since 1995 ca. 400 patients have been treated with HSCT. Stabilization or improvement occurred in almost 70% of cases at least...

  9. Monocyte-Derived Suppressor Cells in Transplantation.

    Science.gov (United States)

    Ochando, Jordi; Conde, Patricia; Bronte, Vincenzo

    Myeloid-derived suppressor cells (MDSC) are cells of myeloid origin with enhanced suppressive function. They are negative regulators of the immune responses and comprise a heterogeneous mixture of immunosuppressive cells of monocytic (M-MDSC) and granulocytic (G-MDSC) origin. A more recent nomenclature proposes the term "suppressive monocyte derived cells" (suppressive MCs) to define CSF1/CSF2-dependent mouse suppressor cells that develop from common monocyte progenitors (cMoPs) after birth. Here, we review the literature about monocytic-derived cells with demonstrated suppressor function in vitro and in vivo within the context of solid organ transplantation.

  10. Limbal stem cell transplantation: current perspectives

    Directory of Open Access Journals (Sweden)

    Atallah MR

    2016-04-01

    Full Text Available Marwan Raymond Atallah, Sotiria Palioura, Victor L Perez, Guillermo Amescua Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA Abstract: Regeneration of the corneal surface after an epithelial insult involves division, migration, and maturation of a specialized group of stem cells located in the limbus. Several insults, both intrinsic and extrinsic, can precipitate destruction of the delicate microenvironment of these cells, resulting in limbal stem cell deficiency (LSCD. In such cases, reepithelialization fails and conjunctival epithelium extends across the limbus, leading to vascularization, persistent epithelial defects, and chronic inflammation. In partial LSCD, conjunctival epitheliectomy, coupled with amniotic membrane transplantation, could be sufficient to restore a healthy surface. In more severe cases and in total LSCD, stem cell transplantation is currently the best curative option. Before any attempts are considered to perform a limbal stem cell transplantation procedure, the ocular surface must be optimized by controlling causative factors and comorbid conditions. These factors include adequate eyelid function or exposure, control of the ocular surface inflammatory status, and a well-lubricated ocular surface. In cases of unilateral LSCD, stem cells can be obtained from the contralateral eye. Newer techniques aim at expanding cells in vitro or in vivo in order to decrease the need for large limbal resection that may jeopardize the “healthy” eye. Patients with bilateral disease can be treated using allogeneic tissue in combination with systemic immunosuppressive therapy. Another emerging option for this subset of patients is the use of noncorneal cells such as mucosal grafts. Finally, the use of keratoprosthesis is reserved for patients who are not candidates for any of the aforementioned options, wherein the choice of the type of keratoprosthesis depends on

  11. Solid organ transplantation after allogeneic hematopoietic stem cell transplantation: a retrospective, multicenter study of the EBMT

    DEFF Research Database (Denmark)

    Koenecke, C; Hertenstein, B; Schetelig, J;

    2010-01-01

    To analyze the outcome of solid organ transplantation (SOT) in patients who had undergone allogeneic hematopoietic stem cell transplantation (HSCT), a questionnaire survey was carried out within 107 European Group of Blood and Marrow Transplantation centers. This study covered HSCT between 1984...

  12. The risk factors of post-transplant lymphoproliferative disorders following haploidentical hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    张春丽

    2014-01-01

    Objective Post-transplant lymphoproliferative disorder(PTLD)occurring after allogeneic hematopoietic stem cell transplantation(allo-HSCT)is rare but severe.Risk factors including pre-HSCT exposure variables,conditioning regimens,transplant-related complications,and post-HSCT immune reconstitution were investigated in the development of PTLD after allo-HSCT.Methods A

  13. Retinal stem cells and potential cell transplantation treatments.

    Science.gov (United States)

    Lin, Tai-Chi; Hsu, Chih-Chien; Chien, Ke-Hung; Hung, Kuo-Hsuan; Peng, Chi-Hsien; Chen, Shih-Jen

    2014-11-01

    The retina, histologically composed of ten delicate layers, is responsible for light perception and relaying electrochemical signals to the secondary neurons and visual cortex. Retinal disease is one of the leading clinical causes of severe vision loss, including age-related macular degeneration, Stargardt's disease, and retinitis pigmentosa. As a result of the discovery of various somatic stem cells, advances in exploring the identities of embryonic stem cells, and the development of induced pluripotent stem cells, cell transplantation treatment for retinal diseases is currently attracting much attention. The sources of stem cells for retinal regeneration include endogenous retinal stem cells (e.g., neuronal stem cells, Müller cells, and retinal stem cells from the ciliary marginal zone) and exogenous stem cells (e.g., bone mesenchymal stem cells, adipose-derived stem cells, embryonic stem cells, and induced pluripotent stem cells). The success of cell transplantation treatment depends mainly on the cell source, the timing of cell harvesting, the protocol of cell induction/transplantation, and the microenvironment of the recipient's retina. This review summarizes the different sources of stem cells for regeneration treatment in retinal diseases and surveys the more recent achievements in animal studies and clinical trials. Future directions and challenges in stem cell transplantation are also discussed.

  14. Cord blood stem cell banking and transplantation.

    Science.gov (United States)

    Dhot, P S; Nair, V; Swarup, D; Sirohi, D; Ganguli, P

    2003-12-01

    Stem cells have the ability to divide for indefinite periods in culture and to give rise to specialized cells. Cord blood as a source of hematopoietic stem cells (HSC) has several advantages as it is easily available, involves non-invasive collection procedure and is better tolerated across the HLA barrier. Since the first cord blood transplant in 1988, over 2500 cord blood HSC transplants have been done world wide. Since then, the advantages of cord blood as a source of hematopietic stem cells for transplantation have become clear. Firstly, the proliferative capacity of HSC in cord blood is superior to that of cells in bone marrow or blood from adults. A 100 ml unit of cord blood contains 1/10th the number of nucleated cells and progenitor cells (CD34+ cells) present in 1000 ml of bone marrow, but because they proliferate rapidly, the stem cell in a single unit of cord blood can reconstitute the entire haematopoietic system. Secondly, the use of cord blood reduces the risk of graft vs host disease. Cord Blood Stem Cell banks have been established in Europe and United States to supply HSC for related and unrelated donors. Currently, more than 65,000 units are available and more than 2500 patients have received transplants of cord blood. Results in children have clearly shown that the number of nucleated cells in the infused cord blood influences the speed of recovery of neutrophils and platelets after myeloablative chemotherapy. The optimal dose is about 2 x 10(7) nucleated cells/kg of body weight. The present study was carried out for collection, separation, enumeration and cryopreservation of cord blood HSC and establishing a Cord Blood HSC Bank. 172 samples of cord blood HSC were collected after delivery of infant prior to expulsion of placenta. The average cord blood volume collected was 101.20 ml. Mononuclear cell count ranged from 7.36 to 25.6 x 10(7)/ml. Viability count of mononuclear cells was 98.1%. After 1 year of cryopreservation, the viability count on

  15. Melatonin improves spermatogonial stem cells transplantation efficiency in azoospermic mice

    Directory of Open Access Journals (Sweden)

    Mohammadreza Gholami

    2014-02-01

    Conclusion: Administration of melatonin (20 mg/kg simultaneously with transplantation of spermatogonial stem cells in azoospermia mouse testis increases the efficiency of transplantation and improves structural properties of the testes tissue.

  16. Haploidentical Hematopoietic Stem-Cell Transplantation in Adults

    Directory of Open Access Journals (Sweden)

    Salem Alshemmari

    2011-01-01

    Full Text Available Haploidentical hematopoietic stem-cell transplantation is an alternative transplant strategy for patients without an HLA-matched donor. Still, only half of patients who might benefit from transplantation are able to find an HLA-matched related or unrelated donor. Haploidentical donor is readily available for many patients in need of immediate stem-cell transplantation. Historical experience with haploidentical stem-cell transplantation has been characterised by a high rejection rate, graft-versus-host disease, and transplant-related mortality. Important advances have been made in this field during the last 20 years. Many drawbacks of haploidentical transplants such as graft failure and significant GVHD have been overcome due to the development of new extensive T cell depletion methods with mega dose stem-cell administration. However, prolonged immune deficiency and an increased relapse rate remain unresolved problems of T cell depletion. New approaches such as partial ex vivo or in vivo alloreactive T cell depletion and posttransplant cell therapy will allow to improve immune reconstitution in haploidentical transplants. Results of unmanipulated stem-cell transplantation with using ATG and combined immunosuppression in mismatched/haploidentical transplant setting are promising. This paper focuses on recent advances in haploidentical hematopoietic stem-cell transplantation for hematologic malignancies.

  17. [Cell transplantation in heart failure management].

    Science.gov (United States)

    Vilquin, Jean-Thomas; Marolleau, Jean-Pierre

    2004-01-01

    Heart failure is becoming a major issue for public health in western countries and the effect of currently available therapies is limited. Therefore cell transplantation was developed as an alternative strategy to improve cardiac structure and function. This review describes the multiple cell types and clinical trials considered for use in this indication. Most studies have been developed in models of post-ischemic heart failure. The transplantation of fetal or neonatal cardiomyocytes has proven to be functionally successful, but ethical as well as immunological and technical reasons make their clinical use limited. Recent reports, however, suggested that adult autologous cardiomyocytes could be prepared from stem cells present in various tissues (bone marrow, vessels, adult heart itself, adipose tissue). Alternatively, endothelial progenitors originating from bone marrow or peripheral blood could promote the neoangiogenesis within the scar tissue. Hematopietic stem cells prepared from bone marrow or peripheral blood have been proposed but their differentiation ability seems limited. Finally, the transplantation of skeletal muscle cells (myoblasts) in the infarcted area improved myocardial function, in correlation with the development of skeletal muscle tissue in various animal models. The latter results paved the way for the development of a first phase I clinical trial of myoblast transplantation in patients with severe post-ischemic heart failure. It required the scale-up of human cell production according to good manufacturing procedures, started in june 2000 in Paris and was terminated in november 2001, and was followed by several others. The results were encouraging and prompted the onset of a blinded, multicentric phase II clinical trial for skeletal muscle cells transplantation. Meanwhile, phase I clinical trials also evaluate the safeness and efficacy of various cell types originating from the bone marrow or the peripheral blood. However, potential side

  18. Regenerative cells for transplantation in hepatic failure.

    Science.gov (United States)

    Ishikawa, Tetsuya; Banas, Agnieszka; Teratani, Takumi; Iwaguro, Hideki; Ochiya, Takahiro

    2012-01-01

    Human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells have an enormous potential; however, their potential clinical application is being arrested due to various limitations such as teratoma formation followed by tumorigenesis, emergent usage, and the quality control of cells, as well as safety issues regarding long-term culture are also delaying their clinical application. In addition, human ES cells have two crucial issues: immunogenicity and ethical issues associated with their clinical application. The efficient generation of human iPS cells requires gene transfer, yet the mechanism underlying pluripotent stem cell induction has not yet been fully elucidated. Otherwise, although human adult regenerative cells including mesenchymal stem cells have a limited capacity for differentiation, they are nevertheless promising candidates for tissue regeneration in a clinical setting. This review highlights the use of regenerative cells for transplantation in hepatic failure.

  19. Undifferentiated spondyloarthritis following allogeneic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Espinoza Luis R

    2010-06-01

    Full Text Available Abstract Background Stem cell transplant has been utilized in the treatment of malignancies and rheumatic disease. Rheumatic disease may be transferred from the donor with active disease or may be developed in a recipient de novo as a late complication of SCT. Case Presentation We here report the rare case of a 26-year old male patient, who has been diagnosed with undifferentiated spondyloarthropathy after unique circumstance. The patient suffered from intermittent inflammatory back pain and peripheral joint swelling for several years and did not find relief through multiple emergency room visits at different medical facilities. After a thorough history and physical exam, it was noted that our patient had developed signs of axial disease along with dactylitis and overall that he had been insidiously developing an undifferentiated spondyloarthopathy after allogeneic stem cell transplantation. Conclusion Our observation supports the hypothesis that de novo rheumatic disease can develop after stem cell transplant for a variety of reasons. Thus, larger studies and awareness of this association are needed to delineate the exact underlying mechanism(s.

  20. Mesenchymal stem cells as feeder cells for pancreatic islet transplants.

    OpenAIRE

    2010-01-01

    Allogeneic islet transplantation serves as a source of insulin-secreting beta-cells for the maintenance of normal glucose levels and treatment of diabetes. However, limited availability of islets, high rates of islet graft failure, and the need for life-long non-specific immunosuppressive therapy are major obstacles to the widespread application of this therapeutic approach. To overcome these problems, pancreatic islet transplantation was recently suggested as a potential target of the "thera...

  1. Cord blood transplants for SCID: better B-cell engraftment?

    Science.gov (United States)

    Chan, Wan-Yin; Roberts, Robert Lloyd; Moore, Theodore B; Stiehm, E Richard

    2013-01-01

    Hematopoietic stem-cell transplantation is the treatment of choice for severe combined immunodeficiency (SCID). Despite successful T-cell engraftment in transplanted patients, B-cell function is not always achieved; up to 58% of patients require immunoglobulin therapy after receiving haploidentical transplants. We report 2 half-sibling males with X-linked γ-chain SCID treated with different sources of stem cells. Sibling 1 was transplanted with T-cell-depleted haploidentical maternal bone marrow and sibling 2 was transplanted with 7/8 human leukocyte antigen-matched unrelated umbilical cord blood. Both patients received pretransplant conditioning and posttransplant graft-versus-host-disease prophylaxis. B-cell engraftment and function was achieved in sibling 1 but not in sibling 2. This disparate result is consistent with a review of 19 other SCID children who received cord blood transplants. B-cell function, as indicated by no need for immunoglobulin therapy, was restored in 42% of patients given haploidentical transplants and in 68% of patients given matched unrelated donor transplants compared with 80% of patients given cord blood transplants. Cord blood is an alternative source of stem cells for transplantation in children with SCID and has a higher likelihood of B-cell reconstitution.

  2. Cryptococcal meningitis post autologous stem cell transplantation.

    Science.gov (United States)

    Chaaban, S; Wheat, L J; Assi, M

    2014-06-01

    Disseminated Cryptococcus disease occurs in patients with defective T-cell immunity. Cryptococcal meningitis following autologous stem cell transplant (SCT) has been described previously in only 1 patient, 4 months post SCT and while off antifungal prophylaxis. We present a unique case of Cryptococcus meningitis pre-engraftment after autologous SCT, while the patient was receiving fluconazole prophylaxis. A 41-year-old man with non-Hodgkin's lymphoma underwent autologous SCT. Post-transplant prophylaxis consisted of fluconazole 400 mg daily, levofloxacin 500 mg daily, and acyclovir 800 mg twice daily. On day 9 post transplant, he developed fever and headache. Peripheral white blood cell count (WBC) was 700/μL. Magnetic resonance imaging of the brain showed lesions consistent with meningoencephalitis. Cerebrospinal fluid (CSF) analysis revealed a WBC of 39 with 77% lymphocytes, protein 63, glucose 38, CSF pressure 20.5 cmH2 O, and a positive cryptococcal antigen. CSF culture confirmed Cryptococcus neoformans. The patient was treated with liposomal amphotericin B 5 mg/kg intravenously daily, and flucytosine 37.5 mg/kg orally every 6 h. He was switched to fluconazole 400 mg daily after 3 weeks of amphotericin therapy, with sterilization of the CSF with negative CSFCryptococcus antigen and negative CSF culture. Review of the literature revealed 9 cases of cryptococcal disease in recipients of SCT. Median time of onset was 64 days post transplant. Only 3 meningitis cases were described; 2 of them after allogeneic SCT. Fungal prophylaxis with fluconazole post autologous SCT is recommended at least through engraftment, and for up to 100 days in high-risk patients. A high index of suspicion is needed to diagnose and treat opportunistic infections, especially in the face of immunosuppression and despite adequate prophylaxis. Infection is usually fatal without treatment, thus prompt diagnosis and therapy might be life saving.

  3. CMV IN HEMATOPOIETIC STEM CELL TRANSPLANTATION

    Directory of Open Access Journals (Sweden)

    Rafael de la Camara

    2016-06-01

    Full Text Available Due to its negative impact in the outcome of stem cell transplant (SCT and solid organ transplant patients (SOT CMV has been called “the troll of transplantation”. One of the greatest advances in the management of SCT has been the introduction of the preemptive strategy. Since its introduction, the incidence of the viremia, as expected, remains unchanged but there has been a marked decline in the incidence of early CMV disease. But in spite of the advances in prevention of CMV disease, CMV is still today an important cause of morbidity and mortality. Late CMV disease is still occurring in a significant proportion of patients and the so-called indirect effects of CMV are causing significant morbidity and mortality. Fortunately, there have been several advances in the development of new antivirals, adoptive immunotherapy and DNA-CMV vaccines that might transform the management of CMV in the near future.

  4. Use of hematopoietic cell transplants to achieve tolerance in patients with solid organ transplants.

    Science.gov (United States)

    Strober, Samuel

    2016-03-24

    The goals of tolerance in patients with solid organ transplants are to eliminate the lifelong need for immunosuppressive (IS) drugs and to prevent graft loss due to rejection or drug toxicity. Tolerance with complete withdrawal of IS drugs has been achieved in recipients of HLA-matched and mismatched living donor kidney transplants in 3 medical centers using hematopoietic cell transplants to establish mixed or complete chimerism.

  5. Allogeneic hematopoietic stem cell transplantation: transfusion issues

    Directory of Open Access Journals (Sweden)

    Akkök ÇA

    2016-05-01

    Full Text Available Çiğdem Akalın Akkök,1,21Department of Immunology and Transfusion Medicine, Oslo University Hospital, Ullevaal, Oslo, Norway; 2Department of Clinical Immunology and Transfusion Medicine, Lund University Hospital, Lund, Sweden Abstract: Allogeneic hematopoietic stem cell transplantation (AHSCT is an intention-to-cure treatment strategy in several malignancies and nonmalignancies. The number of patients receiving AHSCT is increasing due to new indications, and more elderly patients with comorbidities are included in the protocols. Survival of the patients undergoing AHSCT has improved owing to better patient care, including optimization of transfusion support, which has a major contribution. However, transfusion can also be hazardous. Increasing awareness about transfusion and finding the balance between avoiding unnecessary transfusions and transfusing the correct component when needed are the key issues. Myeloablative conditioning results in pancytopenia, and the patients are prone to infections, anemia, and bleeding both before and after transplantation. Until red cell and platelet engraftment, the patients are usually transfusion dependent needing red cell and/or platelet components. Physicians dealing with AHSCT patients should be well informed about the attributes of the blood components they order. Knowledge about transfusion indications, triggers, and how to prevent and manage eventual transfusion complications is also required. The clinical picture can be challenging, and transplantation/treatment-related toxicity/complications can sometimes be difficult to distinguish from a transfusion complication, especially if the latter one took place, for instance, several days or weeks ago. ABO compatibility between the patient and the donor is not a prerequisite when choosing human leukocyte antigen-matched hematopoietic stem cell donor. Consequently, ABO incompatibility exists in ~40% of the cases and brings some immunohematological issues

  6. Leukemia in donor cells after allogeneic hematopoietic stem cell transplant

    OpenAIRE

    2002-01-01

    The development of leukemia in donor cells after allogeneic hematopoietic stem cell transplant is an extremely rare event. We report here the case of a patient who developed myelodysplastic syndrome/acute myeloid leukemia, in cells of donor origin 3.5 years after related donor HSCT for refractory chronic lymphocytic leukemia and therapy-induced myelodysplastic syndrome. The origin of the leukemia was determined by analysis of minisatillite polymorphism tested on CD34(+) cells.

  7. Salvage Second Hematopoietic Cell Transplantation in Myeloma

    Science.gov (United States)

    Michaelis, Laura C.; Saad, Ayman; Zhong, Xiaobo; Le-Rademacher, Jennifer; Freytes, Cesar O.; Marks, David I.; Lazarus, Hillard M.; Bird, Jennifer M.; Holmberg, Leona; Kamble, Rammurti T.; Kumar, Shaji; Lill, Michael; Meehan, Kenneth R.; Saber, Wael; Schriber, Jeffrey; Tay, Jason; Vogl, Dan T.; Wirk, Baldeep; Savani, Bipin N.; Gale, Robert P.; Vesole, David H.; Schiller, Gary J.; Abidi, Muneer; Anderson, Kenneth C.; Nishihori, Taiga; Kalaycio, Matt E.; Vose, Julie M.; Moreb, Jan S.; Drobyski, William; Munker, Reinhold; Roy, Vivek; Ghobadi, Armin; Holland, H. Kent; Nath, Rajneesh; To, L. Bik; Maiolino, Angelo; Kassim, Adetola A.; Giralt, Sergio A.; Landau, Heather; Schouten, Harry C.; Maziarz, Richard T.; Mikhael, Joseph; Kindwall-Keller, Tamila; Stiff, Patrick J.; Gibson, John; Lonial, Sagar; Krishnan, Amrita; Dispenzieri, Angela; Hari, Parameswaran

    2013-01-01

    Autologous hematopoietic cell transplantation (AHCT) as initial therapy of patients with multiple myeloma (MM) improves survival. However, data to support this approach for relapsed/progressive disease after initial AHCT (AHCT1) are limited. Using Center for International Blood and Marrow Transplant Research data, we report the outcomes of 187 patients who underwent a second AHCT (AHCT2) for the treatment of relapsed/progressive MM. Planned tandem AHCT was excluded. Median age at AHCT2 was 59 years (range, 28 to 72), and median patient follow-up was 47 months (range, 3 to 97). Nonrelapse mortality after AHCT2 was 2% at 1 year and 4% at 3 years. Median interval from AHCT1 to relapse/progression was 18 months, and median interval between transplantations was 32 months. After AHCT2, the incidence of relapse/progression at 1 and 3 years was 51% and 82%, respectively. At 3 years after AHCT2, progression-free survival was 13%, and overall survival was 46%. In multivariate analyses, those relapsing ≥36 months after AHCT1 had superior progression-free (P = .045) and overall survival (P = .019). Patients who underwent AHCT2 after 2004 had superior survival (P = .026). AHCT2 is safe and feasible for disease progression after AHCT1. In this retrospective study, individuals relapsing ≥36 months from AHCT1 derived greater benefit from AHCT2 compared with those with a shorter disease-free interval. Storage of an adequate graft before AHCT1 will ensure that the option of a second autologous transplantation is retained for patients with relapsed/progressive MM. PMID:23298856

  8. T-cell-replete haploidentical transplantation versus autologous stem cell transplantation in adult acute leukemia: a matched pair analysis.

    Science.gov (United States)

    Gorin, Norbert-Claude; Labopin, Myriam; Piemontese, Simona; Arcese, William; Santarone, Stella; Huang, He; Meloni, Giovanna; Ferrara, Felicetto; Beelen, Dietrich; Sanz, Miguel; Bacigalupo, Andrea; Ciceri, Fabio; Mailhol, Audrey; Nagler, Arnon; Mohty, Mohamad

    2015-04-01

    Adult patients with acute leukemia in need of a transplant but without a genoidentical donor are usually considered upfront for transplantation with stem cells from any other allogeneic source, rather than autologous stem cell transplantation. We used data from the European Society for Blood and Marrow Transplantation and performed a matched pair analysis on 188 T-cell-replete haploidentical and 356 autologous transplants done from January 2007 to December 2012, using age, diagnosis, disease status, cytogenetics, and interval from diagnosis to transplant as matching factors. "Haploidentical expert" centers were defined as having reported more than five haploidentical transplants for acute leukemia (median value for the study period). The median follow-up was 28 months. Multivariate analyses, including type of transplant categorized into three classes ("haploidentical regular", "haploidentical expert" and autologous), conditioning intensity (reduced intensity versus myeloablative conditioning) and the random effect taking into account associations related to matching, showed that non-relapse mortality was higher following haploidentical transplants in expert (HR: 4.7; P=0.00004) and regular (HR: 8.98; Ptransplants was lower in expert centers (HR:0.39; P=0.0003) but in regular centers was similar to that for autologous transplants. Leukemia-free survival and overall survival rates were higher following autologous transplantation than haploidentical transplants in regular centers (HR: 1.63; P=0.008 and HR: 2.31; P=0.0002 respectively) but similar to those following haploidentical transplants in expert centers. We conclude that autologous stem cell transplantation should presently be considered as a possible alternative to haploidentical transplantation in regular centers that have not developed a specific expert program.

  9. Tuberculosis in Hematopoietic Stem Cell Transplant Recipients

    OpenAIRE

    Ramos, Jéssica Fernandes; Batista, Marjorie Vieira; Costa, Silvia Figueiredo

    2013-01-01

    Literature on tuberculosis (TB) occurring in recipients of Hematopoietic Stem Cell Transplant (HSCT) is scanty even in countries where TB is common. Most reports of TB in HSCT patients were from ASIA, in fact the TB incidence ranging from 0.0014 (USA) to 16% (Pakistan). There are few reports of TB diagnosis during the first two weeks after HSCT; most of cases described in the literature occurred after 90 days of HSCT, and the lung was the organ most involved. The mortality ranged from 0 to 50...

  10. IN UTERO HAEMATOPOIETIC STEM CELL TRANSPLANTATION (IUHSCT

    Directory of Open Access Journals (Sweden)

    Maria Concetta Renda

    2009-12-01

    Among 46 cases of  IUHSCT reported in humans, successful engraftment  was obtained only in cases of  X-SCID. Useful levels of chimerism has not been achieved in non-immunodeficiency diseases, and  a detectable engrafment , was  reported only in one case  of  ß-thalassemia transplanted at 12 weeks of gestation  by fetal liver cells  In one a-thalassemia case, where a-globin-dependent hemoglobin production and anemia are present during fetal period, microchimerism  and tolerance were suggested . To overcome the IUHSCT engraftment barriers , it is necessary to develop strategies to improve the competitive capacity of donor cells and  to define the gestational age of the possible immunological “window of opportunity” in the human fetus. In utero haematopoietic stem cell transplantation (IUHSCT is a non-myeloablative promising approach for the prenatal treatment of a variety of genetic disorders and  could be an alternative  option to therapeutical abortion in some congenital diseases like haematological hereditary  syndromes.

  11. Stem cell biology and cell transplantation therapy in the retina.

    Science.gov (United States)

    Osakada, Fumitaka; Hirami, Yasuhiko; Takahashi, Masayo

    2010-01-01

    Embryonic stem (ES) cells, which are derived from the inner cell mass of mammalian blastocyst stage embryos, have the ability to differentiate into any cell type in the body and to grow indefinitely while maintaining pluripotency. During development, cells undergo progressive and irreversible differentiation into specialized adult cell types. Remarkably, in spite of this restriction in potential, adult somatic cells can be reprogrammed and returned to the naive state of pluripotency found in the early embryo simply by forcing expression of a defined set of transcription factors. These induced pluripotent stem (iPS) cells are molecularly and functionally equivalent to ES cells and provide powerful in vitro models for development, disease, and drug screening, as well as material for cell replacement therapy. Since functional impairment results from cell loss in most central nervous system (CNS) diseases, recovery of lost cells is an important treatment strategy. Although adult neurogenesis occurs in restricted regions, the CNS has poor potential for regeneration to compensate for cell loss. Thus, cell transplantation into damaged or diseased CNS tissues is a promising approach to treating various neurodegenerative disorders. Transplantation of photoreceptors or retinal pigment epithelium cells derived from human ES cells can restore some visual function. Patient-specific iPS cells may lead to customized cell therapy. However, regeneration of retinal function will require a detailed understanding of eye development, visual system circuitry, and retinal degeneration pathology. Here, we review the current progress in retinal regeneration, focusing on the therapeutic potential of pluripotent stem cells.

  12. Arrhythmias in the setting of hematopoietic cell transplants.

    Science.gov (United States)

    Tonorezos, E S; Stillwell, E E; Calloway, J J; Glew, T; Wessler, J D; Rebolledo, B J; Pham, A; Steingart, R M; Lazarus, H; Gale, R P; Jakubowski, A A; Schaffer, W L

    2015-09-01

    Prior studies report that 9-27% of persons receiving a hematopoietic cell transplant develop arrhythmias, but the effect on outcomes is largely unknown. We reviewed data from 1177 consecutive patients ⩾40 years old receiving a hematopoietic cell transplant at one center during 1999-2009. Transplant indication was predominately leukemia, lymphoma and multiple myeloma. Overall, 104 patients were found to have clinically significant arrhythmia: 43 before and 61 after transplant. Post-transplant arrhythmias were most frequently atrial fibrillation (N=30), atrial flutter (N=7) and supraventricular tachycardia (N=11). Subjects with an arrhythmia post transplant were more likely to have longer median hospital stays (32 days vs 23, P=transplant (41% vs 15%; Ptransplant, diagnosis, history of pretransplant arrhythmia, and transplant-related variables, post-transplant arrhythmia was associated with a greater risk for death within a year of transplant (odds ratio 3.5, 95% confidence interval: 2.1, 5.9; Ptransplants are associated with significant morbidity and mortality. A prospective study of arrhythmia in the transplant setting is warranted.

  13. Effects of Dermal Multipotent Cell Transplantation on Skin Wound Healing

    Institute of Scientific and Technical Information of China (English)

    ShiChunmeng; ChengTianmin; SuYongping; RanXinze; MaiYue; QuJifu; LouShufen; XuHui; LuoChengji

    2005-01-01

    There is increasing evidence that dermis contains adult multipotent stem cells. To investigate the effects of dermis-derived multipotent cells on wound healing, we transplanted a clonal population of dermis-derived multipotent cells (termed as DMCs) by topical and systemic application into the skin wound of rats with simple wounds and rats with combined wound and radiation injury. Our results suggest that both topical and systemic transplantation of DMCs accelerate the healing process in rats with a simple wound; the promoting effect by topical transplantation occurs earlier than systemic transplantation. However, systemic transplantation of DMCs promotes the healing process in irradiated rats, while topical transplantation of DMCs fails. Further studies on the mechanisms of DMCs to promote wound healing indicate that the supernatant of DMCs could promote the proliferation of fibroblasts and epidermal cells; DMCs expressed transcripts of a serics of cytokincs and cxtraccllular matrix molecules, including VEGF, PDGF, HGF, TGF-β, ICAM-1, VCAM-1, and Fibronectin, which were closely related to the wound healing by DNA microarray analysis. The implanted DMCs can engraft into recipient skin wounded tissues after transplantation by the FISH analysis with Y-chromosome-specific probe. Systemic transplantation of DMCs also promotes the recovery of peripheral white blood cells in irradiated rats. These results demonstrate the different effects of DMCs on wound healing in nonirradiated and irradiated rats and illustrate the importance of optimizing wound healing via the topical or systemic transplantation of stem cells.

  14. The Use of Statins in Hematopoietic Stem Cell Transplantation and Solid Organ Transplantation.

    Science.gov (United States)

    Shimabukuro-Vornhagen, Alexander; Schlösser, Hans; Kisner, Tulay; Stippel, Dirk L; von Bergwelt-Baildon, Michael

    2013-01-14

    Allogeneic hematopoietic stem cell transplantation and solid organ transplantation have become established treatments offered to patients for whom there are otherwise no curative treatment options. Unfortunately, these therapeutic modalities are associated with severe complications that limit its applicability. Alloimmunity is an important cause of morbidity and mortality after both organ transplantation and allogeneic hematopoietic stem cell transplantation and represents a major barrier to the more wide-spread use of these treatment modalities. Statins are a class of lipid-lowering drugs, which also posses immunomodulatory effects. Results from preclinial research and early-stage clinical studies indicate that treatment with statins could be beneficial for the prevention and treatment of graft-versus-host disease and transplant rejection. In addition to preventing graft-versus-host disease or graft rejection statins possess several other effects that might prove beneficial in the setting of transplantation, such as cardiovascular protection and antineoplastic activity. Here we summarize the current knowledge about the immunomodulatory effects of statins and discuss the clinical implications for their use in patients undergoing stem cell transplantation or solid organ transplantation.

  15. Gastrointestinal and hepatic complications of hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    Hande H Tuncer; Naveed Rana; Cannon Milani; Angela Darko; Samer A Al-Homsi

    2012-01-01

    Recognition and management of gastrointestinal and hepatic complications of hematopoietic stem cell transplantation has gained increasing importance as indications and techniques of transplantation have expanded in the last few years.The transplant recipient is at risk for several complications including conditioning chemotherapy related toxicities,infections,bleeding,sinusoidal obstruction syndrome,acute and chronic graftversus-host disease (GVHD) as well as other long-term problems.The severity and the incidence of many complications have improved in the past several years as the intensity of conditioning regimens has diminished and better supportive care and GVHD prevention strategies have been implemented.Transplant clinicians,however,continue to be challenged with problems arising from human leukocyte antigen-mismatched and unrelated donor transplants,expanding transplant indications and age-limit.This review describes the most commonly seen transplant related complications,focusing on their pathogenesis,differential diagnosis and management.

  16. Primary Immunodeficiency Diseases and Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Ayse Ozkan

    2014-02-01

    Full Text Available Hematopoietic stem cell transplantation (HSCT is the only curative therapy for primary immunodeficiency diseases. Early diagnosis, including prenatally, and early transplantation improve HSCT outcomes. Survival rates improve with advances in the methods of preparing hosts and donor cells, and in supportive and conditioning regimes.

  17. Advances in mammalian spermatogonial stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xueming; LI Dexue; YUE Zhanpeng; LI Lingling; YU Jiaao

    2004-01-01

    Spermatogonial stem cell (SSC) transplantation is a novel technique by which testicular cells from normal, transgenic or mutant donor are introduced into the seminiferous tubules of recipient testes through microinjection. Subsequently, donor SSCs survive,migrate, anchor and proliferate in the recipient testis, furthermore, initiate spermatogenesis and even produce sperms capable of fertilization. This technique provides a new approach for the researches of spermatogenesis mechanism, regeneration of spermatogenesis in sterile individuals and reproduction of transgenic animals. This review focuses on the methodological breakthroughs and highlights the recent findings that have substantially increased understanding of SSC biology. The article provides a comprehensive overview of this technique and its multiple applications in basic science and medicine. And the perspective direction of this field in the near future is proposed.

  18. Fetal stem cell transplantation: Past, present, and future.

    Science.gov (United States)

    Ishii, Tetsuya; Eto, Koji

    2014-09-26

    Since 1928, human fetal tissues and stem cells have been used worldwide to treat various conditions. Although the transplantation of the fetal midbrain substantia nigra and dopaminergic neurons in patients suffering from Parkinson's disease is particularly noteworthy, the history of other types of grafts, such as those of the fetal liver, thymus, and pancreas, should be addressed as there are many lessons to be learnt for future stem cell transplantation. This report describes previous practices and complications that led to current clinical trials of isolated fetal stem cells and embryonic stem (ES) cells. Moreover, strategies for transplantation are considered, with a particular focus on donor cells, cell processing, and the therapeutic cell niche, in addition to ethical issues associated with fetal origin. With the advent of autologous induced pluripotent stem cells and ES cells, clinical dependence on fetal transplantation is expected to gradually decline due to lasting ethical controversies, despite landmark achievements.

  19. Fetal stem cell transplantation: Past, present, and future

    Institute of Scientific and Technical Information of China (English)

    Tetsuya; Ishii; Koji; Eto

    2014-01-01

    Since 1928, human fetal tissues and stem cells have been used worldwide to treat various conditions. Although the transplantation of the fetal midbrain substantia nigra and dopaminergic neurons in patients suffering from Parkinson’s disease is particularly noteworthy, the history of other types of grafts, such as those of the fetal liver, thymus, and pancreas, should be addressed as there are many lessons to be learnt for future stem cell transplantation. This report describes previous practices and complications that led to current clinical trials of isolated fetal stem cells and embryonic stem(ES) cells. Moreover, strategies for transplantation are considered, with a particular focus on donor cells, cell processing, and the therapeutic cell niche, in addition to ethical issues associated with fetal origin. With the advent of autologous induced pluripotent stem cells and ES cells, clinical dependence on fetal transplantation is expected to gradually decline due to lasting ethical controversies, despite landmark achievements.

  20. 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%.

  1. Stem Cells Transplanted in Monkeys without Anti-Rejection Drugs

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_160989.html Stem Cells Transplanted in Monkeys Without Anti-Rejection Drugs Scientists say goal is to create banks of stem cells that could be used for any human patient ...

  2. Cytomegalovirus (CMV) Infection: A Guide for Patients and Families After Stem Cell Transplant

    Science.gov (United States)

    ... Infection: A Guide for Patients and Families after Stem Cell Transplant What is cytomegalovirus (CMV)? Cytomegalovirus (CMV), a ... weakened by medicines that you must take after stem cell transplant and by the transplant itself. Your body ...

  3. Solid organ transplantation after allogeneic hematopoietic stem cell transplantation: a retrospective, multicenter study of the EBMT

    DEFF Research Database (Denmark)

    Koenecke, C; Hertenstein, B; Schetelig, J

    2010-01-01

    To analyze the outcome of solid organ transplantation (SOT) in patients who had undergone allogeneic hematopoietic stem cell transplantation (HSCT), a questionnaire survey was carried out within 107 European Group of Blood and Marrow Transplantation centers. This study covered HSCT between 1984...... and 2007 in Europe. Forty-five SOT in 40 patients were reported. Fifteen liver, 15 renal, 13 lung, 1 heart and 1 skin transplantations were performed in 28 centers. Overall survival (OS) of patients after SOT was 78% at 5 years (95% confidence interval [CI], 64% to 92%). OS at 5 years was 100% for renal......, 71% (95% CI, 46% to 96%) for liver and 63% (95% CI, 23% to 100%) for lung transplant recipients. The 2-year-incidence of SOT failure was 20% (95% CI, 4% to 36%) in patients with graft-versus-host disease (GvHD) and 7% (95% CI, 0% to 21%) in patients without GvHD before SOT. The relapse incidence...

  4. The Neuropsychiatry of Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Mitchell R. Levy

    2006-06-01

    Full Text Available BACKGROUND AND OBJECTIVES: Regimens incorporating hematopoietic stem cell transplantation (HSCT have become widely utilized in disease treatments, particularly for cancer. These complex treatment programs also expose patients to central nervous system (CNS toxicities from chemotherapy, irradiation, infection, metabolic effects and immunosuppression. METHODS: Relevant recent medical literature from Medline and bibliographies in pertinent publications are reviewed with a focus on those cases and studies pertaining to neuropsychiatric effects of HSCT. RESULTS: High rates of neuropsychiatric sequelae occur on a continuum from acute to chronic. Adverse outcomes include focal CNS deficits and severe global manifestations such as seizures, encephalopathy and delirium. More graduated effects on cognition, energy and mood are frequently seen, impacting patient function. CONCLUSIONS: Additional research on neuropsychiatric outcomes and treatment interventions is needed in the HSCT setting. Risks for neuropsychiatric deficits should be part of an ongoing informed consent discussion among treating physicians, patients and families.

  5. Resistant bacteria in stem cell transplant recipients

    Directory of Open Access Journals (Sweden)

    Nucci Marcio

    2002-01-01

    Full Text Available Bacterial infections account for most infections in hematopoietic stem cell transplant recipients. While early mortality reduced dramatically with the introduction of the concept of empirical antibiotic therapy in neutropenic patients, no effect of prophylaxis on the mortality was observed in many studies. On the other hand, antibiotic prophylaxis has resulted in the emergence of resistance among bacteria. In addition, the choice of the antibiotic regimen for empirical therapy and the practices of antibiotic therapy during neutropenia may result in a significant shift in the pattern of bacterial infections. The use of quinolones and vancomycin as prophylaxis, and of carbapenems and vancomycin in the empirical antibiotic therapy, are associated with the appearance of resistant Gram-positive and Gram-negative bacteria. Therefore, hematologists must be aware of the impact of these practices on the emergence of infections due to multi-resistant pathogens, since these infections may be associated with increased mortality.

  6. ROLE OF HEMATOPOIETIC STEM CELL TRANSPLANTATION

    Directory of Open Access Journals (Sweden)

    Angelo Michele Carella

    2012-10-01

    Full Text Available Hodgkin lymphoma is one of the most curable human tumors. Despite this, about 30% of these patients relapsed or are primary refractory to the first line treatment. Autografting is generally considered the standard of care for these patients. Alternative salvage strategies have been evaluated such as high dose sequential and tandem autografting strategies. In younger patients,  refractory or early relapsed after autografting, allogeneic stem cell transplantation has been employed but this approach has been followed by significant concerns since the treatment related mortality often exceeded 40-50%, and relapses were not uncommon. It is clear that patient selection remains an issue in all allografting reports. At the end, new drugs and novel treatment strategies, that are based on our understanding of the disease biology and signaling pathways, are needed to improve treatment outcome for these patients. The two leading compounds Brentuximab Vedotin and Panobinostat, are currently under evaluation  in several clinical trials.

  7. Immunosuppressive T-cell antibody induction for heart transplant recipients

    DEFF Research Database (Denmark)

    Penninga, Luit; Møller, Christian H; Gustafsson, Finn

    2013-01-01

    Heart transplantation has become a valuable and well-accepted treatment option for end-stage heart failure. Rejection of the transplanted heart by the recipient's body is a risk to the success of the procedure, and life-long immunosuppression is necessary to avoid this. Clear evidence is required...... to identify the best, safest and most effective immunosuppressive treatment strategy for heart transplant recipients. To date, there is no consensus on the use of immunosuppressive antibodies against T-cells for induction after heart transplantation....

  8. Individualization of drug exposure in pediatric hematopoietic stem cell transplantation

    NARCIS (Netherlands)

    Bartelink, I.H.

    2012-01-01

    Allogeneic haematopoeitic stem cell transplantation is a potentially curative treatment for a variety of diseases. Its use is limited by 1) the risk of graft failures and relapse of malignant diseases, 2) transplantation-associated complications, and 3) late effects. There is a large and largely unp

  9. Antifungal prophylaxis in stem cell transplantation centers in Turkey

    Directory of Open Access Journals (Sweden)

    Hamdi Akan

    2011-12-01

    Full Text Available Objective: This study aimed to determine the current state of antifungal prophylaxis in Turkish stem cell transplantation (SCT centers. Materials and Methods: The were 38 active stem cell transplantation centers in Turkey, 28 of which were registered with the European Group for Blood and Marrow Transplantation (EBMT. Survey questionnaires were sent to the 28 EBMT centers in an effort to collect data on antifungal prophylaxis in different settings. In all, 24 of the centers completed the survey; 1 of the 24 centers was excluded from the study, as it was under construction at the time and was not performing transplantation.Results: In all, 15 (65% of the 23 centers were adult SCT centers, 7 (31% were pediatric SCT centers, and 1 center treated both adult and pediatric patients. All centers (23/23 performed both allogeneic and autologous transplants, 20 centers performed non-myeloablative transplants, 8 performed cord blood transplants, and 7 performed unrelated transplants. Primary antifungal prophylaxis was used at all 23 centers during allogeneic transplants, whereas 18 of the 23 centers used it during every autologous transplant and 2 of the 23 centers used it during autologous transplants on a per case basis. The most common drug used for prophylaxis was fluconazole (F (21/23, followed by itraconazole (I (3/23, amphotericin-B (2/23, and posaconazole (1/23. Among the 23 centers, 3 reported that for allogenic transplants they changed the antifungal prophylactic in cases of graft versus host disease (GVHD, and 12 of the 23 centers reported that they changed the antifungal prophylactic in case of nearby construction. All 23 centers performed secondary prophylaxis. Conclusion: Antifungal prophylaxis for hematopoetic SCT patients was the standard protocol in the 23 centers included in the study, usually with such azoles as F. The introduction of posaconazole in Turkey and the potential approval of voriconazole for antifungal prophylaxis will

  10. Bilateral olfactory ensheathing cell transplantation promotes neurological function in a rat model of cerebral infarction

    Institute of Scientific and Technical Information of China (English)

    Zhihua Yang; Wenli Sheng; Huiyong Shen; Qinghua Hou; Rui Li; Jinsheng Zeng; Ruxun Huang

    2011-01-01

    In the present study, olfactory ensheathing cells were transplanted into the cortices of infarcted (infarct transplantation group), normal (normal transplantation group), and bilateral hemispheres (bilateral transplantation group). Olfactory ensheathing cells migrated to the infarct focus. The number of growth associated protein 43-positive cells and nerve fibers was slightly increased in the infarct area. These changes were more evident in the bilateral cortical transplantation group. Results demonstrated that transplanted olfactory ensheathing cells can migrate in rats with cerebral infarction. The olfactory ensheathing cells on the normal side can also promote neurological function. Bilateral cortical transplantation exhibited superior effects over unilateral transplantation.

  11. Antifungal Treatment in Stem Cell Transplantation Centers in Turkey.

    Science.gov (United States)

    Akan, Hamdi; Atilla, Erden

    2016-03-05

    Despite the development of various guidelines, the approach to antifungal treatment in stem cell transplantation centers differs according to country or even between centers. This led to the development of another survey that aims to understand the antifungal treatment policies of Turkish stem cell transplantation centers. Although there has been an increasing trend towards the use of diagnostic-based treatments in Turkey in the last few years, empirical treatment is still the main approach. The practices of the stem cell transplantation centers reflect the general trends and controversies in this area, while there is a considerable use of antifungal combination therapy.

  12. First Successful Haploidentical Stem Cell Transplantation in Romania.

    Science.gov (United States)

    Tănase, Alina; Tomuleasa, C; Mărculescu, Alexandra; Bardaş, A; Coliţă, Anca; Ciurea, Ş O

    2016-09-01

    Hematopoietic stem cell transplantation is an established treatment for many malignant and non-malignant haematological disorders. In the current case report, we describe the first haploidentical stem cell transplantation, used for the first time in Romania, the case of a 33 year-old young woman diagnosed with Hodgkin's lymphoma that has underwent a haploSCT after she relapsed from several chemotherapy regimens, as well as after an autologous stem cell transplantation. This success represents a prèmiere in Romanian clinical hematology, being the first case of a haploSCT in Romania, as well as in South-Eastern Europe.

  13. [Monomorphic post-transplant T-lymphoproliferative disorder after autologous stem cell transplantation for multiple myeloma].

    Science.gov (United States)

    Ishikawa, Tetsuya; Shimizu, Hiroaki; Takei, Toshifumi; Koya, Hiroko; Iriuchishima, Hirono; Hosiho, Takumi; Hirato, Junko; Kojima, Masaru; Handa, Hiroshi; Nojima, Yoshihisa; Murakami, Hirokazu

    2016-01-01

    We report a rare case of T cell type monomorphic post-transplant lymphoproliferative disorders (PTLD) after autologous stem cell transplantation. A 53-year-old man with multiple myeloma received autologous stem cell transplantation and achieved a very good partial response. Nine months later, he developed a high fever and consciousness disturbance, and had multiple swollen lymph nodes and a high titer of Epstein-Barr (EB) virus DNA in his peripheral blood. Neither CT nor MRI of the brain revealed any abnormalities. Cerebrospinal fluid contained no malignant cells, but the EB virus DNA titer was high. Lymph node biopsy revealed T cell type monomorphic PTLD. Soon after high-dose treatment with methotrexate and cytosine arabinoside, the high fever and consciousness disturbance subsided, and the lymph node swelling and EB virus DNA disappeared. Given the efficacy of chemotherapy in this case, we concluded that the consciousness disturbance had been induced by central nervous system involvement of monomorphic PTLD.

  14. Prenatal transplantation of mesenchymal stem cells to treat osteogenesis imperfecta.

    Directory of Open Access Journals (Sweden)

    Jerry KY Chan

    2014-10-01

    Full Text Available Osteogenesis Imperfecta (OI can be a severe disorder that can be diagnosed before birth. Transplantation of mesenchymal stem cells (MSC has the potential to improve the bone structure, growth and fracture healing. In this review we give an introduction to OI and MSC, and the basis for prenatal and postnatal transplantation in OI. We also summarize the two patients with OI who has received prenatal and postnatal transplantation of MSC.The findings suggest that prenatal transplantation of allogeneic MSC in OI is safe. The cell therapy is of likely clinical benefit with improved linear growth, mobility and reduced fracture incidence. Unfortunately, the effect is transient. For this reason postnatal booster infusions using same-donor MSC have been performed with clinical benefit, and without any adverse events.So far there is limited experience in this specific field and proper studies are required to accurately conclude on clinical benefits of MSC transplantation to treat OI.

  15. Autologous stem cell transplantation versus alternative allogeneic donor transplants in adult acute leukemias.

    Science.gov (United States)

    Claude Gorin, Norbert

    2016-04-01

    The availability of alternative sources of stem cells including most recently T-replete haploidentical marrow or peripheral blood, and the increasing use of reduced-intensity conditioning (RIC), renders feasible an allogeneic transplant to almost all patients with acute leukemia up to 70 years of age. Autologous stem cell transplantation (ASCT) for consolidation of complete remission (CR), however, offers in some circumstances an alternative option. Although associated with a higher relapse rate, autologous transplant benefits from a lower non-relapse mortality, the absence of graft-versus-host disease (GVHD), and a better quality of life for long-term survivors. The recent use of intravenous busulfan (IVBU) with high-dose melphalan, better monitoring of minimal residual disease (MRD), and maintenance therapy post autografting bring new interest. Few retrospective studies compared the outcome following alternative donor versus autologous transplants for remission consolidation. Genoidentical and phenoidentical allogeneic stem cell transplantations are undisputed gold standards, but there are no data showing the superiority of alternative allogeneic donor over autologous transplantation, at the time of undetectable MRD, in patients with good- and intermediate-1 risk acute myelocytic leukemia (AML) in first complete remission (CR1), acute promyelocytic leukemia in second complete remission (CR2), and Philadelphia chromosome-positive (Ph(+)) acute lymphocytic leukemia (ALL).

  16. Hematopoietic stem cell transplantation for infantile osteopetrosis

    NARCIS (Netherlands)

    Orchard, Paul J.; Fasth, Anders L.; Le Rademacher, Jennifer L.; He, Wensheng; Boelens, Jaap Jan; Horwitz, Edwin M.; Al-Seraihy, Amal; Ayas, Mouhab; Bonfim, Carmem M.; Boulad, Farid; Lund, Troy; Buchbinder, David K.; Kapoor, Neena; OBrien, Tracey A.; Perez, Miguel A Diaz; Veys, Paul A.; Eapen, Mary

    2015-01-01

    We report the international experience in outcomes after related and unrelated hematopoietic transplantation for infantile osteopetrosis in 193 patients. Thirty-four percent of transplants used grafts from HLA-matched siblings, 13% from HLA-mismatched relatives, 12% from HLA-matched, and 41% from HL

  17. Allogeneic haematopoietic stem cell transplantation for mitochondrial neurogastrointestinal encephalomyopathy

    NARCIS (Netherlands)

    Halter, Joerg P.; Schuepbach, W. Michael M.; Mandel, Hanna; Casali, Carlo; Orchard, Kim; Collin, Matthew; Valcarcel, David; Rovelli, Attilio; Filosto, Massimiliano; Dotti, Maria T.; Marotta, Giuseppe; Pintos, Guillem; Barba, Pere; Accarino, Anna; Ferra, Christelle; Illa, Isabel; Beguin, Yves; Bakker, Jaap A.; Boelens, Jaap J.; de Coo, Irenaeus F. M.; Fay, Keith; Sue, Carolyn M.; Nachbaur, David; Zoller, Heinz; Sobreira, Claudia; Simoes, Belinda Pinto; Hammans, Simon R.; Savage, David; Marti, Ramon; Chinnery, Patrick F.; Elhasid, Ronit; Gratwohl, Alois; Hirano, Michio

    2015-01-01

    Haematopoietic stem cell transplantation has been proposed as treatment for mitochondrial neurogastrointestinal encephalomyopathy, a rare fatal autosomal recessive disease due to TYMP mutations that result in thymidine phosphorylase deficiency. We conducted a retrospective analysis of all known pati

  18. Strategies in Haploidentical Stem Cell Transplantation in Adults

    Directory of Open Access Journals (Sweden)

    Ulaş D. Bayraktar

    2013-12-01

    Full Text Available Haploidentical related donors are alternative stem cell sources for patients without human leukocyte antigen (HLA-matched related or unrelated donors. Immediate access to the donor, availability for patients with rare haplotypes, ease of stem cell procurement, and lack of a requirement for a physical cord blood bank or an extensive HLA database render this type of hematopoietic stem cell transplantation particularly attractive despite the high histoincompatibility barrier between the recipient and the haploidentical graft. In this review, we answer the following questions: 1 What are the current transplant strategies used to overcome the histoincompatibility barrier in haploidentical stem cell transplantation and their clinical results? 2 How should we choose the donor when there is more than one available haploidentical donor? 3 How does transplantation from haploidentical donors compare to that from umbilical cord blood?

  19. Hematopoietic stem cell transplantation for infantile osteopetrosis.

    Science.gov (United States)

    Orchard, Paul J; Fasth, Anders L; Le Rademacher, Jennifer; He, Wensheng; Boelens, Jaap Jan; Horwitz, Edwin M; Al-Seraihy, Amal; Ayas, Mouhab; Bonfim, Carmem M; Boulad, Farid; Lund, Troy; Buchbinder, David K; Kapoor, Neena; O'Brien, Tracey A; Perez, Miguel A Diaz; Veys, Paul A; Eapen, Mary

    2015-07-01

    We report the international experience in outcomes after related and unrelated hematopoietic transplantation for infantile osteopetrosis in 193 patients. Thirty-four percent of transplants used grafts from HLA-matched siblings, 13% from HLA-mismatched relatives, 12% from HLA-matched, and 41% from HLA-mismatched unrelated donors. The median age at transplantation was 12 months. Busulfan and cyclophosphamide was the most common conditioning regimen. Long-term survival was higher after HLA-matched sibling compared to alternative donor transplantation. There were no differences in survival after HLA-mismatched related, HLA-matched unrelated, or mismatched unrelated donor transplantation. The 5- and 10-year probabilities of survival were 62% and 62% after HLA-matched sibling and 42% and 39% after alternative donor transplantation (P = .01 and P = .002, respectively). Graft failure was the most common cause of death, accounting for 50% of deaths after HLA-matched sibling and 43% of deaths after alternative donor transplantation. The day-28 incidence of neutrophil recovery was 66% after HLA-matched sibling and 61% after alternative donor transplantation (P = .49). The median age of surviving patients is 7 years. Of evaluable surviving patients, 70% are visually impaired; 10% have impaired hearing and gross motor delay. Nevertheless, 65% reported performance scores of 90 or 100, and in 17%, a score of 80 at last contact. Most survivors >5 years are attending mainstream or specialized schools. Rates of veno-occlusive disease and interstitial pneumonitis were high at 20%. Though allogeneic transplantation results in long-term survival with acceptable social function, strategies to lower graft failure and hepatic and pulmonary toxicity are urgently needed.

  20. Total body irradiation in hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Fundagul Andic

    2014-06-01

    Full Text Available Total body irradiation is used in conjunction with chemotherapy as a conditioning regimen in the treatment of many disease such as leukemia, myelodysplastic syndrome, aplastic anemia, multiple myeloma and lymphoma prior to the hematopoetic stem cell transplantation. The main purposes of the hematopoetic stem cell transplantation are eradication of the recipient bone marrow and any residual cancer cells, creation of space in the receipient bone marrow for donor hematopoetic stem cells, and immunosuppression to prevent rejection of donor stem cells in the case of an allotransplant. [Archives Medical Review Journal 2014; 23(3.000: 398-410

  1. Hematopoietic stem cell transplantation in Europe 2014: more than 40 000 transplants annually.

    Science.gov (United States)

    Passweg, J R; Baldomero, H; Bader, P; Bonini, C; Cesaro, S; Dreger, P; Duarte, R F; Dufour, C; Kuball, J; Farge-Bancel, D; Gennery, A; Kröger, N; Lanza, F; Nagler, A; Sureda, A; Mohty, M

    2016-06-01

    A record number of 40 829 hematopoietic stem cell transplantation (HSCT) in 36 469 patients (15 765 allogeneic (43%), 20 704 autologous (57%)) were reported by 656 centers in 47 countries to the 2014 survey. Trends include: continued growth in transplant activity, more so in Eastern European countries than in the west; a continued increase in the use of haploidentical family donors (by 25%) and slower growth for unrelated donor HSCT. The use of cord blood as a stem cell source has decreased again in 2014. Main indications for HSCT were leukemias: 11 853 (33%; 96% allogeneic); lymphoid neoplasias; 20 802 (57%; 11% allogeneic); solid tumors; 1458 (4%; 3% allogeneic) and non-malignant disorders; 2203 (6%; 88% allogeneic). Changes in transplant activity include more allogeneic HSCT for AML in CR1, myeloproliferative neoplasm (MPN) and aplastic anemia and decreasing use in CLL; and more autologous HSCT for plasma cell disorders and in particular for amyloidosis. In addition, data on numbers of teams doing alternative donor transplants, allogeneic after autologous HSCT, autologous cord blood transplants are presented.

  2. [Nosocomial infection in patients receiving a solid organ transplant or haematopoietic stem cell transplant].

    Science.gov (United States)

    Moreno Camacho, Asunción; Ruiz Camps, Isabel

    2014-01-01

    Bacterial infections are the most common infections in solid organ transplant recipients. These infections occur mainly in the first month after transplantation and are hospital-acquired. Nosocomial infections cause significant morbidity and are the most common cause of mortality in this early period of transplantation. These infections are caused by multi-drug resistant (MDR) microorganisms, mainly Gram-negative enterobacteria, non-fermentative Gram-negative bacilli, enterococci, and staphylococci. The patients at risk of developing nosocomial bacterial infections are those previously colonized with MDR bacteria while on the transplant waiting list. Intravascular catheters, the urinary tract, the lungs, and surgical wounds are the most frequent sources of infection. Preventive measures are the same as those applied in non-immunocompromised, hospitalized patients except in patients at high risk for developing fungal infection. These patients need antifungal therapy during their hospitalization, and for preventing some bacterial infections in the early transplant period, patients need vaccinations on the waiting list according to the current recommendations. Although morbidity and mortality related to infectious diseases have decreased during the last few years in haematopoietic stem cell transplant recipients, they are still one of the most important complications in this population. Furthermore, as occurs in the general population, the incidence of nosocomial infections has increased during the different phases of transplantation. It is difficult to establish general preventive measures in these patients, as there are many risk factors conditioning these infections. Firstly, they undergo multiple antibiotic treatments and interventions; secondly, there is a wide variability in the degree of neutropenia and immunosuppression among patients, and finally they combine hospital and home stay during the transplant process. However, some simple measures could be

  3. Autologous hematopoietic stem cell transplantation in classical Hodgkin's lymphoma

    Science.gov (United States)

    Cortez, Afonso José Pereira; Dulley, Frederico Luiz; Saboya, Rosaura; Mendrone Júnior, Alfredo; Amigo Filho, Ulisses; Coracin, Fabio Luiz; Buccheri, Valéria; Linardi, Camila da Cruz Gouveia; Ruiz, Milton Artur; Chamone, Dalton de Alencar Fischer

    2011-01-01

    Background Hodgkin's lymphoma has high rates of cure, but in 15% to 20% of general patients and between 35% and 40% of those in advanced stages, the disease will progress or will relapse after initial treatment. For this group, hematopoietic stem cell transplantation is considered one option of salvage therapy. Objectives To evaluate a group of 106 patients with Hodgkin's lymphoma, who suffered relapse or who were refractory to treatment, submitted to autologous hematopoietic stem cell transplantation in a single transplant center. Methods A retrospective study was performed with data collected from patient charts. The analysis involved 106 classical Hodgkin's lymphoma patients who were consecutively submitted to high-dose chemotherapy followed by autologous transplants in a single institution from April 1993 to December 2006. Results The overall survival rates of this population at five and ten years were 86% and 70%, respectively. The disease-free survival was approximately 60% at five years. Four patients died of procedure-related causes but relapse of classical Hodgkin's lymphoma after transplant was the most frequent cause of death. Univariate analysis shows that sensitivity to pre-transplant treatment and hemoglobin < 10 g/dL at diagnosis had an impact on patient survival. Unlike other studies, B-type symptoms did not seem to affect overall survival. Lactic dehydrogenase and serum albumin concentrations analyzed at diagnosis did not influence patient survival either. Conclusion Autologous hematopoietic stem cell transplantation is an effective treatment strategy for early and late relapse in classical Hodgkin's lymphoma for cases that were responsive to pre-transplant chemotherapy. Refractory to treatment is a sign of worse prognosis. Additionally, a hemoglobin concentration below 10 g/dL at diagnosis of Hodgkin's lymphoma has a negative impact on the survival of patients after transplant. As far as we know this relationship has not been previously reported

  4. Autologous hematopoietic stem cell transplantation in classical Hodgkin's lymphoma

    Directory of Open Access Journals (Sweden)

    Afonso José Pereira Cortez

    2011-02-01

    Full Text Available BACKGROUND: Hodgkin's lymphoma has high rates of cure, but in 15% to 20% of general patients and between 35% and 40% of those in advanced stages, the disease will progress or will relapse after initial treatment. For this group, hematopoietic stem cell transplantation is considered one option of salvage therapy. OBJECTIVES: To evaluate a group of 106 patients with Hodgkin's lymphoma, who suffered relapse or who were refractory to treatment, submitted to autologous hematopoietic stem cell transplantation in a single transplant center. METHODS: A retrospective study was performed with data collected from patient charts. The analysis involved 106 classical Hodgkin's lymphoma patients who were consecutively submitted to high-dose chemotherapy followed by autologous transplants in a single institution from April 1993 to December 2006. RESULTS: The overall survival rates of this population at five and ten years were 86% and 70%, respectively. The disease-free survival was approximately 60% at five years. Four patients died of procedure-related causes but relapse of classical Hodgkin's lymphoma after transplant was the most frequent cause of death. Univariate analysis shows that sensitivity to pre-transplant treatment and hemoglobin < 10 g/dL at diagnosis had an impact on patient survival. Unlike other studies, B-type symptoms did not seem to affect overall survival. Lactic dehydrogenase and serum albumin concentrations analyzed at diagnosis did not influence patient survival either. CONCLUSION: Autologous hematopoietic stem cell transplantation is an effective treatment strategy for early and late relapse in classical Hodgkin's lymphoma for cases that were responsive to pre-transplant chemotherapy. Refractory to treatment is a sign of worse prognosis. Additionally, a hemoglobin concentration below 10 g/dL at diagnosis of Hodgkin's lymphoma has a negative impact on the survival of patients after transplant. As far as we know this relationship has not

  5. Autologous mesenchymal stem cells transplantation in adriamycin-induced cardiomyopathy

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jing; LI Geng-shan; LI Guo-cao; ZHOU Qing; LI Wen-qiang; XU Hong-xin

    2005-01-01

    @@ Recent studies have suggested benefits of mesenchymal stem cells (MSCs) transplantation for the regeneration of cardiac tissue and function improvement of regionally infracted myocardium, but its effects on global heart failure is still little known. This study suggested the capacity of MSCs to transdifferentiate to cardiac cells in a nonischemic cardiomyopathic setting, and the effect of the cells on heart function.

  6. Sexual Health in Hematopoietic Stem Cell Transplant Recipients

    OpenAIRE

    2015-01-01

    Hematopoietic stem cell transplantation (HSCT) plays a central role in patients with malignant and, increasingly, nonmalignant conditions. As the number of transplants increases and the survival rate improves, long-term complications are important to recognize and treat to maintain quality of life. Sexual dysfunction is a commonly described but relatively often underestimated complication after HSCT. Conditioning regimens, generalized or genital graft-versus-host disease, medications, and car...

  7. 78 FR 47714 - Advisory Council on Blood Stem Cell Transplantation; Notice of Meeting

    Science.gov (United States)

    2013-08-06

    ... HUMAN SERVICES Health Resources and Services Administration Advisory Council on Blood Stem Cell... Health Service Act, as amended), the Advisory Council on Blood Stem Cell Transplantation (ACBSCT) advises... Advancing Hematopoietic Stem Cell Transplantation for Hemoglobinopathies. The Council also will...

  8. 78 FR 23571 - Advisory Council on Blood Stem Cell Transplantation; Notice of Meeting

    Science.gov (United States)

    2013-04-19

    ... HUMAN SERVICES Health Resources and Services Administration Advisory Council on Blood Stem Cell... amended), the Advisory Council on Blood Stem Cell Transplantation (ACBSCT) advises the Secretary of the... Hematopoietic Stem Cell Transplantation for Hemoglobinopathies. The Council will also hear presentations...

  9. Oral changes in individuals undergoing hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Regina Haddad Barrach

    2015-04-01

    Full Text Available INTRODUCTION: Patients undergoing hematopoietic stem cell transplantation receive high doses of chemotherapy and radiotherapy, which cause severe immunosuppression.OBJECTIVE: To report an oral disease management protocol before and after hematopoietic stem cell transplantation.METHODS: A prospective study was carried out with 65 patients aged > 18 years, with hematological diseases, who were allocated into two groups: A (allogeneic transplant, 34 patients; B (autologous transplant, 31 patients. A total of three dental status assessments were performed: in the pre-transplantation period (moment 1, one week after stem cell infusion (moment 2, and 100 days after transplantation (moment 3. In each moment, oral changes were assigned scores and classified as mild, moderate, and severe risks.RESULTS: The most frequent pathological conditions were gingivitis, pericoronitis in the third molar region, and ulcers at the third moment assessments. However, at moments 2 and 3, the most common disease was mucositis associated with toxicity from the drugs used in the immunosuppression.CONCLUSION: Mucositis accounted for the increased score and potential risk of clinical complications. Gingivitis, ulcers, and pericoronitis were other changes identified as potential risk factors for clinical complications.

  10. Allogenic bone narrow transplantation in sickle-cell diseases.

    Directory of Open Access Journals (Sweden)

    Belinda Pinto Simões

    Full Text Available SUMMARY Sickle-cell diseases are the most common inherited hemoglobinopathies worldwide. Improvement in survival has been seen in the last decades with the introduction of careful screening and prevention of complications and the introduction of hydroxyurea. Stem-cell transplantation is currently the only curative option for these patients and has been indicated for patients with neurological events, repeated vaso-occlusive crisis, any organ damage or presence of red blood cell antibodies. Related bone-marrow or cord-blood transplant has shown an overall survival of more than 90% with a disease-free survival of 90% in 1,000 patients transplanted in the last decades. The use of unrelated donors unfortunately has not shown the same good results, but better typing methods and improved support may improve the outcome with this source of stem cells in the future. In Brazil, only recently stem cell transplant from related donors has been included in the procedures performed in the public health system. The use of related bone marrow or cord blood and a myeloablative conditioning regimen are considered standard of care for patients with sickle-cell diseases. Transplants with non-myeloablative regimens, unrelated donors or haploidentical donors should be performed only in controlled clinical trials.

  11. IN UTERO HAEMATOPOIETIC STEM CELL TRANSPLANTATION (IUHSCT

    Directory of Open Access Journals (Sweden)

    Aurelio Maggio

    2009-06-01

    Full Text Available

    In utero haematopoietic stem cell transplantation (IUHSCT is a non-myeloablative approach for the prenatal treatment of genetic disorders. However, in target disorders, where there is not a selective advantage for donor cells, a useful donor-cell  chimerism  has not been achieved 

    There are three  possible  barriers  to engraftment following IUHSCT :  limited space in the fetus due to host-cell competition; the large number of donor cells needed, and the immunological asset of recipient .

    Animal models have shown different levels of resistance to IUHSCT engraftment.  In primate, goat, rat and mouse  the levels of engraftment that has been achieved were low and not  therapeutic.

  12. Predictors for severe cardiac complications after hematopoietic stem cell transplantation.

    Science.gov (United States)

    Sakata-Yanagimoto, M; Kanda, Y; Nakagawa, M; Asano-Mori, Y; Kandabashi, K; Izutsu, K; Imai, Y; Hangaishi, A; Kurokawa, M; Tsujino, S; Ogawa, S; Chiba, S; Motokura, T; Hirai, H

    2004-05-01

    The value of pre-transplant factors for predicting the development of cardiac complications after transplantation has been inconsistent among studies. We analyzed the impact of pre-transplant factors on the incidence of severe cardiac complications in 164 hematopoietic stem cell transplant recipients. We identified eight patients (4.8%) who experienced grade III or IV cardiac complications according to the Bearman criteria. Seven died of cardiac causes a median of 3 days after the onset of cardiac complications. On univariate analysis, both the cumulative dose of anthracyclines and the use of anthracyclines within 60 days before transplantation affected the incidence of severe cardiac complications (P=0.0091 and 0.011). The dissociation of heart rate and body temperature, which reflects "relative tachycardia", was also associated with a higher incidence of cardiac complications (P=0.024). None of the variables obtained by electrocardiography or echocardiography were useful for predicting cardiac complications after transplantation, although the statistical power might not be sufficient to detect the usefulness of ejection fraction. On a multivariate analysis, the cumulative dose of anthracyclines was the only independent significant risk factor for severe cardiac complications. We conclude that the cumulative dose of anthracyclines is the most potent predictor of cardiac complications and the administration of anthracyclines should be avoided within two months before transplantation.

  13. Stem cell microencapsulation for phenotypic control, bioprocessing, and transplantation.

    Science.gov (United States)

    Wilson, Jenna L; McDevitt, Todd C

    2013-03-01

    Cell microencapsulation has been utilized for decades as a means to shield cells from the external environment while simultaneously permitting transport of oxygen, nutrients, and secretory molecules. In designing cell therapies, donor primary cells are often difficult to obtain and expand to appropriate numbers, rendering stem cells an attractive alternative due to their capacities for self-renewal, differentiation, and trophic factor secretion. Microencapsulation of stem cells offers several benefits, namely the creation of a defined microenvironment which can be designed to modulate stem cell phenotype, protection from hydrodynamic forces and prevention of agglomeration during expansion in suspension bioreactors, and a means to transplant cells behind a semi-permeable barrier, allowing for molecular secretion while avoiding immune reaction. This review will provide an overview of relevant microencapsulation processes and characterization in the context of maintaining stem cell potency, directing differentiation, investigating scalable production methods, and transplanting stem cells for clinically relevant disorders.

  14. Endovascular transplantation of stem cells to the injured rat CNS

    Energy Technology Data Exchange (ETDEWEB)

    Lundberg, Johan; Soederman, Mikael; Andersson, Tommy; Holmin, Staffan [Karolinska University Hospital, Department of Clinical Neuroscience, Karolinska Institutet, Department of Neuroradiology, Stockholm (Sweden); Le Blanc, Katarina [Karolinska University Hospital, Department of Stem Cell Research, Karolinska Institutet, Department of Clinical Immunology, Stockholm (Sweden)

    2009-10-15

    Transplantation procedures using intraparenchymal injection of stem cells result in tissue injury in addition to associated surgical risks. Intravenous injection of mesenchymal stem cells gives engraftment to lesions, but the method has low efficiency and specificity. In traumatic brain injuries (TBI), there is a transient breakdown of the blood-brain barrier and an inflammatory response, which increase migration of cells from blood to parenchyma. The aim of this investigation was to analyze the effect of intra-arterial administration on cellular engraftment. Experimental TBI was produced in a rat model. Endovascular technique was used to administer human mesenchymal stem cells in the ipsilateral internal carotid artery. Evaluation of engraftment and side effects were performed by immunohistochemical analysis of the brain and several other organs. The results were compared to intravenous administration of stem cells. Intra-arterial transplantion of mesenchymal stem cells resulted in central nervous system (CNS) engraftment without thromboembolic ischemia. We observed a significantly higher number of transplanted cells in the injured hemisphere after intra-arterial compared to intravenous administration both 1 day (p<0.01) and 5 days (p<0.05) after the transplantation. Some cells were also detected in the spleen but not in the other organs analyzed. Selective intra-arterial administration of mesenchymal stem cells to the injured CNS is a minimally invasive method for transplantation. The method is significantly more efficient than the intravenous route and causes no side effects in the current model. The technique can potentially be used for repeated transplantation to the CNS after TBI and in other diseases. (orig.)

  15. 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...

  16. Brain microvascular endothelial cell transplantation ameliorates ischemic white matter damage.

    Science.gov (United States)

    Puentes, Sandra; Kurachi, Masashi; Shibasaki, Koji; Naruse, Masae; Yoshimoto, Yuhei; Mikuni, Masahiko; Imai, Hideaki; Ishizaki, Yasuki

    2012-08-21

    Ischemic insults affecting the internal capsule result in sensory-motor disabilities which adversely affect the patient's life. Cerebral endothelial cells have been reported to exert a protective effect against brain damage, so the transplantation of healthy endothelial cells might have a beneficial effect on the outcome of ischemic brain damage. In this study, endothelin-1 (ET-1) was injected into the rat internal capsule to induce lacunar infarction. Seven days after ET-1 injection, microvascular endothelial cells (MVECs) were transplanted into the internal capsule. Meningeal cells or 0.2% bovine serum albumin-Hank's balanced salt solution were injected as controls. Two weeks later, the footprint test and histochemical analysis were performed. We found that MVEC transplantation improved the behavioral outcome based on recovery of hind-limb rotation angle (P<0.01) and induced remyelination (P<0.01) compared with the control groups. Also the inflammatory response was repressed by MVEC transplantation, judging from fewer ED-1-positive activated microglial cells in the MVEC-transplanted group than in the other groups. Elucidation of the mechanisms by which MVECs ameliorate ischemic damage of the white matter may provide important information for the development of effective therapies for white matter ischemia.

  17. Allogeneic stem cell transplant for adults with myelodysplastic syndromes: relevance of pre-transplant disease status.

    Science.gov (United States)

    Busca, Alessandro; Pecoraro, Clara; Giaccone, Luisa; Bruno, Benedetto; Allione, Bernardino; Corsetti, Maria Teresa; Pini, Massimo; Marmont, Filippo; Audisio, Ernesta; D'Ardia, Stefano; Frairia, Chiara; Castiglione, Anna; Ciccone, Giovannino; Levis, Alessandro; Vitolo, Umberto; Falda, Michele

    2014-04-01

    The aim of the present study was to investigate the outcome of 94 adult patients with myelodysplasia (MDS) who received an allogeneic stem cell transplant between January 1995 and September 2010 in two Italian hematology centers. At the time of transplant, 53 patients (56%) had relapsed/refractory disease. The cumulative incidence of grades II-IV acute graft-versus-host disease (GVHD) and chronic GVHD was 33% (95% confidence interval [CI] 21-45%) and 78% (95% CI 66-90%), respectively. The cumulative incidence of transplant-related mortality (TRM) at 100 days was 13% (95% CI 6-21%). The 2-year progression free survival (PFS) and overall survival (OS) were 41% (95% CI 31-51%) and 49% (95% CI 38-59%), respectively. On multivariate analysis, advanced disease stage at transplant was the major independent variable associated with an inferior 2-year PFS (HR 3.66, 95% CI 1.98-6.76) and OS (HR 3.68, 95% CI 1.95-6.93). Use of an alternative donor was an independent variable associated with TRM (HR 3.18, 95% CI 1.31-7.72). In conclusion, our data suggest that disease status at the time of transplant is the major predictor for improved PFS and OS, and treatments required to reach this goal may have value in leading to an improved outcome.

  18. Transplantation tolerance mediated by regulatory T cells in mice

    Institute of Scientific and Technical Information of China (English)

    冯宁翰; 吴宏飞; 吴军; 张炜; 眭元庚; 贺厚光; 张春雷; 郑峻松

    2004-01-01

    Background With potent suppressive effect on responder T cells, CD4+CD25+ regulatory T (Treg) cells have become the focus of attention only recently and they may play an important role in transplantation tolerance. However, the mechanism of action is not clear. This study was designed to assess the possibility of using CD4+CD25+ Treg cells to induce transplantation tolerance and to investigate their mechanism of action.Methods CD4+CD25+ Treg cells were isolated using magnetic cell separation techniques. Mixed lymphocyte reactions were used to assess the ability of Treg cells to suppress effector T cells. Before skin transplantation, various numbers of CD4+CD25+Treg cells, which have been induced using complex skin antigens from the donor, were injected into the host mice either intraperitoneally (0.5×105, 1×105, 2×105, 3×105, 4×105, or 5×105) or by injection through the tail vein (5×103, 1×104, 2×104, 5×104, 1×105, 2×105). Skin grafts from two different donor types were used to assess whether the induced Treg cells were antigen-specific. The survival time of the allografts were observed. Single photon emission computed tomography was also used to determine the distribution of Treg cells before and after transplantation.Results Treg cells have suppressive effect on mixed lymphocyte reactions. Grafts survived longer in mice receiving CD4+CD25+ Treg cell injections than in control mice. There was a significant difference between groups receiving intraperitoneal injection of either 2×105 or 3×105 CD4+CD25+Treg cells and the control group (P<0.05, respectively). Better results were achieved when Treg cells were injected via the tail vein than when injected intraperitoneally. The transplantation tolerance induced by CD4+CD25+ Treg cells was donor-specific. Analysis of the localization of Treg cells revealed that Treg cells mainly migrated from the liver to the allografts and the spleen.Conclusions CD4+CD25+Treg cells can induce donor

  19. Advances in Cell Transplantation Therapy for Diseased Myocardium

    Directory of Open Access Journals (Sweden)

    Outi M. Villet

    2011-01-01

    Full Text Available The overall objective of cell transplantation is to repopulate postinfarction scar with contractile cells, thus improving systolic function, and to prevent or to regress the remodeling process. Direct implantation of isolated myoblasts, cardiomyocytes, and bone-marrow-derived cells has shown prospect for improved cardiac performance in several animal models and patients suffering from heart failure. However, direct implantation of cultured cells can lead to major cell loss by leakage and cell death, inappropriate integration and proliferation, and cardiac arrhythmia. To resolve these problems an approach using 3-dimensional tissue-engineered cell constructs has been investigated. Cell engineering technology has enabled scaffold-free sheet development including generation of communication between cell graft and host tissue, creation of organized microvascular network, and relatively long-term survival after in vivo transplantation.

  20. Advances in haploidentical stem cell transplantation for hematologic malignancies.

    Science.gov (United States)

    Montoro, Juan; Sanz, Jaime; Sanz, Guillermo F; Sanz, Miguel A

    2016-08-01

    One of the most important advances in allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the use of alternative donors and cell sources, such as haploidentical transplants (haplo-HSCT) from family donors. Several approaches have been developed to overcome the challenging bidirectional alloreactivity. We discuss these approaches, including ex vivo T-cell-depleted grafts with megadose of CD34(+) cells, not requiring immunosuppression after allogeneic transplantation for graft-versus-host disease (GVHD) prophylaxis, and other strategies using unmanipulated T-cell-replete grafts with intensive immunosuppression or post-transplantation cyclophosphamide to minimize the GVHD. We also address the role of other strategies developed in the context of the haplo-HSCT platforms, such as ex vivo selective depletion of alloreactive donor T-cell subpopulations, infusion of antigen-specific T-cells against several pathogens, and infusion of regulatory T-cells, among other experimental approaches. Finally, some considerations about the selection of the most suitable donor, when more than one family member is available, are also addressed.

  1. Clinical trials for stem cell transplantation: when are they needed?

    Science.gov (United States)

    Van Pham, Phuc

    2016-04-27

    In recent years, both stem cell research and the clinical application of these promising cells have increased rapidly. About 1000 clinical trials using stem cells have to date been performed globally. More importantly, more than 10 stem cell-based products have been approved in some countries. With the rapid growth of stem cell applications, some countries have used clinical trials as a tool to diminish the rate of clinical stem cell applications. However, the point at which stem cell clinical trials are essential remains unclear. This commentary discusses when stem cell clinical trials are essential for stem cell transplantation therapies.

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    ). 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......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...... 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...

  3. 77 FR 22791 - Advisory Council on Blood Stem Cell Transplantation; Notice of Meeting

    Science.gov (United States)

    2012-04-17

    ... HUMAN SERVICES Health Resources and Services Administration Advisory Council on Blood Stem Cell... Health Service Act, as amended), the Advisory Council on Blood Stem Cell Transplantation (ACBSCT) advises... Thawing and Washing, (4) Access to Transplantation, and (5) Advancing Hematopoietic Stem...

  4. Symptoms after hospital discharge following hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Gamze Oguz

    2014-01-01

    Full Text Available Aims: The purposes of this study were to assess the symptoms of hematopoietic stem cell transplant patients after hospital discharge, and to determine the needs of transplant patients for symptom management. Materials and Methods: The study adopted a descriptive design. The study sample comprised of 66 hematopoietic stem cell transplant patients. The study was conducted in Istanbul. Data were collected using Patient Information Form and Memorial Symptom Assessment Scale (MSAS. Results: The frequency of psychological symptoms in hematopoietic stem cell transplant patients after discharge period (PSYCH subscale score 2.11 (standard deviation (SD = 0.69, range: 0.93-3.80 was higher in hematopoietic stem cell transplant patients than frequency of physical symptoms (PHYS subscale score: 1.59 (SD = 0.49, range: 1.00-3.38. Symptom distress caused by psychological and physical symptoms were at moderate level (Mean = 1.91, SD = 0.60, range: 0.95-3.63 and most distressing symptoms were problems with sexual interest or activity, difficulty sleeping, and diarrhea. Patients who did not have an additional chronic disease obtained higher MSAS scores. University graduates obtained higher Global Distress Index (GDI subscale and total MSAS scores with comparison to primary school graduates. Total MSAS, MSAS-PHYS subscale, and MSAS-PSYCH subscale scores were higher in patients with low level of income (P < 0.05. The patients (98.5% reported to receive education about symptom management after hospital discharge. Conclusions: Hematopoietic stem cell transplant patients continue to experience many distressing physical or psychological symptoms after discharge and need to be supported and educated for the symptom management.

  5. Preimplantation HLA typing for stem cell transplantation treatment of hemoglobinopathies

    Directory of Open Access Journals (Sweden)

    Anver Kuliev

    2014-09-01

    Full Text Available Preimplantation genetic diagnosis (PGD for HLA typing is steadily becoming an option for at risk couples with thalassemic children, requiring HLA matched bone marrow transplantation treatment. The paper presents the world’s largest PGD experience of 475 cases for over 2 dozens thalassemia mutations, resulting in birth of 132 unaffected children. A total of 146 cases were performed together with preimplantation HLA typing, resulting in detection and transfer of HLA matched unaffected embryos in 83 of them, yielding the birth of 16 HLA matched children, potential donors for their affected siblings. The presented experience of HLA matched stem cell transplantation for thalassemia, following PGD demonstrated a successful hematopoietic reconstitution both for younger and older patients. The data show that PGD is an efficient approach for HLA matched stem cell transplantation treatment for thalassemia.

  6. Allogeneic Mesenchymal Stem Cell Transplantation in Dogs With Keratoconjunctivitis Sicca

    Science.gov (United States)

    Bittencourt, Maura K. W.; Barros, Michele A.; Martins, João Flávio P.; Vasconcellos, Jose Paulo C.; Morais, Bruna P.; Pompeia, Celine; Bittencourt, Matheus Domingues; Evangelho, Karine dos Santos; Kerkis, Irina; Wenceslau, Cristiane V.

    2016-01-01

    Keratoconjunctivitis sicca (KCS) is a dysfunction in tear production associated with clinical signs, which include conjunctival hyperemia, ocular discharge, discomfort, pain, and, eventually, corneal vascularization and pigmentation. Immunosuppressive drugs are routinely administrated for long periods to treat KCS but with side effects and limited results. Evaluation of the clinical benefits of intralacrimal transplantation of allogeneic mesenchymal stem cells (MSCs) in dogs with mild–moderate and severe KCS was done. A total of 24 eyes with KCS from 15 dogs of different breeds were enrolled in the present study. A single transplantation of MSCs (1 × 106) directly into lacrimal glands (dorsal and third eyelid) was performed. The Schirmer tear tests (STTs) and ocular surface improvements were used to assess short- and long-term effects of these cells. The STTs were carried out on day 0 (before MSCs transplantation) and on days 7, 14, 21, and 28, as well as 6 and 12 months after MSC transplantation. Our data demonstrate that allogeneic MSC transplantation in KCS dogs is safe since no adverse effects were observed immediately after transplantation and in short- and long-term follow-ups. A statistically significant increase in the STT and ocular surface improvements was found in all eyes studied. In all the eyes with mild–moderate KCS, STT values reverted to those of healthy eyes, while in eyes with severe KCS, although complete reversion was not found, there was improvement in tear production and in other clinical signs. Our study shows that a single dose of a low number of MSCs can be used to treat KCS in dogs. In contrast to immunosuppressive drug use, MSC transplantation has an effect over a long period (up to 12 months), even after a single administration, and does not require daily drug administration. PMID:28003932

  7. Mesenchymal stromal cells and hematopoietic stem cell transplantation.

    Science.gov (United States)

    Bernardo, Maria Ester; Fibbe, Willem E

    2015-12-01

    Mesenchymal stromal cells (MSCs) comprise a heterogeneous population of multipotent cells that can be isolated from various human tissues and culture-expanded ex vivo for clinical use. Due to their immunoregulatory properties and their ability to secrete growth factors, MSCs play a key role in the regulation of hematopoiesis and in the modulation of immune responses against allo- and autoantigens. In light of these properties, MSCs have been employed in clinical trials in the context of hematopoietic stem cell transplantation (HSCT) to facilitate engraftment of hematopoietic stem cells (HSCs) and to prevent graft failure, as well as to treat steroid-resistant acute graft-versus-host disease (GvHD). The available clinical evidence derived from these studies indicates that MSC administration is safe. Moreover, promising preliminary results in terms of efficacy have been reported in some clinical trials, especially in the treatment of acute GvHD. In this review we critically discuss recent advances in MSC therapy by reporting on the most relevant studies in the field of HSCT.

  8. Multiscale patterned transplantable stem cell patches for bone tissue regeneration.

    Science.gov (United States)

    Kim, Jangho; Bae, Won-Gyu; Choung, Han-Wool; Lim, Ki Taek; Seonwoo, Hoon; Jeong, Hoon Eui; Suh, Khap-Yang; Jeon, Noo Li; Choung, Pill-Hoon; Chung, Jong Hoon

    2014-11-01

    Stem cell-based therapy has been proposed as an enabling alternative not only for the treatment of diseases but also for the regeneration of tissues beyond complex surgical treatments or tissue transplantation. In this study, we approached a conceptual platform that can integrate stem cells into a multiscale patterned substrate for bone regeneration. Inspired by human bone tissue, we developed hierarchically micro- and nanopatterned transplantable patches as synthetic extracellular matrices by employing capillary force lithography in combination with a surface micro-wrinkling method using a poly(lactic-co-glycolic acid) (PLGA) polymer. The multiscale patterned PLGA patches were highly flexible and showed higher tissue adhesion to the underlying tissue than did the single nanopatterned patches. In response to the anisotropically multiscale patterned topography, the adhesion and differentiation of human mesenchymal stem cells (hMSCs) were sensitively controlled. Furthermore, the stem cell patch composed of hMSCs and transplantable PLGA substrate promoted bone regeneration in vivo when both the micro- and nanotopography of the substrate surfaces were synergistically combined. Thus, our study concludes that multiscale patterned transplantable stem cell patches may have a great potential for bone regeneration as well as for various regenerative medicine approaches.

  9. Prolonged Survival of Transplanted Osteoblastic Cells Does Not Directly Accelerate the Healing of Calvarial Bone Defects.

    Science.gov (United States)

    Kitami, Megumi; Kaku, Masaru; Rocabado, Juan Marcelo Rosales; Ida, Takako; Akiba, Nami; Uoshima, Katsumi

    2016-09-01

    Considering the increased interest in cell-based bone regeneration, it is necessary to reveal the fate of transplanted cells and their substantive roles in bone regeneration. The aim of this study was to analyze the fate of transplanted cells and the effect of osteogenic cell transplantation on calvarial bone defect healing. An anti-apoptotic protein, heat shock protein (HSP) 27, was overexpressed in osteoblasts. Then, the treated osteoblasts were transplanted to calvarial bone defect and their fate was analyzed to evaluate the significance of transplanted cell survival. Transient overexpression of Hsp27 rescued MC3T3-E1 osteoblastic cells from H2 O2 -induced apoptosis without affecting osteoblastic differentiation in culture. Transplantation of Hsp27-overexpressing cells, encapsulated in collagen gel, showed higher proliferative activity, and fewer apoptotic cells in comparison with control cells. After 4-week of transplantation, both control cell- and Hsp27 overexpressed cell-transplanted groups showed significantly higher new bone formation in comparison with cell-free gel-transplantation group. Interestingly, the prolonged survival of transplanted osteoblastic cells by Hsp27 did not provide additional effect on bone healing. The transplanted cells in collagen gel survived for up to 4-week but did not differentiate into bone-forming osteoblasts. In conclusion, cell-containing collagen gel accelerated calvarial bone defect healing in comparison with cell-free collagen gel. However, prolonged survival of transplanted cells by Hsp27 overexpression did not provide additional effect. These results strongly indicate that cell transplantation-based bone regeneration cannot be explained only by the increment of osteogenic cells. Further studies are needed to elucidate the practical roles of transplanted cells that will potentiate successful bone regeneration. J. Cell. Physiol. 231: 1974-1982, 2016. © 2016 Wiley Periodicals, Inc.

  10. Pre-transplant weight loss predicts inferior outcome after allogeneic stem cell transplantation in patients with myelodysplastic syndrome.

    Science.gov (United States)

    Radujkovic, Aleksandar; Becker, Natalia; Benner, Axel; Penack, Olaf; Platzbecker, Uwe; Stölzel, Friedrich; Bornhäuser, Martin; Hegenbart, Ute; Ho, Anthony D; Dreger, Peter; Luft, Thomas

    2015-10-27

    Allogeneic stem cell transplantation (alloSCT) represents a curative therapeutic option for patients with myelodysplastic syndrome (MDS), but relapse and non-relapse mortality (NRM) limit treatment efficacy. Based on our previous observation in acute myeloid leukemia we investigated the impact of pre-transplant weight loss on post-transplant outcome in MDS patients. A total of 111 patients diagnosed with MDS according to WHO criteria transplanted between 2000 and 2012 in three different transplant centers were included into the analysis. Data on weight loss were collected from medical records prior to conditioning therapy and 3-6 months earlier. Patient, disease and transplant characteristics did not differ between patients with weight loss (2-5%, n = 17; > 5%, n = 17) and those without (n = 77). In a mixed effect model, weight loss was associated with higher risk MDS (p = 0.046). In multivariable analyses, pre-transplant weight loss exceeding 5% was associated with a higher incidence of relapse (p transplant weight loss of 2-5% and > 5% were independent predictors of worse disease-free (p = 0.023 and p transplantation. Prospective studies addressing pre-transplant nutritional interventions are highly warranted.

  11. Expansion of hematopoietic stem cells for transplantation: current perspectives

    Directory of Open Access Journals (Sweden)

    Schuster Jessica A

    2012-05-01

    Full Text Available Abstract Hematopoietic stem cells (HSCs are rare cells that have the unique ability to self-renew and differentiate into cells of all hematopoietic lineages. The expansion of HSCs has remained an important goal to develop advanced cell therapies for bone marrow transplantation and many blood disorders. Over the last several decades, there have been numerous attempts to expand HSCs in vitro using purified growth factors that are known to regulate HSCs. However, these attempts have been met with limited success for clinical applications. New developments in the HSC expansion field coupled with gene therapy and stem cell transplant should encourage progression in attractive treatment options for many disorders including hematologic conditions, immunodeficiencies, and genetic disorders.

  12. Oligodendrocyte-like cell transplantation for acute spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    Yongtao Xu; Anmin Chen; Feng Li; Hougeng Lu

    2011-01-01

    In this study, we used insulin-like growth factor-1 to induce bone marrow mesenchymal stem cells (MSCs) to differentiate into oligodendrocyte-like cells. Cell surface marker identification showed that they expressed myelin basic protein and galactosylceramide, two specific markers of oligodendrocytes. These cells were transplanted into rats with acute spinal cord injury at T10. At 8 weeks post-implantation, oligodendrocyte-like cells were observed to have survived at the injury site. The critical angle of the inclined plane, and Basso, Beattie and Bresnahan scores were all increased. Furthermore, latencies of motion-evoked and somatosensory-evoked potentials were decreased. These results demonstrate that transplantation of oligodendrocytic-induced MSCs promote functional recovery of injured spinal cord.

  13. Immunotherapeutic strategies against mucormycosis in haematopoietic stem cell transplantation.

    Science.gov (United States)

    Schmidt, Stanislaw; Tramsen, Lars; Schneider, Andreas; Balan, Ada; Lehrnbecher, Thomas

    2014-12-01

    Mucormycoses remain a serious complication in patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT). In these patients, mortality rates of mucormycosis reach up to 90%, which is due, at least in part, to the severe and prolonged immunosuppression after transplantation. Although prolonged neutropaenia is one of the most important risk factors for mucormycosis, other cell populations, such as CD4(+) T cells may also provide critical defence mechanisms against this infection. The management of mucormycosis includes antifungal therapy, surgery and, most importantly, the control of the underlying predisposing conditions, such as the correction of an impaired immune system. Here, we review the current data of granulocytes, antifungal T cells and natural killer cells regarding their activity against mucormycetes and regarding a potential immunotherapeutic approach. It is hoped that further animal studies and clinical trials assessing immunotherapeutic strategies will ultimately improve the poor prognosis of allogeneic HSCT recipients suffering from mucormycosis.

  14. Longitudinal Assessment of Hematopoietic Stem Cell Transplantation and Hyposalivation

    DEFF Research Database (Denmark)

    Laaksonen, Matti; Ramseier, Adrian; Rovó, Alicia

    2011-01-01

    Hyposalivation is a common adverse effect of anti-neoplastic therapy of head and neck cancer, causing impaired quality of life and predisposition to oral infections. However, data on the effects of hematopoietic stem cell transplantation (HSCT) on salivary secretion are scarce. The present study...

  15. 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...

  16. Bortezomib consolidation after autologous stem cell transplantation in multiple myeloma

    DEFF Research Database (Denmark)

    Mellqvist, Ulf-Henrik; Gimsing, Peter; Hjertner, Oyvind

    2013-01-01

    The Nordic Myeloma Study Group conducted an open randomized trial to compare bortezomib as consolidation therapy given after high-dose therapy and autologous stem cell transplantation (ASCT) with no consolidation in bortezomib-naive patients with newly diagnosed multiple myeloma. Overall, 370...

  17. 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...

  18. 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...

  19. WHAT UNRELATED HEMATOPOIETIC STEM CELL TRANSPLANTATION IN THALASSEMIA TAUGHT US ABOUT TRANSPLANT IMMUNOGENETICS.

    Directory of Open Access Journals (Sweden)

    Giorgio La Nasa

    2016-10-01

    Full Text Available Abstract Although the past few decades have shown an improvement in the survival and complication-free survival rates in patients with beta-thalassemia major and gene therapy is already at an advanced stage of experimentation, hematopoietic stem cell transplantation (HSCT continues to be the only effective and realistic approach to the cure of this chronic non-malignant disease. Historically, human leukocyte antigen (HLA-matched siblings have been the preferred source of donor cells owing to superior outcomes compared with HSCT from other sources. Nowadays, the availability of an international network of voluntary stem cell donor registries and cordon blood banks has significantly increased the odds of finding a suitable HLA matched donor. Stringent immunogenetic criteria for donor selection have made it possible to achieve overall survival (OS and thalassemia-free survival (TFS rates comparable to those of sibling transplants. However, acute and chronic graft-versus-host disease (GVHD remains the most important complication in unrelated HSCT in thalassemia, leading to considerable rates of morbidity and mortality for a chronic non-malignant disease. A careful immunogenetic assessment of donors and recipients makes it possible to individuate appropriate strategies for its prevention and management. This review provides an overview on recent insights about immunogenetic factors involved in GVHD, which seem to have a potential role in the outcome of transplantation for thalassemia.

  20. Cell Transplantation for Spinal Cord Injury: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Jun Li

    2013-01-01

    Full Text Available Cell transplantation, as a therapeutic intervention for spinal cord injury (SCI, has been extensively studied by researchers in recent years. A number of different kinds of stem cells, neural progenitors, and glial cells have been tested in basic research, and most have been excluded from clinical studies because of a variety of reasons, including safety and efficacy. The signaling pathways, protein interactions, cellular behavior, and the differentiated fates of experimental cells have been studied in vitro in detail. Furthermore, the survival, proliferation, differentiation, and effects on promoting functional recovery of transplanted cells have also been examined in different animal SCI models. However, despite significant progress, a “bench to bedside” gap still exists. In this paper, we comprehensively cover publications in the field from the last years. The most commonly utilized cell lineages were covered in this paper and specific areas covered include survival of grafted cells, axonal regeneration and remyelination, sensory and motor functional recovery, and electrophysiological improvements. Finally we also review the literature on the in vivo tracking techniques for transplanted cells.

  1. Transplantation? Peripheral Stem Cell/Bone Marrow/Cord Blood

    Directory of Open Access Journals (Sweden)

    Itır Sirinoglu Demiriz

    2012-01-01

    Full Text Available The introduction of peripheral stem cell (PSC and cord blood (CB as an alternative to bone marrow (BM recently has caused important changes on hematopoietic stem cell transplantation (HSCT practice. According to the CIBMTR data, there has been a significant decrease in the use of bone marrow and increase in the use of PSC and CB as the stem cell source for HSCT performed during 1997–2006 period for patients under the age of 20. On the other hand, the stem cell source in 70% of the HSCT procedures performed for patients over the age of 20 was PSC and the second most preferred stem cell source was bone marrow. CB usage is very limited for the adult population. Primary disease, stage, age, time and urgency of transplantation, HLA match between the patient and the donor, stem cell quantity, and the experience of the transplantation center are some of the associated factors for the selection of the appropriate stem cell source. Unfortunately, there is no prospective randomized study aimed to facilitate the selection of the correct source between CB, PSC, and BM. In this paper, we would like to emphasize the data on stem cell selection in light of the current knowledge for patient populations according to their age and primary disease.

  2. Hematopoietic Stem Cell Transplantation for Severe Combined Immunodeficiency

    Science.gov (United States)

    Wahlstrom, Justin T.; Dvorak, Christopher C.; Cowan, Morton J.

    2015-01-01

    Hematopoietic stem cell transplantation (HSCT) is an effective approach for the treatment of severe combined immunodeficiency (SCID). However, SCID is not a homogeneous disease, and the treatment required for successful transplantation varies significantly between SCID subtypes and the degree of HLA mismatch between the best available donor and the patient. Recent studies are beginning to more clearly define this heterogeneity and how outcomes may vary. With a more detailed understanding of SCID, new approaches can be developed to maximize immune reconstitution, while minimizing acute and long-term toxicities associated with chemotherapy conditioning. PMID:25821657

  3. ROLE AND TIMING OF HEMATOPOIETIC CELL TRANSPLANTATION FOR MYELODYSPLASTIC SYNDROME

    Directory of Open Access Journals (Sweden)

    Teresa L Field

    2010-07-01

    Full Text Available Allogeneic hematopoietic cell transplantation (HCT is the only curative treatment for patients with myelodysplastic syndromes (MDS.  Most patients with MDS are older than 60 years and age-associated morbidities limit the patients’ options for curative transplant therapy.  Since the development of conditioning regimens with reduced toxicity, the age limitations for HCT have waned for those patients with good performance status. This review will discuss the role of HCT for MDS based on prognostic features, the optimal timing of HCT, and outcomes based on patient age.

  4. Evaluation of transplantation of mesenchymal cells in acute myocardial infarction

    Directory of Open Access Journals (Sweden)

    Aliya Dzholdasbekova

    2012-12-01

    Full Text Available It has been studied in the pilot clinical research the effect of systemic (intravenous transplantation of mesenchymal stem cells (MSC of a bone marrow to 20 patients with an acute myocardial infarction with lifting segment of ST (STEMI carried out in the first 2 hours by percutaneous coronary intervention (PCI with stenting infarct related artery and the common course of drug therapy. It has been shown that the transplantation of MSCs had not caused any complications (allergic reactions, hazardous to health arrhythmias, embolism and heavy frustration of hemodynamic and had not lead to condition deterioration afterwards. In the first 3-6 months after systemic transplantation of MSCs to the patients’ heart contractive activity has been advanced which was clinically proved in the reduction of the heart failure level degree of expressiveness of warm insufficiency.

  5. Sexual health in hematopoietic stem cell transplant recipients.

    Science.gov (United States)

    Li, Zhuoyan; Mewawalla, Prerna; Stratton, Pamela; Yong, Agnes S M; Shaw, Bronwen E; Hashmi, Shahrukh; Jagasia, Madan; Mohty, Mohamad; Majhail, Navneet S; Savani, Bipin N; Rovó, Alicia

    2015-12-01

    Hematopoietic stem cell transplantation (HSCT) plays a central role in patients with malignant and, increasingly, nonmalignant conditions. As the number of transplants increases and the survival rate improves, long-term complications are important to recognize and treat to maintain quality of life. Sexual dysfunction is a commonly described but relatively often underestimated complication after HSCT. Conditioning regimens, generalized or genital graft-versus-host disease, medications, and cardiovascular complications as well as psychosocial problems are known to contribute significantly to physical and psychological sexual dysfunction. Moreover, it is often a difficult topic for patients, their significant others, and health care providers to discuss. Early recognition and management of sexual dysfunction after HSCT can lead to improved quality of life and outcomes for patients and their partners. This review focuses on the risk factors for and treatment of sexual dysfunction after transplantation and provides guidance concerning how to approach and manage a patient with sexual dysfunction after HSCT.

  6. A rat model for studying neural stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    Xue-mei ZHOU; Jing-bo SUN; Hui-ping YUAN; Dong-lai WU; Xin-rong ZHOU; Da-wei SUN; Hong-yi LI; Zheng-bo SHAO; Zhi-ren ZHANG

    2009-01-01

    Aim: The goal of this project was to develop a rat model for neural stem cell (NSC) transplantation studies in which NSCs were modified with brain-derived neurotrophic factor (BDNF) genes that may permit extensive and reliable analysis of the transplants. Methods: NSCs were cultured and purified by limiting dilution assay in vitro and infected with recombinant retrovirus pLXSN-BDNF (BDNF-NSCs) and retrovirus pLXSN (p-NSCs). The expression of BDNF genes in transgenic and control NSC groups was measured by FQ-PCR and ELISA assays. NSCs were then transplanted into the subretinal space of normal rat retinas in four groups, which included NSCs alone, BDNF-NSCs, phosphate buffered saline (PBS) control, and normal control. Survival, migration, and differentiation of dono-cells in host retinas were observed with optical coherence tomography (OCT), Heidelberg retina angiograph (HRA), and immunohis-tochemistry, respectively.Results: The results obtained by FQ-PCR demonstrated that the copy numbers of BDNF gene templates from BDNF-NSCs were the highest among the four groups (P<0.05). Consistent with the results of FQ-PCR, BDNF protein level from the supernatant of the BDNF-NSCs group was much higher than that of the other two groups (P<0.05) as suggested by the ELISA assays. HRA and OCT showed that graft cells could successfully survive. Immunohistochemical analysis revealed that transplanted BDNF-NSCs could migrate in the host retinas and differentiate into glial cells and neurons three months after transplantation. Conclusion: BDNF promotes NSCs to migrate and differentiate into neural cells in the normal host retinas.

  7. Clinical relevance of KIRs in hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Vojvodić Svetlana

    2010-01-01

    Full Text Available Introduction Natural Killer cells (NK cells represent the subset of peripheral lymphocytes that play critical role in the innate immune response to virus-infected and tumor transformed cells. Lysis of NK sensitived target cells could be mediated independently of antigen stimulation, and unlike cytotoxic T-lymphocytes, they do not require peptide presentation by the major histocompatibility complex (MHC molecules. NK cell cytotoxic activity is controlled by considerable number of cell surface Killer cell Immunoglobulin like Receptors (KIRs, which can exist in both inhibitory and activating isoforms. The inhibitory KIRs are mostly specific for HLA class I ligands and I HLA class like molecules, while the specificity of activating receptors is regarded to lectine-like superfamily. The role of NK cells in allogeneic haematopoietic stem cell transplantation (HSCT: NK cells are the first lymphocyte subset that reconstitute the peripheral blood following allogeneic HSCT. By selecting donors mismatched for relevant HLA ligands in the context of recipients KIR genotype, multiple roles for alloreactive donor NK cells have been demonstrated, in diminishing Graft vs. Host Disease (GvHD through selective killing of recipient dendritic cells, prevention of graft rejection by killing recipient T cells and participation in Graft vs. Leukaemia (GvL effect through destruction of residual host tumor cells. Conclusion Investigation of KIRs heterogenity play an important role in the field of HSCT, because it is useful for the early diagnosis of post transplant complications and can serve as a predictive risk factor for GvHD development.

  8. Hematopoietic progenitor cell mobilization for autologous transplantation - a literature review

    Directory of Open Access Journals (Sweden)

    Marco Aurélio Salvino

    2016-02-01

    Full Text Available ABSTRACT The use of high-dose chemotherapy with autologous support of hematopoietic progenitor cells is an effective strategy to treat various hematologic neoplasms, such as non-Hodgkin lymphomas and multiple myeloma. Mobilized peripheral blood progenitor cells are the main source of support for autologous transplants, and collection of an adequate number of hematopoietic progenitor cells is a critical step in the autologous transplant procedure. Traditional strategies, based on the use of growth factors with or without chemotherapy, have limitations even when remobilizations are performed. Granulocyte colony-stimulating factor is the most widely used agent for progenitor cell mobilization. The association of plerixafor, a C-X-C Chemokine receptor type 4 (CXCR4 inhibitor, to granulocyte colony stimulating factor generates rapid mobilization of hematopoietic progenitor cells. A literature review was performed of randomized studies comparing different mobilization schemes in the treatment of multiple myeloma and lymphomas to analyze their limitations and effectiveness in hematopoietic progenitor cell mobilization for autologous transplant. This analysis showed that the addition of plerixafor to granulocyte colony stimulating factor is well tolerated and results in a greater proportion of patients with non-Hodgkin lymphomas or multiple myeloma reaching optimal CD34+ cell collections with a smaller number of apheresis compared the use of granulocyte colony stimulating factor alone.

  9. Molecular imaging of stem cell transplantation for neurodegenerative diseases.

    Science.gov (United States)

    Wang, Ping; Moore, Anna

    2012-01-01

    Cell replacement therapy with stem cells holds tremendous therapeutic potential for treating neurodegenerative diseases. Over the last decade, molecular imaging techniques have proven to be of great value in tracking transplanted cells and assessing the therapeutic efficacy. This current review summarizes the role and capabilities of different molecular imaging modalities including optical imaging, nuclear imaging and magnetic resonance imaging in the field of stem cell therapy for neurodegenerative disorders. We discuss current challenges and perspectives of these techniques and encompass updated information such as theranostic imaging and optogenetics in stem cell-based treatment of neurodegenerative diseases.

  10. Transplantable NK cell progenitors in murine bone marrow.

    Science.gov (United States)

    Moore, T; Bennett, M; Kumar, V

    1995-02-15

    Differentiation of NK cells from pluripotent hematopoietic stem cells is a poorly understood process. Although it is known that NK cells are bone marrow derived and dependent upon an intact bone marrow microenvironment for complete maturation, it is not known if they arise from an intermediate lymphoid stem cell or from progenitors exclusively committed to the NK lineage. To determine whether phenotypically distinct committed NK progenitor cells exist in murine bone marrow, we sorted cells capable of repopulating recipient mice with mature NK cells upon i.v. transfer. We identified a rare population of bone marrow cells with the phenotype Ly6+ Lin- c-kit+ CD43high Fall-3high TSA-1- AA4.1low Rh123high that is highly enriched for the ability to generate NK cells after transplantation. Although these cells are relatively depleted of Rh123low pluripotent stem cells, they are highly enriched for both lymphoid and myeloid repopulating ability. Thus, we have found no evidence to support the existence of a phenotypically distinct transplantable progenitor population in mouse bone marrow that is either exclusively committed to the NK cell lineage or exhibits the functional characteristics of a common lymphoid stem cell.

  11. RESULTS OF HEMATOPOIETIC CELL TRANSPLANTATION IN PEDIATRIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    A. Mousavi

    2008-05-01

    Full Text Available Hematopoietic cell transplantation (HCT is an accepted treatment for acute myeloid leukemia (AML in first remission, the treatment of choice for chronic myeloid leukemia (CML and high risk groups of ALL who relapse with conventional chemotherapy. We assessed results of HCT for pediatric leukemia in our center. A total of 92 children, 63 with diagnose of AML, 23 with ALL and 6 with CML received allogeneic transplantation from HLA full matched siblings (57.6% and autologous transplantation (42.4%. Source of hematopoietic cells were peripheral blood 83.7%, bone marrow 15.2% and cord blood 1.6%. The median transplanted nucleated cells were 6.4 ± 4.7 ×108 /Kg (body weight of patients and mononuclear cells were 5.5 ± 2.9×108/Kg. The most common conditioning regimens were cyclophosphamide + busulfan. Prophylaxis regimen for GVHD was cyclosporin ± methotrexate. GVHD occurred in 50 (54.3% patients. Eighty five of children had engraftment, 26 (28.6% relapsed and 57 (62% are alive. The most common cause of death was relapse (68.6%. Five years overall survival of patients with AML and ALL were 49% and 44% respectively and disease free survival of them were 52% and 49%. One year overall survival and disease free survival of CML was 57%. Overall survival increased with increasing age of patients at transplantation time (P = 0.06. Longer survival significantly related to earlier WBC and platelet recovery (P < 0.0001 and P = 0.006 respectively. Considering acceptable overall and disease free survival of patients after HCT, we concluded that is a good modality in treatment of leukemia of children.

  12. Successful second transplantation from haploidentical donor for graft failure following unrelated cord blood cell transplantation or mismatched related transplantation: 2cases report

    Institute of Scientific and Technical Information of China (English)

    XU Lan-ping; HUANG Xiao-jun

    2006-01-01

    @@ Cord blood transplantation (CBT) from unrelated donors has increasingly been performed worldwide during the last decade. The immaturity of lymphocytes in cord blood permits HLA-mismatching between donors and recipients and reduces the severity of graft-versus-host disease (GVHD).However, the relatively small dose of the cord blood nucleated cells is associated with a high frequency of engraftment failure.1-5 But re-transplantation with stem cells from the original donor is impossible.

  13. Adipose derived stem cell transplantation is better than bone marrow mesenchymal stem cell transplantation in treating hindlimb ischemia in mice

    Directory of Open Access Journals (Sweden)

    Ngoc Bich Vu

    2016-09-01

    Full Text Available Introduction: Bone marrow derived MSCs (BM-MSCs and adipose derived MSCs (AD-MSCs are among the types of stem cells most commonly studied. Our study aims to compare the therapeutic efficacy of allograft AD-MSCs versus BM-MSCs in a mouse model of hindlimb ischemia. Methods: AD-MSCs were isolated from belly fat and BM-MSCs were isolated from femur bone marrow. They were used to treat mice with acute hindlimb ischemia. Treatment efficacy was compared among 4 groups: injected with BM-MSCs, injected with AD-MSCs, non-treated and injected with phosphate buffered saline. Mice in the groups were evaluated for the following: necrosis grade of leg, leg edema, blood flow, muscle cell restructure and new blood vessel formation. Results: Results showed that AD-MSC transplantation significantly recovered acute limb ischemia, with 76.5% of mice fully recovered, while the ratio was only 48.5% in BM-MSC transplanted group, and 0% in the non-treated and PBS groups. Evaluation of leg edema, blood flow, muscle cell restructure and new blood vessel formation also supported the observation that AD-MSC transplantation was superior over BM-MSC transplantation. Conclusion: Therefore, AD-MSCs may serve as the more suitable MSC for hindlimb ischemia treatment and angiogenesis therapy. [Biomed Res Ther 2016; 3(9.000: 844-856

  14. National Hematopoietic Stem Cells Transplant Registry in Poland: Nationwide Internet Reporting System and Results.

    Science.gov (United States)

    Łęczycka, A; Dudkiewicz, M; Czerwiński, J; Malanowski, P; Żalikowska-Hołoweńko, J; Danielewicz, R

    2016-06-01

    History of hematopoietic stem cell transplantations in Poland begins in early 1980s; the 1st bone marrow allotransplantation was performed in 1983 in the Central Clinical Hospital of the Military Medical Academy in Warsaw. Following years brought the 1st autologous stem cell transplantations. Ten years later, unrelated bone marrow transplantation was performed for the 1st time by the team of the Hematology and Blood and Marrow Transplantation Unit in Katowice. Since then, hematopoietic stem cell transplantation developed to be standard procedure and one of the most important therapies applied in leukemia treatment. The number of allotransplantations in Poland has grown significantly in the past 2 decades, which generated new needs and problems. In 2005, based on a new Transplant Law, a National Transplants Registry was created. Its main role is to collect data (registration of procedures and follow-up data) related to every transplantation case for stem cells and tissues as well as for organs. We present statistics concerning stem cell transplantations performed in Poland, as collected in the National Transplants Registry in the years 2006-2014. There are 18 centers transplanting hematopoietic stem cells in Poland. The total number of hematopoietic stem cell transplantations performed in 2006-2014 was 3,537, with allotransplantations from relatives accounted for 1,491 and from unrelated donors for 2,046. The main indication for allotransplantation in past years was acute leukemia.

  15. CD4+Foxp3+ regulatory T cell therapy in transplantation

    Institute of Scientific and Technical Information of China (English)

    Qizhi Tang; Jeffrey A. Bluestone; Sang-Mo Kang

    2012-01-01

    Regulatory T cells (Tregs) are long-lived cells that suppress immune responses in vivo in a dominant and antigen-specific manner.Therefore,therapeutic application of Tregs to control unwanted immune responses is an active area of investigation.Tregs can confer long-term protection against auto-inflammatory diseases in mouse models.They have also been shown to be effective in suppressing alloimmunity in models of graft-versus-host disease and organ transplantation.Building on extensive research in Treg biology and preclinical testing of therapeutic efficacy over the past decade,we are now at the point of evaluating the safety and efficacy of Treg therapy in humans.This review focuses on developing therapy for transplantation using CD4+Foxp3+ Tregs,with an emphasis on the studies that have informed clinical approaches that aim to maximize the benefits while overcoming the challenges and risks of Treg cell therapy.

  16. Treatment of systemic sclerosis: potential role for stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Wen Xiong

    2009-11-01

    Full Text Available Wen Xiong, Chris T DerkDivision of Rheumatology, Thomas Jefferson University, Philadelphia, PA, 19107, USAAbstract: Hematopoietic stem cell transplantation may “reset” the immune reconstitution and induce self tolerance of autoreactive lymphocytes, and has been explored in the treatments for systemic sclerosis. Phase I/II trials have shown a satisfactory risk benefit ratio. The true benefit will be identified by two ongoing prospective, randomized phase III trials. Multipotent mesenchymal stromal cells (MSCs possess antiproliferative, anti-inflammatory, and immunosuppressive properties. The use of MSCs has showed successful responses in patients with severe steroid-resistant acute graft versus host disease in phase II trials, and may be a potentially promising option for patients with systemic sclerosis.Keywords: scleroderma, systemic sclerosis, treatment, stem cells, transplant

  17. Adult stem cell transplantation in stroke: its limitations and prospects.

    Science.gov (United States)

    Roh, Jae-Kyu; Jung, Keun-Hwa; Chu, Kon

    2008-09-01

    A growing number of studies have demonstrated stem cell-based therapy provides a feasible, realistic approach to the restoration of lost brain function after stroke. Moreover, adult stem cells may provide more appropriate clinical strategies. Leading candidate sources include bone marrow, peripheral blood, adipose tissue, skeletal muscle, and olfactory mucosa, which act as central repositories for multipotent stem cells that can repopulate neural tissues. The medical society is currently enthusiastic concerning the clinical applications of autologous adult stem cells in stroke, based on promising results obtained during experimental studies and initial clinical trials. However, before embracing clinical applications, several essential precautions must be properly addressed. For example, the regenerative potentials of adult stem cells decline with age, and stem cells isolated from aged patients may retain dysfunctional characteristics. Are the natures and amounts of available autologous cells appropriate for therapeutic application in stroke? Do transplanted cells remain functional in the diseased brain, and if so what are the optimal injection routes, cell doses, and timings? Thus, we believe that success in future clinical trials will depend on careful investigation at the experimental level, to allow us to understand not only the practicalities of stem cell use, but also the underlying biological principles involved. Here, we review the advantages and disadvantages of the different adult stem cell sources and discuss the challenges that must be negotiated to achieve transplantation success.

  18. Bone marrow processing for transplantation using Cobe Spectra cell separator.

    Science.gov (United States)

    Veljković, Dobrila; Nonković, Olivera Šerbić; Radonjić, Zorica; Kuzmanović, Miloš; Zečević, Zeljko

    2013-06-01

    Concentration of bone marrow aspirates is an important prerequisite prior to infusion of ABO incompatible allogeneic marrow and prior to cryopreservation and storage of autologous marrow. In this paper we present our experience in processing 15 harvested bone marrow for ABO incompatible allogeneic and autologous bone marrow (BM) transplantation using Cobe Spectra® cell separator. BM processing resulted in the median recovery of 91.5% CD34+ cells, erythrocyte depletion of 91% and volume reduction of 81%. BM processing using cell separator is safe and effective technique providing high rate of erythrocyte depletion and volume reduction, and acceptable recovery of the CD34+ cells.

  19. Stem Cell Transplantation in Iran: A Systematic Review Article

    Directory of Open Access Journals (Sweden)

    Rowshanak ABBASI

    2015-10-01

    Full Text Available Background: Stem cell therapy is a new treatment option for different diseases. The aim of this systematic review is assessing the articles that focus on SCT in Iran and evaluate the amount of their success, failure and complication.Methods: Systematic search was conducted for finding English and Persian papers (controlled trials and cohort studies with follow up published before March 2015. We searched PubMed, ISI, and SCOPUS as the main international electronic data sources, as well as Iranmedex, Irandoc, andSID as the main domestic databases. Quality assessment of clinical trial and cohort study was performed based on the Consolidated Standards of Reporting Trials (CONSORT and the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE check lists respectively.Results: The 19 published articles in this systematic review included 2 cohort, 13 clinical trial, 3 open label clinical trial and 1 clinical trial pilot study. The stem cell types for transplantation were Mesenchymal (63.15%, mononuclear (31.6%, and fetal liver cell suspension (5.6%. The most SCT was performed at Tehran (68.42%, Shiraz (15.8%, Kerman & Isfahan hospitals (5.26%. The main diseases were decompensated cirrhosis and myocardial infarction (26.31%, MS (15.78%, DM (10.52%, Burger disease, neuroblastoma, sub-acute spinal cord injury and osteoarthritis (5.26%.Conclusion: The most of cells transplantation are performed successfully in Iran. Cell transplantation may be safely administered to treat patients with disabling disease. Keywords: Clinical Trial, Cohort, Stem Cell Transplantation, Iran

  20. Stem Cell Transplantation for Neuroprotection in Stroke

    Directory of Open Access Journals (Sweden)

    Cesar V. Borlongan

    2013-03-01

    Full Text Available Stem cell-based therapies for stroke have expanded substantially over the last decade. The diversity of embryonic and adult tissue sources provides researchers with the ability to harvest an ample supply of stem cells. However, the optimal conditions of stem cell use are still being determined. Along this line of the need for optimization studies, we discuss studies that demonstrate effective dose, timing, and route of stem cells. We recognize that stem cell derivations also provide uniquely individual difficulties and limitations in their therapeutic applications. This review will outline the current knowledge, including benefits and challenges, of the many current sources of stem cells for stroke therapy.

  1. TRANSPLANTATION

    Institute of Scientific and Technical Information of China (English)

    1996-01-01

    Objective: To explore the experience ofliver transpfantation in patients with terminalliver failure. Methods: From October 1991 toJuly 1995, 17 adults and 6 children underwentorthotopic liver transplantation. Preoperativediagnosis showed biliary atresia (n=5), Alagillesyndrome (n=1), primary biliary cirrhosis(n=2), cryptogenic cirrhosis (n=2), alcoholic

  2. Role of SDF1/CXCR4 Interaction in Experimental Hemiplegic Models with Neural Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Noboru Suzuki

    2012-02-01

    Full Text Available Much attention has been focused on neural cell transplantation because of its promising clinical applications. We have reported that embryonic stem (ES cell derived neural stem/progenitor cell transplantation significantly improved motor functions in a hemiplegic mouse model. It is important to understand the molecular mechanisms governing neural regeneration of the damaged motor cortex after the transplantation. Recent investigations disclosed that chemokines participated in the regulation of migration and maturation of neural cell grafts. In this review, we summarize the involvement of inflammatory chemokines including stromal cell derived factor 1 (SDF1 in neural regeneration after ES cell derived neural stem/progenitor cell transplantation in mouse stroke models.

  3. Skin Cancer Risk in Hematopoietic Stem-Cell Transplant Recipients Compared With Background Population and Renal Transplant Recipients

    DEFF Research Database (Denmark)

    Omland, Silje Haukali; Gniadecki, Robert; Hædersdal, Merete

    2016-01-01

    IMPORTANCE: While a high risk of nonmelanoma skin cancer is well recognized in solid-organ transplant recipients, the risk of skin cancer in hematopoietic stem-cell transplant (HSCT) recipients has not been extensively studied. OBJECTIVE: To determine the risk of cutaneous cancer in HSCT recipients...... and compare it with the risk in renal transplant recipients (RTRs) and individuals who have not received any transplant. DESIGN, SETTING, AND PARTICIPANTS: A nationwide population-based cohort study from the Danish National Hospital Register including 3302 patients who underwent HSCT (1007 allogeneic, 2295...... cancer between transplant recipients and background population, we used a stratified proportional hazard regression model for hazard ratio (HR) estimations. By use of the cumulative incidence, we estimated 5- and 10-year risks of skin cancers. All RTR and HSCT recipients were treated and followed up...

  4. Hypomethylating agents after allogeneic blood stem cell transplantation

    Science.gov (United States)

    Rautenberg, Christina; Haas, Rainer; Kobbe, Guido

    2016-01-01

    Allogeneic blood stem cell transplantation (allo-SCT) is a potentially curative treatment for patients with myeloid malignancies such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), but relapse remains the major cause of treatment failure. So far, therapeutic options for patients with AML or MDS who relapse after allo-SCT generally consisted of palliative care, low-dose or intensive chemotherapy as well as cellular therapies such as donor lymphocyte infusions (DLI) and second transplantation in selected cases. Nevertheless, the prognosis of patients with myeloid malignancies relapsing after allo-SCT remains dismal therefore asking for novel treatment strategies. Considering their well-balanced profile of good efficacy and moderate toxicity in the non-transplant setting, the hypomethylating agents (HMA) azacitidine (Aza) and decitabine (DAC) have also been tested either alone or in combination with DLI in the post-transplant period. This review summarizes the current knowledge about the use of these two HMA as pre-emptive, salvage or consolidation therapy mostly retrieved from retrospective studies but also from a few prospective trials. Within this review, we also comment on some practical issues such as optimal dose and schedule, the choice of HMA candidates and the role of additional cellular interventions. Finally, we also give an overview on the assumed mode of actions, ongoing research, clinical studies and potential combination partners aiming to improve this treatment approach. PMID:28066786

  5. Epigenetic therapy in allogeneic hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Qaiser Bashir

    2013-01-01

    Full Text Available DNA methylation and other epigenetic phenomena appear to be relevant in the pathogenesis of several malignant disorders. DNA methyltransferases add methyl groups to cytosine-phosphate-guanine (CpG islandsleading to gene promoter silencing. The DNA methyltransferases inhibitors azacitidine and decitabine have anti-tumor activity against a broad range of malignancies, but have been investigated mostly in myelodysplastic syndrome. In addition, these agents have immunomodulatory effects that are under investigation in the allogeneic stem cell transplantation scenario. Both drugs have been used in the perioperative period of allogeneic transplantations with varying degrees of success. It has been hypothesized that low dose azacitidine may increase the graftversus-leukemia effect and have a role in the maintenance of remission after allogeneic transplantation for myeloid leukemias. It is also intriguing that this favorable effect might occur while mitigating graft-versus-host disease. Here we present a review of the rapidly growing field of epigenetic manipulation using hypomethylating agents in allogeneic transplantation.

  6. Rhizomucor and Scedosporium Infection Post Hematopoietic Stem-Cell Transplant

    Directory of Open Access Journals (Sweden)

    Dânia Sofia Marques

    2011-01-01

    Full Text Available Hematopoietic stem-cell transplant recipients are at increased risk of developing invasive fungal infections. This is a major cause of morbidity and mortality. We report a case of a 17-year-old male patient diagnosed with severe idiopathic acquired aplastic anemia who developed fungal pneumonitis due to Rhizomucor sp. and rhinoencephalitis due to Scedosporium apiospermum 6 and 8 months after undergoing allogeneic hematopoietic stem-cell transplant from an HLA-matched unrelated donor. Discussion highlights risk factors for invasive fungal infections (i.e., mucormycosis and scedosporiosis, its clinical features, and the factors that must be taken into account to successfully treat them (early diagnosis, correction of predisposing factors, aggressive surgical debridement, and antifungal and adjunctive therapies.

  7. Chlamydia pneumoniae respiratory infection after allogeneic stem cell transplantation.

    Science.gov (United States)

    Geisler, William M; Corey, Lawrence

    2002-03-27

    Chlamydia pneumoniae is a common cause of upper and lower respiratory tract infections in immunocompetent patients; however, its role as a respiratory pathogen in immunocompromised hosts has been infrequently recognized. We describe C. pneumoniae lower respiratory tract infection in a 19-year-old male after allogeneic stem cell transplantation. The patient developed fever on day +14, and a subsequent computed tomography scan of the chest revealed a right lateral pleural-based opacity, which was then resected during thoracoscopy. Diagnosis was made by culture and staining of the resected tissue with C. pneumoniae-specific monoclonal antibodies, and azithromycin was administered. To the best of our knowledge, this is the first report of C. pneumoniae respiratory infection after stem cell or marrow transplantation. C. pneumoniae often coexists with other etiologic agents of pneumonia in immunocompromised patients. Considering the infrequency of infections from this organism in this clinical setting, one must still rule out other more likely respiratory pathogens.

  8. Fecal microbiota transplantation for fulminant Clostridium difficile infection in an allogeneic stem cell transplant patient.

    Science.gov (United States)

    Neemann, K; Eichele, D D; Smith, P W; Bociek, R; Akhtari, M; Freifeld, A

    2012-12-01

    We present a case of severe Clostridium difficile infection (CDI) in a non-neutropenic allogeneic hematopoietic stem cell transplant recipient who was treated successfully with fecal microbiota therapy after standard pharmacologic therapy had failed. Following naso-jejunal instillation of donor stool, the patient's symptoms resolved within 48 h. Bowel resection was averted. This is the first case in the literature, to our knowledge, to describe fecal microbiota therapy in a profoundly immunocompromised host with severe CDI. We propose that fecal microbiota therapy be considered as a therapeutic option in immunosuppressed patients with refractory severe CDI.

  9. Intestinal dysbiosis and allogeneic hematopoietic progenitor cell transplantation

    OpenAIRE

    Raghunathan, Vikram M.; Sheng, Iris; Lim, Seah H.

    2016-01-01

    The intestinal microbiota is a diverse and dynamic ecosystem that is increasingly understood to play a vital role in human health. Hematopoietic stem cell transplant recipients undergo prolonged exposure to antimicrobials, chemotherapeutic agents, and immunosuppressants, resulting in profound shifts in the gut microbiome. A growing body of research has revealed the ways in which these microbiologic shifts shape immune modulation, affecting susceptibility to infections and graft-versus-host di...

  10. Treatment of systemic sclerosis: potential role for stem cell transplantation

    OpenAIRE

    Wen Xiong; Derk, Chris T.

    2009-01-01

    Wen Xiong, Chris T DerkDivision of Rheumatology, Thomas Jefferson University, Philadelphia, PA, 19107, USAAbstract: Hematopoietic stem cell transplantation may “reset” the immune reconstitution and induce self tolerance of autoreactive lymphocytes, and has been explored in the treatments for systemic sclerosis. Phase I/II trials have shown a satisfactory risk benefit ratio. The true benefit will be identified by two ongoing prospective, randomized phase III trials. Multipo...

  11. Transplanting Retinal Cells using Bucky Paper for Support

    Science.gov (United States)

    Loftus, David J.; Cinke, Martin; Meyyappan, Meyya; Fishman, Harvey; Leng, Ted; Huie, Philip; Bilbao, Kalayaan

    2004-01-01

    A novel treatment for retinal degenerative disorders involving transplantation of cells into the eye is currently under development at NASA Ames Research Center and Stanford University School of Medicine. The technique uses bucky paper as a support material for retinal pigment epithelial (RPE) cells, iris pigment epithelial (IPE) cells, and/or stem cells. This technology is envisioned as a treatment for age-related macular degeneration, which is the leading cause of blindness in persons over age 65 in Western nations. Additionally, patients with other retinal degenerative disorders, such as retinitis pigmentosa, may be treated by this strategy. Bucky paper is a mesh of carbon nanotubes (CNTs), as shown in Figure 1, that can be made from any of the commercial sources of CNTs. Bucky paper is biocompatible and capable of supporting the growth of biological cells. Because bucky paper is highly porous, nutrients, oxygen, carbon dioxide, and waste can readily diffuse through it. The thickness, density, and porosity of bucky paper can be tailored in manufacturing. For transplantation of cells into the retina, bucky paper serves simultaneously as a substrate for cell growth and as a barrier for new blood vessel formation, which can be a problem in the exudative type of macular degeneration. Bucky paper is easily handled during surgical implantation into the eye. Through appropriate choice of manufacturing processes, bucky paper can be made relatively rigid yet able to conform to the retina when the bucky paper is implanted. Bucky paper offers a distinct advantage over other materials that have been investigated for retinal cell transplantation - lens capsule and Descemet's membrane - which are difficult to handle during surgery because they are flimsy and do not stay flat.

  12. System for tracking transplanted limbal epithelial stem cells in the treatment of corneal stem cell deficiency

    Science.gov (United States)

    Boadi, J.; Sangwal, V.; MacNeil, S.; Matcher, S. J.

    2015-03-01

    The prevailing hypothesis for the existence and healing of the avascular corneal epithelium is that this layer of cells is continually produced by stem cells in the limbus and transported onto the cornea to mature into corneal epithelium. Limbal Stem Cell Deficiency (LSCD), in which the stem cell population is depleted, can lead to blindness. LSCD can be caused by chemical and thermal burns to the eye. A popular treatment, especially in emerging economies such as India, is the transplantation of limbal stem cells onto damaged limbus with hope of repopulating the region. Hence regenerating the corneal epithelium. In order to gain insights into the success rates of this treatment, new imaging technologies are needed in order to track the transplanted cells. Optical Coherence Tomography (OCT) is well known for its high resolution in vivo images of the retina. A custom OCT system has been built to image the corneal surface, to investigate the fate of transplanted limbal stem cells. We evaluate two methods to label and track transplanted cells: melanin labelling and magneto-labelling. To evaluate melanin labelling, stem cells are loaded with melanin and then transplanted onto a rabbit cornea denuded of its epithelium. The melanin displays strongly enhanced backscatter relative to normal cells. To evaluate magneto-labelling the stem cells are loaded with magnetic nanoparticles (20-30nm in size) and then imaged with a custom-built, magneto-motive OCT system.

  13. Transplantation of Reprogrammed Autologous Stem Cells for Chronic Pain and Drug Abuse

    Science.gov (United States)

    2015-10-01

    AWARD NUMBER: W81XWH-11-1-0673 TITLE: Transplantation of Reprogrammed Autologous Stem Cells for Chronic Pain and Drug Abuse PRINCIPAL...CONTRACT NUMBER Transplantation of Reprogrammed Autologous Stem Cells for Chronic Pain and Drug Abuse 5b. GRANT NUMBER: W81XWH-11-1-0673 5c. PROGRAM...Tolerance, Drug abuse , Cell cultures, Spinal transplantation of autologous stem cells, Animal behavioral tests 16. SECURITY CLASSIFICATION OF: 17

  14. Alefacept and Allogeneic Hematopoietic Stem Cell Transplantation

    Science.gov (United States)

    2016-04-26

    Thalassemia; Sickle Cell Disease; Glanzmann Thrombasthenia; Wiskott-Aldrich Syndrome; Chronic-granulomatous Disease; Severe Congenital Neutropenia; Leukocyte Adhesion Deficiency; Schwachman-Diamond Syndrome; Diamond-Blackfan Anemia; Fanconi Anemia; Dyskeratosis-congenita; Chediak-Higashi Syndrome; Severe Aplastic Anemia

  15. Feasibility study of marrow stromal cells transplantation into guinea pig cochlea

    Institute of Scientific and Technical Information of China (English)

    GE Sheng-lei; XIE Ding-hua; CHEN Zhu-chu; XIAO Zhi-qiang; YANG Xin-min

    2005-01-01

    Objective This pilot-study was designed to evaluate the feasibility of cell transplantation into guinea pig cochlea. Methods Marrow stromal cells were labeled with DAPI, and then implanted into the cochlea of guinea pig.The existence and differentiation trend were observed roughly two weeks later by histologic analysis. Results Transplant-derived marrow stem cells survived in cochlea two weeks later with a trend of attaching to cochlear architecture but not differentiate into neuron. Conclusions Transplant-derived marrow stem cells can survive in cochlea,and cell transplantation may be a useful strategy in inner ear diseases.

  16. 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.

  17. Peripheral stem cell transplantation in non-Hodgkin's lymphoma patients.

    Science.gov (United States)

    Kessinger, A; Vose, J M; Bierman, P J; Bishop, M; Armitage, J O

    1993-01-01

    Transplantation of circulating progenitor/stem cells collected before and stored during administration of marrow-ablative antitumor therapy has restored sustained hematopoiesis for patients with a variety of malignancies. One of the most common diseases so treated is refractory or relapsed non-Hodgkin's lymphoma (NHL). Autologous peripheral stem cell transplantation (PSCT) often has been used rather than autologous bone marrow transplantation (ABMT) because NHL commonly involves the bone marrow, and because, in some situations, PSCT provides earlier engraftment than ABMT. Between July 1986 and September 1992, 170 adult patients with refractory or relapsed NHL were treated with high-dose therapy and PSCT at the University of Nebraska Medical Center (UNMC). With a median follow-up of 469 days for the evaluable survivors, the actuarial progression-free survival for 167 patients at 6 years after PSCT was 30%. High-dose therapy and PSCT for NHL patients has resulted in long-term progression-free survival and probably cure for some patients. The role of PSCT in this disease continues to evolve.

  18. Folate antagonist, methotrexate induces neuronal differentiation of human embryonic stem cells transplanted into nude mouse retina.

    Science.gov (United States)

    Hara, Akira; Taguchi, Ayako; Aoki, Hitomi; Hatano, Yuichiro; Niwa, Masayuki; Yamada, Yasuhiro; Kunisada, Takahiro

    2010-06-25

    Transplanted embryonic stem (ES) cells can be integrated into the retinas of adult mice as well-differentiated neuroretinal cells. However, the transplanted ES cells also have a tumorigenic activity as they have the ability for multipotent differentiation to various types of tissues. In the present study, human ES (hES) cells were transplanted into adult nude mouse retinas by intravitreal injections 20 h after intravitreal N-methyl-D-aspartate (NMDA) administration. After the transplantation of hES cells, the folate antagonist, methotrexate (MTX) was administrated in order to control the differentiation of the transplanted hES cells. Neuronal differentiation and teratogenic potential of hES cells were examined immunohistochemically 5 weeks after transplantation. The proliferative activity of transplanted cells was determined by both the mitotic index and the Ki-67 proliferative index. Disappearance of Oct-4-positive hES cells showing undifferentiated morphology was observed after intraperitoneal MTX treatment daily, for 15 days. Decreased mitotic and Ki-67 proliferative indices, and increased neuronal differentiation were detected in the surviving hES cells after the MTX treatment. These results suggest two important effects of intraperitoneal MTX treatment for hES cells transplanted into nude mouse retina: (1) MTX treatment following transplantation induces neuronal differentiation, and (2) MTX decreases proliferative activity and tumorigenic potential.

  19. Gastrointestinal Complications Following Hematopoietic Stem Cell Transplantation in Children

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ji Hye; Lim, Gye Yeon; Im, Soo Ah; Chung, Nak Gyun; Hahn, Seung Tae [St. Mary' s Hospital, The Catholic University of Korea, Seoul (Korea, Republic of)

    2008-10-15

    Gastrointestinal system involvement is one of the principal complications seen in the recipients of hematopoietic stem cell transplantation (HSCT), and it is also a major cause of morbidity and death in these patients. The major gastrointestinal complications include typhlitis (neutropenic enterocolitis), pseudomembranous enterocolitis, viral enteritis, graft-versus-host disease, benign pneumatosis intestinalis, intestinal thrombotic microangiopathy, and post-transplantation lymphoproliferative disease. As these patients present with nonspecific abdominal symptoms, evaluation with using such imaging modalities as ultrasonography and CT is essential in order to assess the extent of gastrointestinal involvement and to diagnose these complications. We present here a pictorial review of the imaging features and other factors involved in the diagnosis of these gastrointestinal complications in pediatric HSCT recipients.

  20. Antifungal prophylaxis following reduced-intensity stem cell transplantation.

    Science.gov (United States)

    Kami, M; Murashige, N; Tanaka, Y; Narimatsu, H

    2006-12-01

    Reduced-intensity stem cell transplantation (RIST) has been developed to be a novel curative option for advanced hematologic diseases. Its minimal toxicity allows for transplantation in patients with advanced age or with organ dysfunction. Young patients without comorbidity can undergo RIST as outpatients. However, fungal infection remains an important complication in RIST. Given the poor prognosis of fungal infection, prophylaxis is critical in its management. The prophylactic strategy is recently changing with the development of RIST. Hospital equipment is important for fungal prophylaxis; however, the median day for the development of fungal infection is day 100, when most RIST patients are followed as outpatients. The focus of fungal management after RIST needs to shift from in-hospital equipment to oral antifungals. Various antifungals have recently been developed and introduced for clinical use. A major change in antifungal management will probably occur within several years.

  1. Hematopoietic Stem Cell Transplantation in Adult Sickle Cell Disease: Problems and Solutions

    Directory of Open Access Journals (Sweden)

    Hakan Özdoğu

    2015-09-01

    Full Text Available Sickle cell disease-related organ injuries cannot be prevented despite hydroxyurea use, infection prophylaxis, and supportive therapies. As a consequence, disease-related mortality reaches 14% in adolescents and young adults. Hematopoietic stem cell transplantation is a unique curative therapeutic approach for sickle cell disease. Myeloablative allogeneic hematopoietic stem cell transplantation is curative for children with sickle cell disease. Current data indicate that long-term disease-free survival is about 90% and overall survival about 95% after transplantation. However, it is toxic in adults due to organ injuries. In addition, this curative treatment approach has several limitations, such as difficulties to find donors, transplant-related mortality, graft loss, graft-versus-host disease (GVHD, and infertility. Engraftment effectivity and toxicity for transplantations performed with nonmyeloablative reduced-intensity regimens in adults are being investigated in phase 1/2 trials at many centers. Preliminary data indicate that GVHD could be prevented with transplantations performed using reduced-intensity regimens. It is necessary to develop novel regimens to prevent graft loss and reduce the risk of GVHD.

  2. The Cell Biology of Cytomegalovirus: Implications for Transplantation.

    Science.gov (United States)

    Kaminski, H; Fishman, J A

    2016-08-01

    Interpretation of clinical data regarding the impact of cytomegalovirus (CMV) infection on allograft function is complicated by the diversity of viral strains and substantial variability of cellular receptors and viral gene expression in different tissues. Variation also exists in nonspecific (monocytes and dendritic cells) and specific (NK cells, antibodies) responses that augment T cell antiviral activities. Innate immune signaling pathways and expanded pools of memory NK cells and γδ T cells also serve to amplify host responses to infection. The clinical impact of specific memory T cell anti-CMV responses that cross-react with graft antigens and alloantigens is uncertain but appears to contribute to graft injury and to the abrogation of allograft tolerance. These responses are modified by diverse immunosuppressive regimens and by underlying host immune deficits. The impact of CMV infection on the transplant recipient reflects cellular changes and corresponding host responses, the convergence of which has been termed the "indirect effects" of CMV infection. Future studies will clarify interactions between CMV infection and allograft injury and will guide interventions that may enhance clinical outcomes in transplantation.

  3. Early Natural Killer Cell Reconstitution Predicts Overall Survival in T Cell-Replete Allogeneic Hematopoietic Stem Cell Transplantation

    DEFF Research Database (Denmark)

    Minculescu, Lia; Marquart, Hanne Vibeke; Friis, Lone Smidstrup

    2016-01-01

    Early immune reconstitution plays a critical role in clinical outcome after allogeneic hematopoietic stem cell transplantation (HSCT). Natural killer (NK) cells are the first lymphocytes to recover after transplantation and are considered powerful effector cells in HSCT. We aimed to evaluate...... the clinical impact of early NK cell recovery in T cell-replete transplant recipients. Immune reconstitution was studied in 298 adult patients undergoing HSCT for acute myeloid leukemia, acute lymphoblastic leukemia, and myelodysplastic syndrome from 2005 to 2013. In multivariate analysis NK cell numbers...... on day 30 (NK30) > 150 cells/µL were independently associated with superior overall survival (hazard ratio, .79; 95% confidence interval, .66 to .95; P = .01). Cumulative incidence analyses showed that patients with NK30 > 150 cells/µL had significantly less transplant-related mortality (TRM), P = .01...

  4. In vivo prevention of transplant arteriosclerosis by ex vivo-expanded human regulatory T cells.

    Science.gov (United States)

    Nadig, Satish N; Wieckiewicz, Joanna; Wu, Douglas C; Warnecke, Gregor; Zhang, Wei; Luo, Shiqiao; Schiopu, Alexandru; Taggart, David P; Wood, Kathryn J

    2010-07-01

    Transplant arteriosclerosis is the hallmark of chronic allograft dysfunction (CAD) affecting transplanted organs in the long term. These fibroproliferative lesions lead to neointimal thickening of arteries in all transplanted allografts. Luminal narrowing then leads to graft ischemia and organ demise. To date, there are no known tolerance induction strategies that prevent transplant arteriosclerosis. Therefore, we designed this study to test the hypothesis that human regulatory T cells (T(reg) cells) expanded ex vivo can prevent transplant arteriosclerosis. Here we show the comparative capacity of T(reg) cells, sorted via two separate strategies, to prevent transplant arteriosclerosis in a clinically relevant chimeric humanized mouse system. We found that the in vivo development of transplant arteriosclerosis in human arteries was prevented by treatment of ex vivo-expanded human T(reg) cells. Additionally, we show that T(reg) cells sorted on the basis of low expression of CD127 provide a more potent therapy to conventional T(reg) cells. Our results demonstrate that human T(reg) cells can inhibit transplant arteriosclerosis by impairing effector function and graft infiltration. We anticipate our findings to serve as a foundation for the clinical development of therapeutics targeting transplant arteriosclerosis in both allograft transplantation and other immune-mediated causes of vasculopathy.

  5. Regeneration of adenovirus specific T-cells after allogeneic, hematopietic stem cell transplantation in children and adolescents

    OpenAIRE

    2010-01-01

    Adenovirus is a significant cause of morbidity and mortality in pediatric allogeneic hematopoietic stem cell transplant recipients, and control of infection seems to require antigen-specific T cells. Aim of this Work was to estimate the Regeneration of Adenovirus-specific T-cells In 26 children (Age 8 months -25 years) over 6 months after HSCT and to investigate the effects of the transplantations parameter, Virus reactivation and the Transplantations complications on the adv-specific cell...

  6. Bioluminescence tracking of alginate micro-encapsulated cell transplants.

    Science.gov (United States)

    Tiernan, Aubrey R; Sambanis, Athanassios

    2017-02-01

    Cell-based therapies to treat loss-of-function hormonal disorders such as diabetes and Parkinson's disease are routinely coupled with encapsulation strategies, but an understanding of when and why grafts fail in vivo is lacking. Consequently, investigators cannot clearly define the key factors that influence graft success. Although bioluminescence is a popular method to track the survival of free cells transplanted in preclinical models, little is known of the ability to use bioluminescence for real-time tracking of microencapsulated cells. Furthermore, the impact that dynamic imaging distances may have, due to freely-floating microcapsules in vivo, on cell survival monitoring is unknown. This work addresses these questions by applying bioluminescence to a pancreatic substitute based on microencapsulated cells. Recombinant insulin-secreting cells were transduced with a luciferase lentivirus and microencapsulated in Ba(2+) crosslinked alginate for in vitro and in vivo studies. In vitro quantitative bioluminescence monitoring was possible and viable microencapsulated cells were followed in real time under both normoxic and anoxic conditions. Although in vivo dispersion of freely-floating microcapsules in the peritoneal cavity limited the analysis to a qualitative bioluminescence evaluation, signals consistently four orders of magnitude above background were clear indicators of temporal cell survival. Strong agreement between in vivo and in vitro cell proliferation over time was discovered by making direct bioluminescence comparisons between explanted microcapsules and parallel in vitro cultures. Broader application of this bioluminescence approach to retrievable transplants, in supplement to currently used end-point physiological tests, could improve understanding and accelerate development of cell-based therapies for critical clinical applications. Copyright © 2014 John Wiley & Sons, Ltd.

  7. NK Cells and Other Innate Lymphoid Cells in Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Vacca, Paola; Montaldo, Elisa; Croxatto, Daniele; Moretta, Francesca; Bertaina, Alice; Vitale, Chiara; Locatelli, Franco; Mingari, Maria Cristina; Moretta, Lorenzo

    2016-01-01

    Natural killer (NK) cells play a major role in the T-cell depleted haploidentical hematopoietic stem cell transplantation (haplo-HSCT) to cure high-risk leukemias. NK cells belong to the expanding family of innate lymphoid cells (ILCs). At variance with NK cells, the other ILC populations (ILC1/2/3) are non-cytolytic, while they secrete different patterns of cytokines. ILCs provide host defenses against viruses, bacteria, and parasites, drive lymphoid organogenesis, and contribute to tissue remodeling. In haplo-HSCT patients, the extensive T-cell depletion is required to prevent graft-versus-host disease (GvHD) but increases risks of developing a wide range of life-threatening infections. However, these patients may rely on innate defenses that are reconstituted more rapidly than the adaptive ones. In this context, ILCs may represent important players in the early phases following transplantation. They may contribute to tissue homeostasis/remodeling and lymphoid tissue reconstitution. While the reconstitution of NK cell repertoire and its role in haplo-HSCT have been largely investigated, little information is available on ILCs. Of note, CD34(+) cells isolated from different sources of HSC may differentiate in vitro toward various ILC subsets. Moreover, cytokines released from leukemia blasts (e.g., IL-1β) may alter the proportions of NK cells and ILC3, suggesting the possibility that leukemia may skew the ILC repertoire. Further studies are required to define the timing of ILC development and their potential protective role after HSCT.

  8. Hematopoietic cell transplantation for Crohn's disease; is it time?

    Institute of Scientific and Technical Information of China (English)

    Y Leung; M Geddes; J Storek; R Panaccione; PL Beck

    2006-01-01

    AIM: To review all studies in the literature that have assessed Hematopoietic cell transplantation (HCT)and Crohn's disease (CD) with the ultimate aims of determining if this is a viable treatment option for those with CD. A secondary aim was to review the above literature and determine if the studies shed further light on the mechanisms involved in the pathogenesis of CD.METHODS: An extensive Medline search was performed on all articles from 1970 to 2005 using the keywords;bone marrow transplant, stem cell, hematopoietic cell,Crohn's disease and inflammatory bowel disease.RESULTS: We identified one case in which a patient developed CD following an allogeneic HCT from a sibling suffering with CD. Evidence for transfer of the genetic predisposition to develop CD was also identified with report of a patient that developed severe CD following an allogeneic HCT. Following HCT it was found that the donor (that had no signs or symptoms of CD) and the recipient had several haplotype mismatches in HLA class Ⅲ genes in the IBD3 locus including a polymorphism of NOD2/CARD15 that has been associated with CD.Thirty three published cases of patients with CD who underwent either autologous or allogeneic HCT were identified. At the time of publication 29 of these 33patients were considered to be in remission. The median follow-up time was seven years, and twenty months for allogeneic and autologous HCT respectively. For patients who underwent HCT primarily for treatment of their CD there have been no mortalities related to transplant complications.CONCLUSION: Overall these preliminary data suggest that both allogeneic and autologous HCT may be effective in inducing remission in refractory CD. This supports the hypothesis that the hematolymphatic cells play a key role in CD and that resetting of the immune system may be a critical approach in the management or cure of CD.

  9. Hematopoietic Cell Transplantation Outcomes in Monosomal Karyotype Myeloid Malignancies.

    Science.gov (United States)

    Pasquini, Marcelo C; Zhang, Mei-Jie; Medeiros, Bruno C; Armand, Philippe; Hu, Zhen-Huan; Nishihori, Taiga; Aljurf, Mahmoud D; Akpek, Görgün; Cahn, Jean-Yves; Cairo, Mitchell S; Cerny, Jan; Copelan, Edward A; Deol, Abhinav; Freytes, César O; Gale, Robert Peter; Ganguly, Siddhartha; George, Biju; Gupta, Vikas; Hale, Gregory A; Kamble, Rammurti T; Klumpp, Thomas R; Lazarus, Hillard M; Luger, Selina M; Liesveld, Jane L; Litzow, Mark R; Marks, David I; Martino, Rodrigo; Norkin, Maxim; Olsson, Richard F; Oran, Betul; Pawarode, Attaphol; Pulsipher, Michael A; Ramanathan, Muthalagu; Reshef, Ran; Saad, Ayman A; Saber, Wael; Savani, Bipin N; Schouten, Harry C; Ringdén, Olle; Tallman, Martin S; Uy, Geoffrey L; Wood, William A; Wirk, Baldeep; Pérez, Waleska S; Batiwalla, Minoo; Weisdorf, Daniel J

    2016-02-01

    The presence of monosomal karyotype (MK+) in acute myeloid leukemia (AML) is associated with dismal outcomes. We evaluated the impact of MK+ in AML (MK+AML, n = 240) and in myelodysplastic syndrome (MDS) (MK+MDS, n = 221) on hematopoietic cell transplantation outcomes compared with other cytogenetically defined groups (AML, n = 3360; MDS, n = 1373) as reported to the Center for International Blood and Marrow Transplant Research from 1998 to 2011. MK+ AML was associated with higher disease relapse (hazard ratio, 1.98; P < .01), similar transplantation-related mortality (TRM) (hazard ratio, 1.01; P = .90), and worse survival (hazard ratio, 1.67; P < .01) compared with those outcomes for other cytogenetically defined AML. Among patients with MDS, MK+ MDS was associated with higher disease relapse (hazard ratio, 2.39; P < .01), higher TRM (hazard ratio, 1.80; P < .01), and worse survival (HR, 2.02; P < .01). Subset analyses comparing chromosome 7 abnormalities (del7/7q) with or without MK+ demonstrated higher mortality for MK+ disease in for both AML (hazard ratio, 1.72; P < .01) and MDS (hazard ratio, 1.79; P < .01). The strong negative impact of MK+ in myeloid malignancies was observed in all age groups and using either myeloablative or reduced-intensity conditioning regimens. Alternative approaches to mitigate disease relapse in this population are needed.

  10. Secondary solid cancer screening following hematopoietic cell transplantation.

    Science.gov (United States)

    Inamoto, Y; Shah, N N; Savani, B N; Shaw, B E; Abraham, A A; Ahmed, I A; Akpek, G; Atsuta, Y; Baker, K S; Basak, G W; Bitan, M; DeFilipp, Z; Gregory, T K; Greinix, H T; Hamadani, M; Hamilton, B K; Hayashi, R J; Jacobsohn, D A; Kamble, R T; Kasow, K A; Khera, N; Lazarus, H M; Malone, A K; Lupo-Stanghellini, M T; Margossian, S P; Muffly, L S; Norkin, M; Ramanathan, M; Salooja, N; Schoemans, H; Wingard, J R; Wirk, B; Wood, W A; Yong, A; Duncan, C N; Flowers, M E D; Majhail, N S

    2015-08-01

    Hematopoietic stem cell transplant (HCT) recipients have a substantial risk of developing secondary solid cancers, particularly beyond 5 years after HCT and without reaching a plateau overtime. A working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal to facilitate implementation of cancer screening appropriate to HCT recipients. The working group reviewed guidelines and methods for cancer screening applicable to the general population and reviewed the incidence and risk factors for secondary cancers after HCT. A consensus approach was used to establish recommendations for individual secondary cancers. The most common sites include oral cavity, skin, breast and thyroid. Risks of cancers are increased after HCT compared with the general population in skin, thyroid, oral cavity, esophagus, liver, nervous system, bone and connective tissues. Myeloablative TBI, young age at HCT, chronic GVHD and prolonged immunosuppressive treatment beyond 24 months were well-documented risk factors for many types of secondary cancers. All HCT recipients should be advised of the risks of secondary cancers annually and encouraged to undergo recommended screening based on their predisposition. Here we propose guidelines to help clinicians in providing screening and preventive care for secondary cancers among HCT recipients.

  11. Secondary solid cancer screening following hematopoietic cell transplantation

    Science.gov (United States)

    Inamoto, Y; Shah, NN; Savani, BN; Shaw, BE; Abraham, AA; Ahmed, IA; Akpek, G; Atsuta, Y; Baker, KS; Basak, GW; Bitan, M; DeFilipp, Z; Gregory, TK; Greinix, HT; Hamadani, M; Hamilton, BK; Hayashi, RJ; Jacobsohn, DA; Kamble, RT; Kasow, KA; Khera, N; Lazarus, HM; Malone, AK; Lupo-Stanghellini, MT; Margossian, SP; Muffly, LS; Norkin, M; Ramanathan, M; Salooja, N; Schoemans, H; Wingard, JR; Wirk, B; Wood, WA; Yong, A; Duncan, CN; Flowers, MED; Majhail, NS

    2016-01-01

    Hematopoietic stem cell transplant (HCT) recipients have a substantial risk of developing secondary solid cancers, particularly beyond 5 years after HCT and without reaching a plateau overtime. A working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal to facilitate implementation of cancer screening appropriate to HCT recipients. The working group reviewed guidelines and methods for cancer screening applicable to the general population and reviewed the incidence and risk factors for secondary cancers after HCT. A consensus approach was used to establish recommendations for individual secondary cancers. The most common sites include oral cavity, skin, breast and thyroid. Risks of cancers are increased after HCT compared with the general population in skin, thyroid, oral cavity, esophagus, liver, nervous system, bone and connective tissues. Myeloablative TBI, young age at HCT, chronic GVHD and prolonged immunosuppressive treatment beyond 24 months were well-documented risk factors for many types of secondary cancers. All HCT recipients should be advised of the risks of secondary cancers annually and encouraged to undergo recommended screening based on their predisposition. Here we propose guidelines to help clinicians in providing screening and preventive care for secondary cancers among HCT recipients. PMID:25822223

  12. Blood and marrow transplant clinical trials network toxicity committee consensus summary: thrombotic microangiopathy after hematopoietic stem cell transplantation.

    Science.gov (United States)

    Ho, Vincent T; Cutler, Corey; Carter, Shelly; Martin, Paul; Adams, Roberta; Horowitz, Mary; Ferrara, James; Soiffer, Robert; Giralt, Sergio

    2005-08-01

    The syndrome of microangiopathic hemolysis associated with renal failure, neurologic impairment, or both is a recognized complication of hematopoietic stem cell transplantation. This entity is often called hemolytic uremic syndrome (HUS) or thrombotic thrombocytopenic purpura (TTP), yet it is clear that the pathophysiology of transplant-associated HUS/TTP is different from that of classic HUS or TTP. Furthermore, the incidence of this syndrome varies from 0.5% to 76% in different transplant series, primarily because of the lack of a uniform definition. The toxicity committee of the Blood and Marrow Transplant Clinical Trials Network has reviewed the current literature on transplant-related HUS/TTP and recommends that it be henceforth renamed posttransplantation thrombotic microangiopathy (TMA). An operational definition for TMA based on the presence of microangiopathic hemolysis and renal and/or neurologic dysfunction is proposed. The primary intervention after diagnosis of TMA should be withdrawal of calcineurin inhibitors. Plasma exchange, although frequently used in this condition, has not been proven to be effective. In the absence of definitive trials, plasma exchange cannot be considered a standard of care for TMA. It is hoped that these positions will improve the identification and reporting of this devastating complication after hematopoietic stem cell transplantation and facilitate future clinical studies for its prevention and treatment.

  13. Mesenchymal stem cell transplantation ameliorates motor function deterioration of spinocerebellar ataxia by rescuing cerebellar Purkinje cells

    Directory of Open Access Journals (Sweden)

    Ma Wei-Hsien

    2011-08-01

    Full Text Available Abstract Background Spinocerebellar ataxia (SCA refers to a disease entity in which polyglutamine aggregates are over-produced in Purkinje cells (PCs of the cerebellum as well as other neurons in the central nervous system, and the formation of intracellular polyglutamine aggregates result in the loss of neurons as well as deterioration of motor functions. So far there is no effective neuroprotective treatment for this debilitating disease although numerous efforts have been made. Mesenchymal stem cells (MSCs possess multi-lineage differentiation potentials as well as immuno-modulatory properties, and are theoretically good candidates for SCA treatment. The purpose of this study is to investigate whether transplantation of human MSCs (hMSCs can rescue cerebellar PCs and ameliorate motor function deterioration in SCA in a pre-clinical animal model. Method Transgenic mice bearing poly-glutamine mutation in ataxin-2 gene (C57BL/6J SCA2 transgenic mice were serially transplanted with hMSCs intravenously or intracranially before and after the onset of motor function loss. Motor function of mice was evaluated by an accelerating protocol of rotarod test every 8 weeks. Immunohistochemical stain of whole brain sections was adopted to demonstrate the neuroprotective effect of hMSC transplantation on cerebellar PCs and engraftment of hMSCs into mice brain. Results Intravenous transplantation of hMSCs effectively improved rotarod performance of SCA2 transgenic mice and delayed the onset of motor function deterioration; while intracranial transplantation failed to achieve such neuroprotective effect. Immunohistochemistry revealed that intravenous transplantation was more effective in the preservation of the survival of cerebellar PCs and engraftment of hMSCs than intracranial injection, which was compatible to rotarod performance of transplanted mice. Conclusion Intravenous transplantation of hMSCs can indeed delay the onset as well as improve the motor

  14. Allogeneic fetal stem cell transplantation to child with psychomotor retardation: A case report

    OpenAIRE

    2016-01-01

    Introduction. The consequences of autologous and allogeneic stem cell transplantation (stem cells of hematopoiesis), applied in adults and children suffering from leukemia or some other malignant disease, are well-known and sufficiently recognizable in pediatric clinical practice regardless of the indication for the treatment. However, the efficacy of fetal stem cell transplantation is unrecognizable when the indications are psychomotor retardation and epil...

  15. Co-transplantation of macaque autologous Schwann cells and human embryonic nerve stem cells in treatment of macaque Parkinson's disease

    Institute of Scientific and Technical Information of China (English)

    Ying Xia; Chengchuan Jiang; Zuowei Cao; Keshan Shi; Yang Wang

    2012-01-01

    Objective:To investigate the therapeutic effects of co-transplantation with Schwann cells (SCs) and human embryonic nerve stem cells (NSCs) on macaque Parkinson's disease (PD). Methods:Macaque autologous SCs and human embryonic NSCs were adopted for the treatment of macaque PD. Results: Six months after transplantation, positron emission computerized tomography showed that 18F-FP-β-CIT was significantly concentrated in the injured striatum in the co-transplanted group. Immunohistochemical staining of transplanted area tissue showed migration of tyroxine hydroxylase positive cells from the transplant area to the surrounding area was significantly increased in the co-transplanted group. Conclusions: Co-transplantation of SCs and NSCs could effectively cure PD in macaques. SCs harvested from the autologous peripheral nerves can avoid rejection and the ethics problems, so it is expected to be applied clinically.

  16. Donor lymphocyte infusion after allogeneic stem cell transplantation.

    Science.gov (United States)

    Castagna, Luca; Sarina, Barbara; Bramanti, Stefania; Perseghin, Paolo; Mariotti, Jacopo; Morabito, Lucio

    2016-06-01

    Allogeneic stem cell transplantation (allo-SCT) is considered the cornerstone in the treatment of several malignant and not malignant hematological diseases. However, relapse of hematological disease after allo-SCT is considered the most challenging point in the field. The risk can be reduced through optimal patients, donor and disease selection before allo-SCT, but harnessing donor immune system is an appealing way to treat or avoid disease relapse. Donor lymphocyte infusion (DLI) is a simple and effective therapy after allo-SCT. In this paper, the efficacy of DLI will be analyzed in different hematological diseases, focusing also on their therapeutic or pre-emptive use.

  17. Lung function after allogeneic hematopoietic stem cell transplantation in children

    DEFF Research Database (Denmark)

    Uhlving, Hilde Hylland; Larsen Bang, Cæcilie; Christensen, Ib Jarle

    2013-01-01

    Reduction in pulmonary function (PF) has been reported in up to 85% of pediatric patients during the first year after hematopoietic stem cell transplantation (HSCT). Our understanding of the etiology for this decrease in lung function is, however, sparse. The aim of this study was to describe PF...... experienced a decline in lung function of more than 10% during the first 3 to 9 months after HSCT. The decline in forced expiratory volume in 1 second, forced expiratory volume in 1 second/forced vital capacity and diffusion capacity of the lung for carbon monoxide were strongly associated with acute graft...

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    therapeutic option if a suitable HLA-matched stem-cell donation is available. Reduced-intensity conditioning was particularly safe, and mixed-donor chimerism seems sufficient to prevent significant symptoms, although careful long-term monitoring will be required for these patients....... Blood and Marrow Transplant Research. RESULTS: At a median follow-up of 62 months (extending to 14 years), the overall survival rate was 75%. Myeloablative conditioning regimens were used in 28 patients, and reduced-intensity conditioning in 8 patients, with no deaths in this subgroup. Survival rates...

  19. THE PURE RED BLOOD CELL APLASIA IN RENAL TRANSPLANT RECIPIENT

    Directory of Open Access Journals (Sweden)

    B. T. Dzumabaeva

    2011-01-01

    Full Text Available The pure red blood cell aplasia of renal transplant recipients caused by parvovirus B19 (PB19 is characterized by persistent anemia which resistant to erythropoietin therapy, lack of reticulocytes, bone marrow hypoplasia, and clinically accompanied by severe recurrent bacterial, fungal and viral infection. In case of reactivation PB19 it is necessarv, first of all, eliminate the causes activation of this virus and to cancel or reduce the dose of drugs which depressed the normal hematopoiesis germs, thus to reduce the pancytopenia associating complications in this population. 

  20. GVHD (Graft-Versus-Host Disease): A Guide for Patients and Families After Stem Cell Transplant

    Science.gov (United States)

    ... Disease): A guide for patients and families after stem cell transplant The immune system is the body's tool ... and attacking them. When you receive a donor's stem cells (the “graft”), the stem cells recreate the donor's ...

  1. B cells and plasma cells in coronaries of chronically rejected cardiac transplants.

    Science.gov (United States)

    Wehner, Jennifer R; Fox-Talbot, Karen; Halushka, Marc K; Ellis, Carla; Zachary, Andrea A; Baldwin, William M

    2010-05-15

    BACKGROUND.: Previously, we reported that transcripts of immunoglobulins were increased in coronary arteries dissected from cardiac transplants with arteriopathy, but the prevelance and patterns of B cell and plasma cell infiltration in cardiac allografts has not been documented. METHODS.: In this study, we documented the frequency and distribution of B cells and plasma cells in 16 cardiac transplants with advanced chronic rejection that were explanted during a second transplant procedure. Coronary arteries with pathologically confirmed allograft vasculopathy and controls with native atherosclerosis were immunohistologically stained for markers of T cells, B cells, plasma cells, IgG subclasses, C4d, CD21, and CXCL13. RESULTS.: We found that B cells and plasma cells were prevalent in most of the samples analyzed (14 of 16) and were distributed in three patterns: adventitial nodules, diffuse adventitial infiltrates, and neointimal infiltrates. These cells were found most frequently in nodules, some of which had distinct compartmentalization and granular C4d deposits on follicular dendritic cells (FDCs) that typify tertiary lymphoid nodules. FDCs also stained for CD21 and CXCL13. Diffuse infiltrates of B cells and plasma cells were found in fibrotic areas of the neointima and adventitia. Only a minority of control coronaries with atherosclerosis contained B cells. CONCLUSIONS.: B cells and plasma cell infiltrates are consistent findings in and around coronary arteries with allograft vasculopathy and are significantly more frequent than in coronaries with native atherosclerosis. The presence of C4d on FDCs in tertiary lymphoid nodules suggests active antigen presentation.

  2. Human Satellite Cell Transplantation and Regeneration from Diverse Skeletal Muscles

    Directory of Open Access Journals (Sweden)

    Xiaoti Xu

    2015-09-01

    Full Text Available Identification of human satellite cells that fulfill muscle stem cell criteria is an unmet need in regenerative medicine. This hurdle limits understanding how closely muscle stem cell properties are conserved among mice and humans and hampers translational efforts in muscle regeneration. Here, we report that PAX7 satellite cells exist at a consistent frequency of 2–4 cells/mm of fiber in muscles of the human trunk, limbs, and head. Xenotransplantation into mice of 50–70 fiber-associated, or 1,000–5,000 FACS-enriched CD56+/CD29+ human satellite cells led to stable engraftment and formation of human-derived myofibers. Human cells with characteristic PAX7, CD56, and CD29 expression patterns populated the satellite cell niche beneath the basal lamina on the periphery of regenerated fibers. After additional injury, transplanted satellite cells robustly regenerated to form hundreds of human-derived fibers. Together, these findings conclusively delineate a source of bona-fide endogenous human muscle stem cells that will aid development of clinical applications.

  3. Status Epilepticus Due to Severe HHV-6 Encephalitis in an Allogeneic Stem Cell Transplant Recipient

    Directory of Open Access Journals (Sweden)

    Poorvi Chordia

    2013-12-01

    Full Text Available Reactivation of human herpes virus-6 (HHV-6 after stem cell transplantation occurs frequently. It is associated with clinical manifestations varying from nonspecific symptoms such as fevers or rash, to severe life threatening complications including post-transplantation limbic encephalitis. We report a case of severe HHV-6 encephalitis with viremia in an allogeneic peripheral stem cell transplant recipient who presented with status epilepticus unresponsive to antiepileptic therapy.  With intravenous ganciclovir and supportive care, the patient’s condition improved. Awareness of HHV-6 infection in stem cell transplant recipients may help with early diagnosis and improved outcome.

  4. Endovascular Method for Transplantation of Insulin-Producing Cells to the Pancreas Parenchyma in Swine

    OpenAIRE

    Lundberg, J.; Stone-Elander, S.; Zhang, X. -M; Korsgren, Olle; Jonsson, S; Holmin, S.

    2014-01-01

    Insulin-producing cells are transplanted by portal vein injection as an alternative to pancreas transplantation in both clinical and preclinical trials. Two of the main limitations of portal vein transplantation are the prompt activation of the innate immunity and concomitant loss of islets and a small but significant risk of portal vein thrombosis. Furthermore, to mimic physiological release, the insulin-producing cells should instead be located in the pancreas. The trans-vessel wall approac...

  5. Delayed massive immune hemolysis mediated by minor ABO incompatibility after allogeneic peripheral blood progenitor cell transplantation.

    OpenAIRE

    Salmon, Jean; Michaux, S.; Hermanne, J. P.; Baudoux, Etienne; Gerard, Christiane; Sondag, Danièle; Fillet, Georges; Beguin, Yves

    1999-01-01

    BACKGROUND: Bone marrow transplantation with minor ABO incompatibility may be followed by moderate delayed hemolysis of the recipient's red cells by donor-derived ABO antibodies. This reaction may be more severe after transplantation of peripheral blood progenitor cells (PBPCs). CASE REPORT: A 16-year-old boy underwent an allogeneic PBPC transplant from his HLA-mismatched mother as treatment for acute myeloblastic leukemia that had proved resistant to induction chemotherapy. Transfusion of th...

  6. High-grade cytomegalovirus antigenemia after hematopoietic stem cell transplantation.

    Science.gov (United States)

    Asano-Mori, Y; Oshima, K; Sakata-Yanagimoto, M; Nakagawa, M; Kandabashi, K; Izutsu, K; Hangaishi, A; Motokura, T; Chiba, S; Kurokawa, M; Hirai, H; Kanda, Y

    2005-11-01

    Clinical impact of high-grade (HG) cytomegalovirus (CMV) antigenemia after hematopoietic stem cell transplantation has not been clarified. Therefore, in order to investigate the risk factors and outcome for HG-CMV antigenemia, we retrospectively analyzed the records of 154 Japanese adult patients who underwent allogeneic hematopoietic stem cell transplantation for the first time from 1995 to 2002 at the University of Tokyo Hospital. Among 107 patients who developed positive CMV antigenemia at any level, 74 received risk-adapted preemptive therapy with ganciclovir (GCV), and 17 of these developed HG-antigenemia defined as > or = 50 positive cells per two slides. The use of systemic corticosteroids at > or = 0.5 mg/kg/day at the initiation of GCV was identified as an independent significant risk factor for HG-antigenemia. Seven of the 17 HG-antigenemia patients developed CMV disease, with a cumulative incidence of 49.5%, which was significantly higher than that in the low-grade antigenemia patients (4%, P<0.001). However, overall survival was almost equivalent in the two groups. In conclusion, the development of HG-antigenemia appeared to depend on the profound immune suppression of the recipient. Although CMV disease frequently developed in HG-antigenemia patients, antiviral therapy could prevent a fatal outcome.

  7. Therapeutic Potential of Autologous Stem Cell Transplantation for Cerebral Palsy

    Directory of Open Access Journals (Sweden)

    Chaitanya Purandare

    2012-01-01

    Full Text Available Background. Cerebral palsy (CP is a severe disabling disease with worldwide incidence being 2 to 3 per 1000 live births. CP was considered as a noncurable, nonreparative disorder, but stem cell therapy offers a potential treatment for CP. Objective. The present study evaluates the safety and efficacy of autologous bone-marrow-derived mononuclear cell (BMMNCs transplantation in CP patient. Material and Methods. In the present study, five infusions of autologous stem cells were injected intrathecally. Changes in neurological deficits and improvements in function were assessed using Gross Motor Function Classification System (GMFCS-E&R scale. Results. Significant motor, sensory, cognitive, and speech improvements were observed. Bowel and bladder control has been achieved. On the GMFCS-E&R level, the patient was promoted from grade III to I. Conclusion. In this study, we report that intrathecal infusion of autologous BMMNCs seems to be feasible, effective, and safe with encouraging functional outcome improvements in CP patient.

  8. Stem cell derived interneuron transplants as a treatment for schizophrenia: preclinical validation in a rodent model

    Science.gov (United States)

    Donegan, Jennifer J.; Tyson, Jennifer A.; Branch, Sarah Y.; Beckstead, Michael J.; Anderson, Stewart A.; Lodge, Daniel J.

    2016-01-01

    An increasing literature suggests that schizophrenia is associated with a reduction in hippocampal interneuron function. Thus, we posit that stem cell-derived interneuron transplants may be an effective therapeutic strategy to reduce hippocampal hyperactivity and attenuate behavioral deficits in schizophrenia. Here we used a dual-reporter embryonic stem cell line to generate enriched populations of parvalbumin (PV)- or somatostatin (SST)-positive interneurons, which were transplanted into the ventral hippocampus of the methylazoxymethanol (MAM) rodent model of schizophrenia. These interneuron transplants integrate within the existing circuitry, reduce hippocampal hyperactivity, and normalize aberrant dopamine neuron activity. Further, interneuron transplants alleviate behaviors that model negative and cognitive symptoms, including deficits in social interaction and cognitive inflexibility. Interestingly, PV- and SST-enriched transplants produced differential effects on behavior, with PV-enriched populations effectively normalizing all the behaviors examined. These data suggest that stem cell-derived interneuron transplants may represent a novel therapeutic strategy for schizophrenia. PMID:27480492

  9. Neurons Differentiated from Transplanted Stem Cells Respond Functionally to Acoustic Stimuli in the Awake Monkey Brain.

    Science.gov (United States)

    Wei, Jing-Kuan; Wang, Wen-Chao; Zhai, Rong-Wei; Zhang, Yu-Hua; Yang, Shang-Chuan; Rizak, Joshua; Li, Ling; Xu, Li-Qi; Liu, Li; Pan, Ming-Ke; Hu, Ying-Zhou; Ghanemi, Abdelaziz; Wu, Jing; Yang, Li-Chuan; Li, Hao; Lv, Long-Bao; Li, Jia-Li; Yao, Yong-Gang; Xu, Lin; Feng, Xiao-Li; Yin, Yong; Qin, Dong-Dong; Hu, Xin-Tian; Wang, Zheng-Bo

    2016-07-26

    Here, we examine whether neurons differentiated from transplanted stem cells can integrate into the host neural network and function in awake animals, a goal of transplanted stem cell therapy in the brain. We have developed a technique in which a small "hole" is created in the inferior colliculus (IC) of rhesus monkeys, then stem cells are transplanted in situ to allow for investigation of their integration into the auditory neural network. We found that some transplanted cells differentiated into mature neurons and formed synaptic input/output connections with the host neurons. In addition, c-Fos expression increased significantly in the cells after acoustic stimulation, and multichannel recordings indicated IC specific tuning activities in response to auditory stimulation. These results suggest that the transplanted cells have the potential to functionally integrate into the host neural network.

  10. Effect of endothelial progenitor cell on hematopoietic reconstitution in allogeneic hematopoietic stem cell transplantation mouse model

    Institute of Scientific and Technical Information of China (English)

    化静

    2013-01-01

    Objective To examine the effects of endothelial progenitor cell (EPC) on hematopoietic reconsititution in allogeneic hematopoietic stem cell transplantation (alloHSCT) mouse model.Methods Allo-HSCT mouse model was established with condition of BU/CY,in which C57BL/6 (H-2b) and BABL/c (H-2d) mice were used

  11. Fetal liver cell transplantation : role and nature of the fetal haemopoietic stem cell

    NARCIS (Netherlands)

    B. Löwenberg (Bob)

    1975-01-01

    textabstractFetal liver cell transplantation deserves intensified interest because, according to previous experimental evidence, it may represent a useful approach to reduce or avoid severe Graft-versus-Host (GvH) reactions following treatment with allogeneic haemopoietic cell grafts. The applicatio

  12. Up-front autologous stem-cell transplantation in peripheral T-cell lymphoma

    DEFF Research Database (Denmark)

    d'Amore, Francesco; Relander, Thomas; Lauritzsen, Grete F;

    2012-01-01

    Systemic peripheral T-cell lymphomas (PTCLs) respond poorly to conventional therapy. To evaluate the efficacy of a dose-dense approach consolidated by up-front high-dose chemotherapy (HDT) and autologous stem-cell transplantation (ASCT) in PTCL, the Nordic Lymphoma Group (NLG) conducted a large p...

  13. Transplantation of neural progenitor cells differentiated from adipose tissue-derived stem cells for treatment of sciatic nerve injury

    Institute of Scientific and Technical Information of China (English)

    Shasha Dong§; Na Liu§; Yang Hu ; Ping Zhang; Chao Pan; Youping Zhang; Yingxin Tang; Zhouping Tang 

    2016-01-01

    Objectives: Currently, the clinical repair of sciatic nerve injury remains difficult. Previous studies have confirmed that transplantation of adipose tissue-derived stem cells promotes nerve regeneration and restoration at peripheral nerve injury sites. Methods:In this study, adipose tissue-derived stem cells were induced to differentiate into neural progenitor cells, transfected with a green fluorescent protein-containing lentivirus, and then transplanted into the lesions of rats with sciatic nerve compression injury. Results: Fluorescence microscopy revealed that the transplanted cells survived, migrated, and differentiated in rats. At two weeks post-operation, a large number of transplanted cells had migrated to the injured lesions; at six weeks post-operation, transplanted cells were visible around the injured nerve and several cells were observed to express a Schwann cell marker. Sciatic function index and electrophysiological outcomes of the transplantation group were better than those of the control group. Cell transplantation promoted the recovery of motor nerve conduction velocity and com-pound muscle action potential amplitude, and reduced gastrocnemius muscle atrophy. Conclusions: Our experimental findings indicate that neural progenitor cells, differentiated from adipose tissue-derived stem cells, are potential seed stem cells that can be transplanted into lesions to treat sciatic nerve injury. This provides a theoretical basis for their use in clinical applications.

  14. Fecal microbiota transplantation for recurrent Clostridium difficile infection in hematopoietic stem cell transplant recipients.

    Science.gov (United States)

    Webb, B J; Brunner, A; Ford, C D; Gazdik, M A; Petersen, F B; Hoda, D

    2016-08-01

    Recurrent Clostridium difficile infection (CDI) is a consequence of intestinal dysbiosis and is particularly common following hematopoietic stem cell transplantation (HSCT). Fecal microbiota transplantation (FMT) is an effective method of treating CDI by correcting intestinal dysbiosis by passive transfer of healthy donor microflora. FMT has not been widely used in immunocompromised patients, including HSCT recipients, owing to concern for donor-derived infection. Here, we describe initial results of an FMT program for CDI at a US HSCT center. Seven HSCT recipients underwent FMT between February 2015 and February 2016. Mean time post HSCT was 635 days (25-75 interquartile range [IQR] 38-791). Five of the patients (71.4%) were on immunosuppressive therapy at FMT; 4 had required long-term suppressive oral vancomycin therapy because of immediate recurrence after antibiotic cessation. Stool donors underwent comprehensive health and behavioral screening and laboratory testing of serum and stool for 32 potential pathogens. FMT was administered via the naso-jejunal route in 6 of the 7 patients. Mean follow-up was 265 days (IQR 51-288). Minor post-FMT adverse effects included self-limited bloating and urgency. One patient was suspected of having post-FMT small intestinal bacterial overgrowth. No serious adverse events were noted and all-cause mortality was 0%. Six of 7 (85.7%) patients had no recurrence; 1 patient recurred at day 156 post FMT after taking an oral antibiotic and required repeat FMT, after which no recurrence has occurred. Diarrhea was improved in all patients and 1 patient with gastrointestinal graft-versus-host disease was able to taper off systemic immunosuppression after FMT. With careful donor selection and laboratory screening, FMT appears to be a safe and effective therapy for CDI in HSCT patients and may confer additional benefits. Larger studies are necessary to confirm safety and efficacy and explore other possible effects.

  15. Transplantation of mouse fetal liver cells for analyzing the function of hematopoietic stem and progenitor cells.

    Science.gov (United States)

    Gudmundsson, Kristbjorn Orri; Stull, Steven W; Keller, Jonathan R

    2012-01-01

    Hematopoietic stem cells are defined by their ability to self-renew and differentiate through progenitor cell stages into all types of mature blood cells. Gene-targeting studies in mice have demonstrated that many genes are essential for the generation and function of hematopoietic stem and progenitor cells. For definitively analyzing the function of these cells, transplantation studies have to be performed. In this chapter, we describe methods to isolate and transplant fetal liver cells as well as how to analyze donor cell reconstitution. This protocol is tailored toward mouse models where embryonic lethality precludes analysis of adult hematopoiesis or where it is suspected that the function of fetal liver hematopoietic stem and progenitor cells is compromised.

  16. Regulating regulator y T cells to achieve transplant tolerance

    Institute of Scientific and Technical Information of China (English)

    Ran Tao; Wayne W. Hancock

    2007-01-01

    BACKGROUND:Regulatory T cells (Tregs) play crucial roles in both induction and maintenance of tolerance. This active immune regulation may contribute not only to the control of immune responses to self-antigens and thereby prevent autoimmune diseases, but also the control of responses to non-self molecules in adaptive immunity. Numerous experimental and clinical studies indicate that manipulating the balance between regulatory and responder T cells is an effective strategy to control immune responsiveness after transplantation. DATA SOURCES:Literature search was conducted using PubMed on the related subjects. Part of the material was based on the most recent work in the authors' laboratory. RESULTS: We propose some new strategies to achieve transplant tolerance in rodent animals via manipulating Treg function, including using histone deacetylase (HDAC) inhibitor to regulate Foxp3 transcription and enhance Treg suppression, induction of Treg-sparing apoptosis via Nur77, and identiifcation of the co-inhibitory molecule herpes virus entry mediator (HVEM) as an effector molecule for Treg function. CONCLUSION:Regulation of Treg function will deifnitely provide us very promising tools to achieve clinical tolerance in the future.

  17. THROMBOTIC MICROANGIOPATHY IN HAEMATOPOIETIC CELL TRANSPLANTATION:AN UPDATE

    Directory of Open Access Journals (Sweden)

    Evi Stavrou

    2010-10-01

    Full Text Available Allogeneic hematopoietic cell transplantation (HCT represents a vital procedure for patients with various hematologic conditions. Despite advances in the field, HCT carries significant morbidity and mortality. A rare but potentially devastating complication is transplantation-associated thrombotic microangiopathy (TA-TMA. In contrast to idiopathic TTP, whose etiology is attributed to deficient activity of ADAMTS13, (a member of the A Disintegrin And Metalloprotease with Thrombospondin 1 repeats family of metalloproteases, patients with TA-TMA have > 5% ADAMTS13 activity. Pathophysiologic mechanisms associated with TA-TMA, include loss of endothelial cell integrity induced by intensive conditioning regimens, immunosuppressive therapy, irradiation, infections and graft-versus-host (GVHD disease. The reported incidence of TA-TMA ranges from 0.5% to 75%, reflecting the difficulty of accurate diagnosis in these patients. Two different groups have proposed consensus definitions for TA-TMA, yet they fail to distinguish the primary syndrome from secondary causes such as infections or medication exposure. Despite treatment, mortality rate in TA-TMA ranges between 60% to 90%. The treatment strategies for TA-TMA remain challenging. Calcineurin inhibitors should be discontinued and replaced with alternative immunosuppressive agents.  Daclizumab, a humanized monoclonal anti-CD25 antibody, has shown promising results in the treatment of TA-TMA. Rituximab or the addition of defibrotide, have been reported to induce remission in this patient population. In general, plasma exchange is not recommended.

  18. Rhesus monkey neural stem cell transplantation promotes neural regeneration in rats with hippocampal lesions.

    Science.gov (United States)

    Ye, Li-Juan; Bian, Hui; Fan, Yao-Dong; Wang, Zheng-Bo; Yu, Hua-Lin; Ma, Yuan-Ye; Chen, Feng

    2016-09-01

    Rhesus monkey neural stem cells are capable of differentiating into neurons and glial cells. Therefore, neural stem cell transplantation can be used to promote functional recovery of the nervous system. Rhesus monkey neural stem cells (1 × 10(5) cells/μL) were injected into bilateral hippocampi of rats with hippocampal lesions. Confocal laser scanning microscopy demonstrated that green fluorescent protein-labeled transplanted cells survived and grew well. Transplanted cells were detected at the lesion site, but also in the nerve fiber-rich region of the cerebral cortex and corpus callosum. Some transplanted cells differentiated into neurons and glial cells clustering along the ventricular wall, and integrated into the recipient brain. Behavioral tests revealed that spatial learning and memory ability improved, indicating that rhesus monkey neural stem cells noticeably improve spatial learning and memory abilities in rats with hippocampal lesions.

  19. Restoration of spermatogenesis after transplantation of c-Kit positive testicular cells in the fowl

    Science.gov (United States)

    Transplantation of male germ line cells into sterilized recipients has been used in mammals for conventional breeding as well as for transgenesis. This study presents an improvement in the approach for germ cell transplantation between fowl males by using an enriched subpopulation of c-Kit positive ...

  20. 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

    2003-01-01

    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 s

  1. The outcome of thirteen patients with nonmalignant hematologic diseases treated with HLA haploidentical stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    陶媛

    2014-01-01

    Objective To evaluate the clinical efficacy and safety of human leukocyte antigen(HLA)haploidentical stem cell transplantation in nonmalignant hematologic diseases.Methods To analyze the outcome of 13 patients with nonmalignant hematologic diseases who underwent HLA haploidentical stem cell transplantation from September

  2. Persistent seropositivity for yellow fever in a previously vaccinated autologous hematopoietic stem cell transplantation recipient.

    Science.gov (United States)

    Hayakawa, Kayoko; Takasaki, Tomohiko; Tsunemine, Hiroko; Kanagawa, Shuzo; Kutsuna, Satoshi; Takeshita, Nozomi; Mawatari, Momoko; Fujiya, Yoshihiro; Yamamoto, Kei; Ohmagari, Norio; Kato, Yasuyuki

    2015-08-01

    The duration of a protective level of yellow fever antibodies after autologous hematopoietic stem cell transplantation in a previously vaccinated person is unclear. The case of a patient who had previously been vaccinated for yellow fever and who remained seropositive for 22 months after autologous peripheral blood stem cell transplantation for malignant lymphoma is described herein.

  3. ATP-ase positive cells in human oral mucosa transplanted to nude mice

    DEFF Research Database (Denmark)

    Dabelsteen, E; Kirkeby, S

    1981-01-01

    A model to study the differentiation of human oral epithelium in vivo utilizing transplantation of human tissue to nude mice has been described. Previous studies have described the epithelial cells in this model. In this study we demonstrate that 8 d after transplantation, Langerhans cells, ident...

  4. Allogeneic hematopoietic stem cell transplantation in patients with diffuse large B cell lymphoma relapsed after autologous stem cell transplantation: a GITMO study.

    Science.gov (United States)

    Rigacci, Luigi; Puccini, Bendetta; Dodero, Anna; Iacopino, Pasquale; Castagna, Luca; Bramanti, Stefania; Ciceri, Fabio; Fanin, Renato; Rambaldi, Alessandro; Falda, Michele; Milone, Giuseppe; Guidi, Stefano; Martelli, Massimo Fabrizio; Mazza, Patrizio; Oneto, Rosi; Bosi, Alberto

    2012-06-01

    Patients who relapse after an autologous hematopoietic stem cell transplantation (SCT) have a very poor prognosis. We have retrospectively analyzed diffuse large B cell lymphoma patients who underwent an allo-SCT after an auto-SCT relapse reported in the Gruppo Italiano Trapianto di Midollo Osseo (GITMO) database. From 1995 to 2008, 3449 autologous transplants were reported in the GITMO database. Eight hundred eighty-four patients relapsed or progressed after transplant; 165 patients, 19% of the relapsed patients, were treated with allo-transplant. The stem cell donor was related to the patient in 108 cases. A reduced intensity conditioning regimen was used in 116. After allo-SCT, 72 patients (43%) obtained a complete response and 9 obtained a partial response with an overall response rate of 49%; 84 patients (51%) experienced rapid progression of disease. Ninety-one patients died, 45 due to disease and 46 due to treatment-related mortality. Acute graft-versus-host disease was recorded in 57 patients and a chronic GvHD in 38 patients. With a median follow-up of 24 months (2-144) after allo, overall survival (OS) was 39%, and after a median of 21 months (2-138) after allo, progression-free survival (PFS) was 32%. Multivariate analysis indicated that the only factors affecting OS were status at allo-SCT, and those affecting PFS were status at allo-SCT and stem cell donor. This retrospective analysis shows that about one-fifth of patients with diffuse large B cell lymphoma who experience relapse after autologous transplantation may be treated with allogeneic transplantation. Moreover, the only parameter affecting either OS or PFS was the response status at the time of allo-SCT.

  5. Optimal time for human umbilical cord blood cell transplantation in rats with myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    XING Yun-li; SHEN Lu-hua; LI Hong-wei; ZHANG Yu-chen; ZHAO Lin; ZHAO Shu-mei; XU Qing

    2009-01-01

    Background Cell therapy for cardiac regeneration is still under investigation. To date there have been a limited number of studies describing the optimal time for cell injection. The present study aimed to examine the optimal time for human umbilical cord blood cells (HUCBCs) transplantation after myocardial infarction (MI).Methods The animals underwent MI by ligation of the left anterior descending coronary artery and received an intravenous injection of equal volumes of HUCBCs or phosphate buffered saline at days 1,5,10 and 30 after MI. HUCBCs were detected by immunostaining against human human leucocyte antigen (HLA). Cardiac function, histological analysis and measurement of vascular endothelial growth factor (VEGF) were performed 4 weeks after cell transplantation. Results HUCBCs transplantation could improve cardiac function in rats that received transplantation at 5 and 10 days after MI. The best benefit was achieved in rats that received cells at 10-day after MI. Survival of engrafted HUCBCs, angiogenesis and VEGF expression were more obvious in the 10-day transplantation group than in the other transplantation groups. No evidence of cardiomyocyte regeneration was detected in any transplanted rats. Conclusions HUCBCs transplantation could improve cardiac function in rats that received HUCBCs at days 5 and 10 after MI with the optimal time for transplantation being 10 days post MI. Angiogenesis, but not cardiomyocyte regeneration, played a key role in the cardiac function improvement.

  6. Cell transplantation for the treatment of spinal cord injury- bone marrow stromal cells and choroid plexus epithelial cells

    Institute of Scientific and Technical Information of China (English)

    Chizuka Ide; Norihiko Nakano; Kenji Kanekiyo

    2016-01-01

    Transplantation of bone marrow stromal cells (BMSCs) enhanced the outgrowth of regenerating axons and promoted locomotor improvements of rats with spinal cord injury (SCI). BMSCs did not survive long-term, disappearing from the spinal cord within 2–3 weeks after transplantation. Astrocyte-devoid areas, in which no astrocytes or oligodendrocytes were found, formed at the epicenter of the lesion. It was remarkable that numerous regenerating axons extended through such astrocyte-devoid areas. Regenerating axons were associated with Schwann cells embedded in extracellular matrices. Transplantation of choroid plexus epithelial cells (CPECs) also enhanced axonal regeneration and locomotor improvements in rats with SCI. Although CPECs disappeared from the spinal cord shortly after transplantation, an extensive outgrowth of regenerating axons occurred through astrocyte-devoid areas, as in the case of BMSC transplantation. These ifndings suggest that BMSCs and CPECs secret neurotrophic factors that promote tissue repair of the spinal cord, including axonal regeneration and reduced cavity formation. This means that transplantation of BMSCs and CPECs promotes “intrinsic” ability of the spinal cord to regenerate. The treatment to stimu-late the intrinsic regeneration ability of the spinal cord is the safest method of clinical application for SCI. It should be emphasized that the generally anticipated long-term survival, proliferation and differentiation of transplanted cells are not necessarily desirable from the clinical point of view of safety.

  7. Could Cells from Your Nose Fix Your Heart? Transplantation of Olfactory Stem Cells in a Rat Model of Cardiac Infarction

    Directory of Open Access Journals (Sweden)

    Cameron McDonald

    2010-01-01

    Full Text Available This study examines the hypothesis that multipotent olfactory mucosal stem cells could provide a basis for the development of autologous cell transplant therapy for the treatment of heart attack. In humans, these cells are easily obtained by simple biopsy. Neural stem cells from the olfactory mucosa are multipotent, with the capacity to differentiate into developmental fates other than neurons and glia, with evidence of cardiomyocyte differentiation in vitro and after transplantation into the chick embryo. Olfactory stem cells were grown from rat olfactory mucosa. These cells are propagated as neurosphere cultures, similar to other neural stem cells. Olfactory neurospheres were grown in vitro, dissociated into single cell suspensions, and transplanted into the infarcted hearts of congeneic rats. Transplanted cells were genetically engineered to express green fluorescent protein (GFP in order to allow them to be identified after transplantation. Functional assessment was attempted using echocardiography in three groups of rats: control, unoperated; infarct only; infarcted and transplanted. Transplantation of neurosphere-derived cells from adult rat olfactory mucosa appeared to restore heart rate with other trends towards improvement in other measures of ventricular function indicated. Importantly, donor-derived cells engrafted in the transplanted cardiac ventricle and expressed cardiac contractile proteins.

  8. Bone Marrow-Derived Stem Cell Transplantation for the Treatment of Insulin-Dependent Diabetes

    OpenAIRE

    2010-01-01

    The bone marrow is an invaluable source of adult pluripotent stem cells, as it gives rise to hematopoietic stem cells, endothelial progenitor cells, and mesenchymal cells, amongst others. The use of bone marrow-derived stem cell (BMC) transplantation (BMT) may be of assistance in achieving tissue repair and regeneration, as well as in modulating immune responses in the context of autoimmunity and transplantation. Ongoing clinical trials are evaluating the effects of BMC to preserve functiona...

  9. New approaches to manipulate minimal residual disease after allogeneic stem cell transplantation.

    Science.gov (United States)

    Rein, Lindsay Am; Sung, Anthony D; Rizzieri, David A

    2013-02-01

    Minimal residual disease (MRD) is a complex topic that has been studied extensively in hematologic malignancies given its clinical implications related to prognosis. However, methods to monitor and treat MRD, especially after stem cell transplantation, are not well defined and vary in different disease processes. Alternative transplant strategies, such as reduced-intensity conditioning, have altered the way we assess and address MRD after transplantation. Development of new diagnostic tools have allowed for higher sensitivity and specificity of testing. Both targeted chemotherapeutic agents and immunotherapies have been developed to treat MRD in hopes of improving patient outcomes. This article aims to address ways to define and manipulate MRD specifically after stem cell transplantation.

  10. Kidney Transplant in a 26-Year-Old Nigerian Patient with Sickle Cell Nephropathy

    Directory of Open Access Journals (Sweden)

    U. H. Okafor

    2012-01-01

    Full Text Available Sickle cell nephropathy (SCN is a common complication of sickle cell disease (SCD. It has variable presentation, ranging from hyposthenuria to end-stage renal disease (ESRD. Management of ESRD in SCD patients is froth with multiple challenges which has potential to impact negatively the outcome of the patient. Kidney transplant is the preferred renal replacement therapy in these patients. The objective of this case study is to report kidney transplant in a Nigerian young man with sickle cell nephropathy and to highlight the outcome and the challenges to kidney transplant in this patient. The index case is a 26-years-old sickle cell disease patient with ESRD complicated with cardiovascular, pulmonary, immunological, and infective challenges. These conditions were controlled, and the patient had a successful live-related kidney transplant. Kidney transplant is a viable option for sickle cell disease patients with ESRD.

  11. Allogeneic hematopoietic cell transplantation without fluconazole and fluoroquinolone prophylaxis.

    Science.gov (United States)

    Heidenreich, D; Kreil, S; Nolte, F; Reinwald, M; Hofmann, W-K; Klein, S A

    2016-01-01

    Fluoroquinolone (FQ) and fluconazole prophylaxis is recommended for patients undergoing allogeneic hematopoietic cell transplantation (alloHCT). However, due to an uncertain scientific basis and the increasing emergence of resistant germs, this policy should be questioned. Therefore, FQ and fluconazole prophylaxis was omitted in alloHCT at our center. In this retrospective analysis, all consecutive patients (n = 63) who underwent first alloHCT at our institution from September 2010 to September 2013 were included. Patients neither received FQ nor fluconazole prophylaxis. Day 100 mortality, incidence of febrile neutropenia, bacterial infections, and invasive fungal diseases (IFD) were assessed. Sixteen patients who started conditioning under antimicrobial treatment/prophylaxis due to pre-existing neutropenia (3/16), IFD (12/16), or aortic valve replacement (1/16) were excluded from the analysis. Finally, 47 patients were transplanted without prophylaxis as intended. Day 100 mortality was 9 %. Febrile neutropenia occurred in 62 % (29/47); 17/47 patients (36 %) experienced a blood stream infection (BSI) with detection of Gram-positive bacteria in 14 patients, Gram-negative bacteria in five patients, and candida in one patient, respectively. Coagulase-negative staphylococci were the most frequently isolated Gram-positive bacteria; 12/21 isolated Gram-positive and 3/6 Gram-negative bacteria were FQ resistant. In 21 % (10/47) of the patients, IFD (1x proven, 1x probable, and 8x possible) were diagnosed. To conclude, all three criteria, day 100 mortality, the incidence of IFD, and BSI, are in the range of published data for patients transplanted with FQ and fluconazole prophylaxis. These data demonstrate that alloHCT is feasible without FQ and fluconazole prophylaxis.

  12. Germ cell transplantation: a potential treatment of severe testicular failure.

    Science.gov (United States)

    Cozzolino, D J; Lamb, D J

    2000-12-01

    Although the process of spermatogenesis is relatively efficient and resistant to damage, male infertility can result from exposure to toxic agents such as chemotherapeutic regimes, radiation, or occupational exposures to chemicals. Other types of infertility may result from migratory defects or poor survival of primordial germ cells during development, abnormal repopulation of the tubules by spermatogonia during development, or low cellularity of the testis (hypospermatogenesis). Presently, there are no effective therapies available to treat these patients. Recent studies in animal models have demonstrated that isolated testicular germ cells collected from testes may be transplanted into sterile recipient mice to regenerate spermatogenesis. This technology will have widespread applications in efforts to manipulate the genome and produce transgenic offspring, to improve agricultural species, to enhance sperm production in endangered species, to improve our understanding of the control mechanisms regulating spermatogenesis, and to treat male infertility.

  13. Hematopoietic stem cell transplantation for severe combined immunodeficiency.

    Science.gov (United States)

    Hönig, M; Schulz, A; Friedrich, W

    2011-11-01

    Severe combined immunodeficiency (SCID) is a heterogeneous group of congenital diseases characterized by their presentation with life threatening infections in the first months of life. The clinical presentation and the therapeutic outcome is influenced by multiple factors: the genetic defect, infectious complications, the presence of maternal T cells the development of Omenn syndrome, as well as non-immunological signs and symptoms of the disease. Hematopoietic stem cell transplantation (HSCT) to date is the only established curative option and allows long-term cure of the disease. Therapeutic objectives of HSCT in SCID clearly differ from those in malignant or hematological disease. Disease specific aspects and their influence on the therapeutic strategy in SCID will be discussed in this review.

  14. Vascular progenitor cells in the development of transplant arteriopathy

    NARCIS (Netherlands)

    Hillebrands, JL; Rienstra, H; Onuta, G; Rozing, J

    2005-01-01

    Although advances in graft procurement, preservation, matching and immunosuppression have all contributed to today's outstanding short-term graft survival rates after solid organ transplantation, similar success has not been achieved in preventing chronic transplant dysfunction (CTD) and extending l

  15. Comparison Between Transepicardial Cell Transplantations: Autologous Undifferentiated Versus Differentiated Marrow Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Farid Azmoudeh Ardalan

    2007-06-01

    Full Text Available Background: Marrow-derived mesenchymal stem cells (MSCs have been heralded as a source of great promise for the regeneration of the infarcted heart. There are no clear data as to whether or not in vitro differentiation of MSCs into major myocardial cells can increase the beneficial effects of MSCs. The aim of this study was to address this issue.Methods: To induce MSCs to transdifferentiate into cardiomyocytes and endothelial cells, 5-Azacytidine and vascular endothelial growth factor (VEGF were used, respectively. Myocardial infarction in rabbits was generated by ligating the left anterior descending coronary artery. The animals were divided into three experimental groups: I control group, II undifferentiated mesenchymal stem cell transplantation group, and III differentiated mesenchymal stem cell transplantation group. The three groups received peri-infarct injections of culture media, autologous undifferentiated MSCs, and autologous differentiated MSCs, respectively. Echocardiography and pathology were performed in order to search for improvement in the cardiac function and reduction in the infarct size. Results: Improvements in the left ventricular function and reductions in the infarcted area were observed in both cell transplanted groups (Groups II and III to the same degree. Conclusions: There is no need for prior differentiation induction of marrow-derived MSCs before transplantation, and peri-infarct implantation of MSCs can effectively reduce the size of the infarct and improve the cardiac function.

  16. NK cells and other innate lymphoid cells in haematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Paola eVacca

    2016-05-01

    Full Text Available Natural Killer (NK cells play a major role in the T-cell depleted haploidentical haematopoietic stem cell transplantation (haplo-HSCT to cure high-risk leukemias. NK cells belong to the expanding family of innate lymphoid cells (ILC. At variance with NK cells, the other ILC populations (ILC1/2/3 are non-cytolytic, while they secrete different patterns of cytokines. ILC provide host defences against viruses, bacteria and parasites, drive lymphoid organogenesis, and contribute to tissue remodelling. In haplo-HSCT patients, the extensive T-cell depletion is required to prevent graft-versus-host disease (GvHD but increases risks of developing a wide range of life-threatening infections. However, these patients may rely on innate defences that are reconstituted more rapidly than the adaptive ones. In this context, ILC may represent important players in the early phases following transplantation. They may contribute to tissue homeostasis/remodelling and lymphoid tissue reconstitution. While the reconstitution of NK cell repertoire and its role in haplo-HSCT have been largely investigated, little information is available on ILC. Of note, CD34+ cells isolated from different sources of HSC, may differentiate in vitro towards various ILC subsets. Moreover, cytokines released from leukemia blasts (e.g. IL-1β may alter the proportions of NK cells and ILC3, suggesting the possibility that leukemia may skew the ILC repertoire. Further studies are required to define the timing of ILC development and their potential protective role after HSCT.

  17. The Power and the Promise of Cell Reprogramming: Personalized Autologous Body Organ and Cell Transplantation

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    Ana Belen Alvarez Palomo

    2014-04-01

    Full Text Available Reprogramming somatic cells to induced pluripotent stem cells (iPSCs or direct reprogramming to desired cell types are powerful and new in vitro methods for the study of human disease, cell replacement therapy, and drug development. Both methods to reprogram cells are unconstrained by the ethical and social questions raised by embryonic stem cells. iPSC technology promises to enable personalized autologous cell therapy and has the potential to revolutionize cell replacement therapy and regenerative medicine. Potential applications of iPSC technology are rapidly increasing in ambition from discrete cell replacement applications to the iPSC assisted bioengineering of body organs for personalized autologous body organ transplant. Recent work has demonstrated that the generation of organs from iPSCs is a future possibility. The development of embryonic-like organ structures bioengineered from iPSCs has been achieved, such as an early brain structure (cerebral organoids, bone, optic vesicle-like structures (eye, cardiac muscle tissue (heart, primitive pancreas islet cells, a tooth-like structure (teeth, and functional liver buds (liver. Thus, iPSC technology offers, in the future, the powerful and unique possibility to make body organs for transplantation removing the need for organ donation and immune suppressing drugs. Whilst it is clear that iPSCs are rapidly becoming the lead cell type for research into cell replacement therapy and body organ transplantation strategies in humans, it is not known whether (1 such transplants will stimulate host immune responses; and (2 whether this technology will be capable of the bioengineering of a complete and fully functional human organ. This review will not focus on reprogramming to iPSCs, of which a plethora of reviews can be found, but instead focus on the latest developments in direct reprogramming of cells, the bioengineering of body organs from iPSCs, and an analysis of the immune response induced by i

  18. Chemokine Receptor Signatures in Allogeneic Stem Cell Transplantation

    Science.gov (United States)

    2015-08-01

    No Impact of Pre-transplant Extramedullary Disease on Outcome” Bone Marrow Transplant (In Press) 7. Urbano Ispizua A, Pavletic S, Flowers ME, Klein...Transplants are performed in a new inpatient unit that was completely renovated with state-of-the- art equipment and inaugurated 2 years ago. The new unit is

  19. Hepatitis B-related events in autologous hematopoietic stem cell transplantation recipients

    Institute of Scientific and Technical Information of China (English)

    zcan; eneli; Zübeyde; Nur; zkurt; Kadir; Acar; Seyyal; Rota; Sahika; Zeynep; Aki; Zeynep; Arzu; Yegin; Münci; Yagci; Seren; zenirler; Gülsan; Türkz; Sucak

    2010-01-01

    AIM: To investigate the frequency of occult hepatitis B, the clinical course of hepatitis B virus (HBV) reactivation and reverse seroconversion and associated risk factors in autologous hematopoietic stem cell transplantation (HSCT) recipients. METHODS: This study was conducted in 90 patients undergoing autologous HSCT. Occult HBV infection was investigated by HBV-DNA analysis prior to transplantation, while HBV serology and liver function tests were screened prior to and serially after transplantation. HBV...

  20. Nutritional status and tissue composition in children after hematopoietic stem cell transplantation

    OpenAIRE

    A. Yu. Vashura; M. V. Konovalova; Skorobogatova, E. V.; S. V. Belmer; G. Ya. Tseytlin

    2014-01-01

    Hematopoietic stem cells transplantation (HSCT) is currently widely used for solid tumors, leukemia and autoimmune diseases therapy. Complications in post-transplant period, as well as specific therapy of these complications lead to nutritional status changes, which worsen post-transplant period and influence of outcome. To analyze nutritional status and tissue composition characteristics and determine the value of bioimpedance methods for complex examination of nutritional status in children...

  1. 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.

  2. Inhaled corticosteroids stabilize constrictive bronchiolitis after hematopoietic stem cell transplantation.

    Science.gov (United States)

    Bashoura, L; Gupta, S; Jain, A; Couriel, D R; Komanduri, K V; Eapen, G A; Safdar, A; Broglio, K R; Adachi, R; Dickey, B F

    2008-01-01

    Post transplantation constrictive bronchiolitis (PTCB) is the most common pulmonary complication among long-term survivors of allogeneic hematopoietic stem cell transplantation (HSCT). It is a late manifestation of GVHD. Its treatment with high-dose systemic corticosteroids and other immunosuppressive regimens is associated with multiple side effects. Topical corticosteroids are used for the treatment of other manifestations of GVHD to minimize these side effects. We conducted a retrospective analysis of a series of adult patients to evaluate the efficacy of high-dose inhaled corticosteroids in the treatment of PTCB. Seventeen patients with new-onset airflow obstruction were diagnosed with PTCB. Their forced expiratory volume in 1 s (FEV1) declined from a median of 84% (range, 56-119) before HSCT to 53% (26-82) after HSCT. All patients received inhaled fluticasone propionate 500-940 microg two times daily. Symptoms of airway obstruction improved and FEV1 stabilized 3-6 months after treatment. We conclude that high-dose inhaled corticosteroids may be effective in the treatment of PTCB and propose a plausible mechanism of its action. A prospective evaluation of its efficacy is warranted.

  3. Dyslipidemia after allogeneic hematopoietic stem cell transplantation: evaluation and management.

    Science.gov (United States)

    Griffith, Michelle L; Savani, Bipin N; Boord, Jeffrey B

    2010-08-26

    Currently, approximately 15,000 to 20,000 patients undergo allogeneic hematopoietic stem cell transplantation (HSCT) annually throughout the world, with the number of long-term survivors increasing rapidly. In long-term follow-up after transplantation, the focus of care moves beyond cure of the original disease to the identification and treatment of late effects after HSCT. One of the more serious complications is therapy-related cardiovascular disease. Long-term survivors after HSCT probably have an increased risk of premature cardiovascular events. Cardiovascular complications related to dyslipidemia and other risk factors account for a significant proportion of late nonrelapse morbidity and mortality. This review addresses the risk and causes of dyslipidemia and impact on cardiovascular complications after HSCT. Immunosuppressive therapy, chronic graft-versus-host disease, and other long-term complications influence the management of dyslipidemia. There are currently no established guidelines for evaluation and management of dyslipidemia in HSCT patients; in this review, we have summarized our suggested approach in the HSCT population.

  4. Intraportal mesenchymal stem cell transplantation prevents acute liver failure through promoting cell proliferation and inhibiting apoptosis

    Institute of Scientific and Technical Information of China (English)

    Jian-Feng Sang; Xiao-Lei Shi; Bin Han; Tao Huang; Xu Huang; Hao-Zhen Ren; Yi-Tao Ding

    2016-01-01

    BACKGROUND: Transplantation of mesenchymal stem cells (MSCs) has been regarded as a potential treatment for acute liver failure (ALF), but the optimal route was unknown. The present study aimed to explore the most effective MSCs trans-plantation route in a swine ALF model. METHODS: The swine ALF model induced by intravenous injection of D-Gal was treated by the transplantation of swine MSCs through four routes including intraportal injection (InP group), hepatic intra-arterial injection (AH group), pe-ripheral intravenous injection (PV group) and intrahepatic injection (IH group). The living conditions and survival time were recorded. Blood samples before and after MSCs trans-plantation were collected for the analysis of hepatic function. The histology of liver injury was interpreted and scored in terminal samples. Hepatic apoptosis was detected by TUNEL assay. Apoptosis and proliferation related protein expressions including cleaved caspase-3, survivin, AKT, phospho-AKT (Ser473), ERK and phospho-ERK (Tyr204) were analyzed by Western blotting. RESULTS: The average survival time of each group was 10.7 ± 1.6 days (InP), 6.0±0.9 days (AH), 4.7±1.4 days (PV), 4.3± 0.8 days (IH), respectively, when compared with the average survival time of 3.8±0.8 days in the D-Gal group. The sur-vival rates between the InP group and D-Gal group revealed a statistically signiifcant difference (P CONCLUSIONS: Intraportal injection was superior to other pathways for MSC transplantation. Intraportal MSC trans-plantation could improve liver function, inhibit apoptosis and prolong the survival time of swine with ALF. The transplanted MSCs may participate in liver regeneration via promoting cell proliferation and suppressing apoptosis during the initial stage of ALF.

  5. Generation of Transplantable Beta Cells for Patient-Specific Cell Therapy

    Directory of Open Access Journals (Sweden)

    Xiaojie Wang

    2012-01-01

    Full Text Available Islet cell transplantation offers a potential cure for type 1 diabetes, but it is challenged by insufficient donor tissue and side effects of current immunosuppressive drugs. Therefore, alternative sources of insulin-producing cells and isletfriendly immunosuppression are required to increase the efficiency and safety of this procedure. Beta cells can be transdifferentiated from precursors or another heterologous (non-beta-cell source. Recent advances in beta cell regeneration from somatic cells such as fibroblasts could circumvent the usage of immunosuppressive drugs. Therefore, generation of patient-specific beta cells provides the potential of an evolutionary treatment for patients with diabetes.

  6. Phagocytic activity of monocytes, their subpopulations and granulocytes during post-transplant adverse events after hematopoietic stem cell transplantation.

    Science.gov (United States)

    Döring, Michaela; Cabanillas Stanchi, Karin Melanie; Erbacher, Annika; Haufe, Susanne; Schwarze, Carl Philipp; Handgretinger, Rupert; Hofbeck, Michael; Kerst, Gunter

    2015-05-01

    Phagocytosis of granulocytes and monocytes presents a major mechanism that contributes to the clearance of pathogens and cell debris. We analyzed the phagocytic activity of the peripheral blood cell monocytes, three monocyte subpopulations and granulocytes before and up to one year after hematopoietic stem cell transplantation, as well as during transplant-related adverse events. 25 pediatric patients and young adults (median age of 11.0 years) with hemato-oncological malignancies and non malignancies were enrolled in the prospective study. Ingestion of fluorescence-labeled Escherichia coli bacteria was used to assess the phagocytic activity of monocytes and their subpopulations and granulocytes by means of flow cytometry in the patient group as well as in a control group (n=36). During sepsis, a significant increase of phagocytic activity of monocytes (P=0.0003) and a significant decrease of the phagocytic activity of granulocytes (P=0.0003) and the CD14+ CD16++ monocyte subpopulation (P=0.0020) occurred. At the onset of a veno-occlusive disease, a significant increase of phagocytic activity in the CD14++ CD16+ monocyte subpopulation (P=0.001) and a significant decrease in the phagocytic activity of the CD14++ CD16- monocyte subpopulation (P=0.0048) were observed. In conclusion, the phagocytic activity of monocytes, their subpopulations and granulocytes might be a useful and easy determinable parameter that enables identification of post-transplant complications after hematopoietic stem cell transplantation. The alterations of phagocytic activity contribute to the altered immune response that accompanies adverse events after hematopoietic stem cell transplantation.

  7. Haematopoietic Stem Cell Transplantation for Refractory Langerhans Cell Histiocytosis: Outcome by Intensity of Conditioning

    Science.gov (United States)

    Veys, Paul A.; Nanduri, Vasanta; Baker, K. Scott; He, Wensheng; Bandini, Giuseppe; Biondi, Andrea; Dalissier, Arnaud; Davis, Jeffrey H.; Eames, Gretchen M.; Egeler, R. Maarten; Filipovich, Alexandra H.; Fischer, Alain; Jürgens, Herbert; Krance, Robert; Lanino, Edoardo; Leung, Wing H.; Matthes, Susanne; Michel, Gérard; Orchard, Paul J.; Pieczonka, Anna; Ringdén, Olle; Schlegel, Paul G.; Sirvent, Anne; Vettenranta, Kim; Eapen, Mary

    2015-01-01

    Summary Patients with Langerhans cell histiocytosis (LCH) refractory to conventional chemotherapy have a poor outcome. There are currently two promising treatment strategies for high-risk patients: the first involves the combination of 2-chlorodeoxyadenosine and cytarbine; the other approach is allogeneic haematopoietic stem cell transplantation (HSCT). Here we evaluated 87 patients with high-risk LCH who were transplanted between 1990–2013. Prior to the year 2000, most patients underwent HSCT following myeloablative conditioning (MAC): only 5 of 20 patients (25%) survived with a high rate (55%) of transplant-related mortality (TRM). After the year 2000 an increasing number of patients underwent HSCT with reduced intensity conditioning (RIC): 49/67 (73%) patients survived, however, the improved survival was not overtly achieved by the introduction of RIC regimens with similar 3-year probability of survival after MAC (77%) and RIC transplantation (71%). There was no significant difference in TRM by conditioning regimen intensity but relapse rates were higher after RIC compared to MAC regimens (28% vs. 8%, p=0.02), although most patients relapsing after RIC transplantation could be salvaged with further chemotherapy. HSCT may be a curative approach in 3 out of 4 patients with high risk LCH refractory to chemotherapy: the optimal choice of HSCT conditioning remains uncertain. PMID:25817915

  8. Stem cell transplantation for treating Parkinson's disease Literature analysis based on the Web of Science

    Institute of Scientific and Technical Information of China (English)

    Runhui Li

    2012-01-01

    OBJECTIVE: To identify global research trends of stem cell transplantation for treating Parkinson's disease using a bibliometric analysis of the Web of Science. DATA RETRIEVAL: We performed a bibliometric analysis of data retrievals for stem cell transplantation for treating Parkinson's disease from 2002 to 2011 using the Web of Science. SELECTION CRITERIA: Inclusion criteria: (a) peer-reviewed articles on stem cell transplantation for treating Parkinson's disease which were published and indexed in the Web of Science; (b) type of articles: original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material and news items; (c) year of publication: 2002–2011. Exclusion criteria: (a) articles that required manual searching or telephone access; (b) we excluded documents that were not published in the public domain; (c) we excluded a number of corrected papers from the total number of articles.MAIN OUTCOME MEASURES: (1) Type of literature; (2) annual publication output; (3) distribution according to journals; (4) distribution according to subject areas; (5) distribution according to country; (6) distribution according to institution; (7) comparison of countries that published the most papers on stem cell transplantation from different cell sources for treating Parkinson's disease; (8) comparison of institutions that published the most papers on stem cell transplantation from different cell sources for treating Parkinson's disease in the Web of Science from 2002 to 2011; (9) comparison of studies on stem cell transplantation from different cell sources for treating Parkinson's diseaseRESULTS: In total, 1 062 studies on stem cell transplantation for treating Parkinson's disease appeared in the Web of Science from 2002 to 2011, almost one third of which were from American authors and institutes. The number of studies on stem cell transplantation for treating Parkinson's disease had gradually increased over the past 10 years

  9. The clinical application of mesenchymal stromal cells in hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Ke Zhao

    2016-05-01

    Full Text Available Abstract Mesenchymal stromal cells (MSCs are multipotent stem cells well known for repairing tissue, supporting hematopoiesis, and modulating immune and inflammation response. These outstanding properties make MSCs as an attractive candidate for cellular therapy in immune-based disorders, especially hematopoietic stem cell transplantation (HSCT. In this review, we outline the progress of MSCs in preventing and treating engraftment failure (EF, graft-versus-host disease (GVHD following HSCT and critically discuss unsolved issues in clinical applications.

  10. Induction of type I IFN is required for overcoming tumor-specific T-cell tolerance after stem cell transplantation.

    Science.gov (United States)

    Horkheimer, Ian; Quigley, Michael; Zhu, Jiangao; Huang, Xiaopei; Chao, Nelson J; Yang, Yiping

    2009-05-21

    Tumor-specific T-cell tolerance represents one major mechanism of tumor-induced immune evasion. Myeloablative chemotherapy with stem cell transplantation may offer the best chance of achieving a state of minimal residual disease and, thus, minimize tumor-induced immune evasion. However, studies have shown that tumor-specific T-cell tolerance persists after transplantation. Here, we showed that CD4(+)CD25(+) regulatory T (T(Reg)) cells play a critical role in tumor-specific CD8(+) T-cell tolerance after transplantation. Removal of T(Reg) cells from the donor lymphocyte graft did not overcome this tolerance because of rapid conversion of donor CD4(+)CD25(-) T cells into CD4(+)CD25(+)Foxp3(+) T(Reg) cells in recipients after transplantation, and depletion of T(Reg) cells in recipients was necessary for the reversal of tumor-specific tolerance. These results suggest that strategies capable of overcoming T-cell tolerance in recipients are required to promote antitumor immunity after transplantation. Toward this goal, we showed that dendritic cell (DC) vaccines coadministered with the TLR9 ligand, CpG could effectively overcome tumor-specific tolerance, leading to significant prolongation of tumor-free survival after transplantation. We further showed that CpG-induced type I interferon was critical for the reversal of tumor-specific tolerance in vivo. Collectively, these results may suggest effective immunotherapeutic strategies for treating cancer after stem cell transplantation.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  12. Role of CD8+ regulatory T cells in organ transplantation

    Directory of Open Access Journals (Sweden)

    Jiyan Su

    2014-01-01

    Full Text Available CD8 + T cells are regulatory T cells (Tregs that suppress both alloimmunity and autoimmunity in many animal models. This class of regulatory cells includes the CD8 + CD28 - , CD8 + CD103 + , CD8 + FoxP3 + and CD8 + CD122 + subsets. The mechanisms of action of these regulatory cells are not fully understood; however, the secretion of immunosuppressive cytokines, such as interleukin (IL-4, IL-10 and transforming growth factor beta (TGF-β as well as the direct killing of target cells via Fas L/Fas and the perforin/granzyme B pathways have been demonstrated in various models. Further studies are necessary to fully understand the mechanisms underlying the suppressive effects of Tregs and to provide experimental support for potential clinical trials. We recently observed that CD8 + CD122 + Tregs more potently suppressed allograft rejection compared to their CD4 + CD25 + counterparts, supporting the hypothesis that CD8 + Tregs may represent a new and promising Treg family that can be targeted to prevent allograft rejection in the clinic. In this review, we summarize the progress in the field during the past 7-10 years and discuss CD8 + Treg phenotypes, mechanisms of action, and their potential clinical applications; particularly in composite tissue transplants in burn and trauma patients.

  13. Lack of effect of intranigral transplants of a GABAergic cell line on absence seizures.

    Science.gov (United States)

    Castillo, Claudia G; Mendoza, Soledad; Saavedra, Josie; Giordano, Magda

    2010-08-01

    The substantia nigra pars reticulata (SNpr) is involved in controlling a variety of seizure phenomena. Intranigral transplants of GABAergic cells have been shown to decrease the severity of already established epileptic seizures, but the effects observed have been short-lived. This study evaluated the ability of intranigral transplants of GABA-producing cells to reduce spontaneous absence seizures in a genetic animal model for periods up to 3 months after transplantation. Intranigral transplants did not induce any behavioral deficits in the animals, and they did not form tumors; however, the transplants failed to decrease absence seizures in the genetic model. The assumed increase in intranigral levels of GABA after the transplants may be insufficient to counteract all the factors involved in generating the absence seizures; in this animal model, it may be necessary to further decrease nigral activity by implanting GABAergic cells in another area. These results bear down on the fact that cell transplants need to be tailored for each type of convulsive disorder in terms of the type of cells delivered and the location of the transplants.

  14. Intracranial transplantation of monocyte-derived multipotential cells enhances recovery after ischemic stroke in rats.

    Science.gov (United States)

    Hattori, Hidenori; Suzuki, Shigeaki; Okazaki, Yuka; Suzuki, Norihiro; Kuwana, Masataka

    2012-02-01

    Cell transplantation has emerged as a potential therapy to reduce the neurological deficits caused by ischemic stroke. We previously reported a primitive cell population, monocyte-derived multipotential cells (MOMCs), which can differentiate into mesenchymal, neuronal, and endothelial lineages. In this study, MOMCs and macrophages were prepared from rat peripheral blood and transplanted intracranially into the ischemic core of syngeneic rats that had undergone a left middle cerebral artery occlusion procedure. Neurological deficits, as evaluated by the corner test, were less severe in the MOMC-transplanted rats than in macrophage-transplanted or mock-treated rats. Histological evaluations revealed that the number of microvessels that had formed in the ischemic boundary area by 4 weeks after transplantation was significantly greater in the MOMC-transplanted rats than in the control groups. The blood vessel formation was preceded by the appearance of round CD31(+) cells, which we confirmed were derived from the transplanted MOMCs. Small numbers of bloodvessels incorporating MOMC-derived endothelial cells expressing a mature endothelial marker RECA-1 were detected at 4 weeks after transplantation. In addition, MOMCs expressed a series of angiogenic factors, including vascular endothelial growth factor, angiopoetin-1, and placenta growth factor (PlGF). These findings provide evidence that the intracranial delivery of MOMCs enhances functional recovery by promoting neovascularization in a rat model for ischemic stroke.

  15. Regulatory B cells and tolerance in transplantation: from animal models to human.

    Directory of Open Access Journals (Sweden)

    Melanie eChesneau

    2013-12-01

    Full Text Available Until recently, the role of B cells in transplantation was thought to be restricted to producing antibodies that have been clearly shown to be deleterious in the long term, but, in fact, B cells are also able to produce cytokine and to present antigen. Their role as regulatory cells in various pathological situations has also been highlighted, and their role in transplantation is beginning to emerge in animal, and also in human, models. This review summarizes the different studies in animals and humans that suggest a B-cell regulatory role in the transplant tolerance mechanisms.

  16. Autologous transplantation of bone marrow mesenchymal stem cells on diabetic patients with lower limb ischemia

    Institute of Scientific and Technical Information of China (English)

    Lu Debin; Jiang Youzhao; Liang Ziwen; Li Xiaoyan; Zhang Zhonghui; Chen Bing

    2008-01-01

    Objective: To study the efficacy and safety of autologous transplantation of bone marrow mesenchymal stem cells on diabetic patients with lower limb ischemia. Methods: Fifty Type 2 diabetic patients with lower limb ischemia were enrolled and randomized to either transplanted group or control group. Patients in both group received the same conventional treatment. Meanwhile, 20 ml bone marrow from each transplanted patient were collected, and the mesenchymal stem cells were separated by density gradient centrifugation and cultured in the medium with autologous serum. After three-weeks adherent culture in vitro, 7.32×108-5.61×109 mesenchymal stern cells were harvested and transplanted by multiple intramuscular and hypodermic injections into the impaired lower limbs. Results: At the end of 12-week follow-up, 5 patients were excluded from this study because of clinical worsening or failure of cell culture. Main ischemic symptoms, including rest pain and intermittent claudication, were improved significantly in transplanted patients. The ulcer healing rate of the transplanted group (15 of 18, 83.33%) was significantly higher than that of the control group (9 of 20, 45.00%, P=0.012).The mean of resting ankle-brachial index (ABI) in transplanted group significantly was increased from 0.61±0.09 to 0.74±0.11 (P<0.001). Magnetic resonance angiography (MRA) demonstrated that there were more patients whose score of new vessels exceeded or equaled to 2 in the transplant patients (11 of 15) than in control patients (2 of 14, P=0.001). Lower limb amputation rate was significantly lower in transplanted group than in the control group (P=0.040). No adverse effects was observed in transplanted group. Conclusion: These results indicate that the autologous transplantation of bone marrow mesenehymal stem cells relieves critical lower limb ischemia and promotes ulcers healing in Type 2 diabetic patients.

  17. Repopulation dynamics of single haematopoietic stem cells in mouse transplantation experiments: Importance of stem cell composition in competitor cells.

    Science.gov (United States)

    Ema, Hideo; Uchinomiya, Kouki; Morita, Yohei; Suda, Toshio; Iwasa, Yoh

    2016-04-07

    The transplantation of blood tissues from bone marrow into a lethally irradiated animal is an experimental procedure that is used to study how the blood system is reconstituted by haematopoietic stem cells (HSC). In a competitive repopulation experiment, a lethally irradiated mouse was transplanted with a single HSC as a test cell together with a number of bone marrow cells as competitor cells, and the fraction of the test cell progeny (percentage of chimerism) was traced over time. In this paper, we studied the stem cell kinetics in this experimental procedure. The balance between symmetric self-renewal and differentiation divisions in HSC determined the number of cells which HSC produce and the length of time for which HSC live after transplantation. The percentage of chimerism depended on the type of test cell (long-, intermediate-, or short-term HSC), as well as the type and number of HSC included in competitor cells. We next examined two alternative HSC differentiation models, one-step and multi-step differentiation models. Although these models differed in blood cell production, the percentage of chimerism appeared very similar. We also estimated the numbers of different types of HSC in competitor cells. Based on these results, we concluded that the experimental results inevitably include stochasticity with regard to the number and the type of HSC in competitor cells, and that, in order to detect different types of HSC, an appropriate number of competitor cells needs to be used in transplantation experiments.

  18. The origin of biliary ductular cells that appear in the spleen after transplantation of hepatocytes.

    Science.gov (United States)

    Fukuda, Kenji; Sugihara, Ayako; Nakasho, Keiji; Tsujimura, Tohru; Yamada, Naoko; Okaya, Atsuhito; Sakagami, Masafumi; Terada, Nobuyuki

    2004-01-01

    Transplantation of rat hepatocytes into the syngeneic rat spleen results in the appearance of cytokeration (CK)-19-positive biliary cells that form ductules. The exact origin of CK-19-positive cells is not known and the possibility that they are derived from biliary cells or precursors of oval cells in transplanted hepatocyte preparations has been raised. In the present study, we found that the number of CK-19-positive biliary cells increased rapidly after transplantation of hepatocytes, reached the maximum at 4 weeks, and then gradually decreased. However, a Ki-67 labeling index of CK-19-positive biliary cells was low and showed no significant changes throughout the experimental period. In addition, no or few CK-19-positive cells appeared in the spleen after transplantation of nonparenchymal liver cells enriched with biliary cells. These results showed that biliary cells were not the source of CK-19-positive cells in the spleen. Impairment of precursors of oval cells in the liver by administration of 4,4'-diaminodiphenylmethane 24 h before transplantation of hepatocytes did not prevent the appearance of CK-19-positive biliary cells in the spleen. Moreover, transplantation of nonparenchymal cells carrying an increased number of oval cells by means of treatment with 2-acetylaminofluorene and partial hepatectomy resulted in no appearance of CK-19-positive biliary cells in the spleen. These results ruled out oval cells as the origin of CK-19-positive biliary cells in the spleen. Because CK-19-positive biliary cells appeared in the spleen only when hepatocyte fractions were transplanted, we suggest transdifferentiation of heptocytes may be the mechanism by which CK-19-positive biliary cells are generated.

  19. Tandem autologous/reduced-intensity conditioning allogeneic stem-cell transplantation versus autologous transplantation in myeloma: long-term follow-up

    NARCIS (Netherlands)

    Bjorkstrand, B.; Iacobelli, S.; Hegenbart, U.; Gruber, A.; Greinix, H.; Volin, L.; Narni, F.; Musto, P.; Beksac, M.; Bosi, A.; Milone, G.; Corradini, P.; Goldschmidt, H.; Witte, T.J.M. de; Morris, C.; Niederwieser, D.; Gahrton, G.

    2011-01-01

    PURPOSE: Results of allogeneic stem-cell transplantation (allo) in myeloma are controversial. In this trial autologous stem-cell transplantation (auto) followed by reduced-intensity conditioning matched sibling donor allo (auto-allo) was compared with auto only in previously untreated multiple myelo

  20. Stem Cell Transplantation for Treatment of Primary Immunodeficiency Disorders

    Directory of Open Access Journals (Sweden)

    Susanna M. Müller Wilhelm Friedrich

    2005-03-01

    Full Text Available Primary Immunodeficiencies constitute a group of highly complex congenital disorders most of which are characterized by a very poor prognosis. Allogeneic hematopoietic stem cell transplantation (HSCT has become an established curative treatment approach in many of these disorders, which may be permanently corrected. In this presentation basic and practical aspects of HSCT are presented, with an emphasis on its application in lymphocyte disorders such as severe combined immunodeficiency (SCID. Optimal results and outcome of HSCT are highly dependant on early and correct diagnosis of these rare disorders, and HSCT should usually be applied early in the course of the disease in order to prevent irreversible complications from infections. Clinical results will be summarized based on recent analysis performed in large patient cohorts, which have shown steady improvements and have led to a marked change in the prognosis of patients with primary immunodeficiencies.

  1. Hematopoietic stem cell transplantation for primary immunodeficiency diseases.

    Science.gov (United States)

    Slatter, Mary A; Cant, Andrew J

    2011-11-01

    Hematopoietic stem cell transplantation (HSCT) is now highly successfully curing a widening range of primary immunodeficiencies (PIDs). Better tissue typing, matching of donors, less toxic chemotherapy, better virus detection and treatment, improved supportive care, and graft-versus-host disease prophylaxis mean up to a 90% cure for severe combined immunodeficiency patients and a 70-80% cure for other PIDs given a matched unrelated donor, and rising to 95% for young patients with specific PIDs, such as Wiskott-Aldrich syndrome. Precise molecular diagnosis, detailed data on prognosis, and careful pre-HSCT assessment of infective lung and liver damage will ensure an informed benefit analysis of HSCT and the best outcome. It is now recognized that the best treatment option for chronic granulomatous disease is HSCT, which can also be curative for CD40 ligand deficiency and complex immune dysregulation disorders.

  2. Parental caregiving of children prior to hematopoietic stem cell transplant.

    Science.gov (United States)

    Rodday, Angie Mae; Pedowitz, Elizabeth J; Mayer, Deborah K; Ratichek, Sara J; Given, Charles W; Parsons, Susan K

    2012-08-01

    Using the Caregiver Reaction Assessment (CRA), we assessed positive reactions and burdens of the caregiving experience among parental caregivers (n = 189) of children scheduled to undergo hematopoietic stem cell transplant. Although widely used in non-parental caregivers, the CRA has not been used in parents of pediatric patients. Reliability (Cronbach's alpha: .72-.81 vs. .63) and concurrent validity (correlation: .41-.61 vs. .28) were higher for negatively framed than positively framed subscales. Results indicate that the caregiving experience is complex. The parents experienced high caregiver's esteem and moderate family support, but also negative impacts on finances and schedule, and to a lesser degree, health. Compared to non-parental caregivers, parental caregivers experienced higher esteem and more impact on finances and schedule.

  3. B Cell Depletion: Rituximab in Glomerular Disease and Transplantation

    Directory of Open Access Journals (Sweden)

    S. Marinaki

    2013-12-01

    Full Text Available B cells play a central role in the pathogenesis of many autoimmune diseases. Selective targeting can be achieved with the use of the monoclonal antibody rituximab. In addition to being a drug for non-Hodgkin's lymphoma, rituximab is also an FDA-approved treatment for refractory rheumatoid arthritis and, since recently, ANCA vasculitis. It has shown efficacy in many autoimmune diseases. This review will discuss current evidence and the rationale of the use of rituximab in glomerular diseases, including randomized controlled trials. The focus will be on the use of rituximab in idiopathic membranous nephropathy, systemic lupus erythematosus and ANCA-associated vasculitis. The emerging role of rituximab in renal transplantation, where it seems to be important for the desensitization protocols for highly sensitized patients as well as for the preconditioning of ABO-incompatible recipients and the treatment of antibody-mediated rejection, will also be addressed.

  4. Mixed germ-cell testicular tumor in a liver transplant recipient

    Directory of Open Access Journals (Sweden)

    Mehdi Salehipour

    2012-01-01

    Full Text Available The development of malignancies after solid organ transplants is a well-known complication. Cancer is associated with significant consequences for the organ transplant patient. It is expected that cancer will surpass cardiovascular complications as the leading cause of death in transplant patients within the next few years. We report on a 36-year-old male patient who developed mixed germ-cell testicular tumor seven years after liver transplantation for alcoholic cirrhosis. He was treated with orchiectomy, retroperitoneal lymph node dissection and post-operative chemotherapy.

  5. Transplante de células-tronco hematopoéticas (TCTH em doenças falciformes Hematopoietic stem cell transplantation in sickle cell anemia

    Directory of Open Access Journals (Sweden)

    Fabiano Pieroni

    2007-09-01

    Full Text Available O único tratamento curativo para pacientes com doença falciforme é o transplante de células tronco hematopoéticas (TCTH. Neste artigo sumarizamos os resultados do TCTH em pacientes falciformes publicados na literatura e a experiência brasileira. As indicações atuais para o TCTH nestes pacientes serão discutidas.The only curative treatment approach for patients with sickle cell anemia is allogeneic stem cell transplantation. In this article we will review the published data about stem cell transplantation in patients with sickle cell disease and the small Brazilian experience in this field. The possible indications for stem cell patients will be discussed.

  6. [Autologous stem cell transplantation for autoimmune diseases: recommendations from the SFGM-TC].

    Science.gov (United States)

    Farge, D; Terriou, L; Badoglio, M; Cras, A; Desreumaux, P; Hadj-Khelifa, S; Marjanovic, Z; Moisan, A; Dulery, R; Faucher, C; Hij, A; Martin, T; Vermersch, P; Yakoub-Agha, I

    2014-08-01

    Autologous hematopoietic stem cell transplantation is a valid alternative to immunosuppressive treatment in patients with auto-immune disease; however, the role of this approach remains subject to debate. In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC) set up its fourth annual series of workshops which brought together practitioners from all of its member centers. These workshops took place in September 2013 in Lille. In this article we give an overview regarding the indications of autologous stem cell transplantation in auto-immune diseases as well as recommendations regarding post-transplant follow-up of patients.

  7. 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.

  8. Hematopoietic stem cell transplantation in sickle cell disease: patient selection and special considerations

    Directory of Open Access Journals (Sweden)

    Bhatia M

    2015-07-01

    Full Text Available Monica Bhatia,1 Sujit Sheth21Division of Pediatric Hematology/Oncology/Stem Cell Transplantation, Columbia University Medical Center, 2Division of Pediatric Hematology and Oncology, Weill Cornell Medical College, New York, NY, USAAbstract: Hematopoietic stem cell transplantation remains the only curative treatment currently in use for patients with sickle cell disease (SCD. The first successful hematopoietic stem cell transplantation was performed in 1984. To date, approximately 1,200 transplants have been reported. Given the high prevalence of this disorder in Africa, and its emergence in the developed world through immigration, this number is relatively small. There are many reasons for this; primary among them are the availability of a donor, the risks associated with this complex procedure, and the cost and availability of resources in the developing world. Of these, it is fair to say that the risks associated with the procedure have steadily decreased to the point where, if currently performed in a center with experience using a matched sibling donor, overall survival is close to 100% and event-free survival is over 90%. While there is little controversy around offering hematopoietic stem cell transplantation to symptomatic SCD patients with a matched sibling donor, there is much debate surrounding the use of this modality in “less severe” patients. An overview of the current state of our understanding of the pathology and treatment of SCD is important to show that our current strategy is not having the desired impact on survival of homozygous SCD patients, and should be changed to significantly impact the small proportion of these patients who have matched siblings and could be cured, especially those without overt clinical manifestations. Both patient families and providers must be made to understand the progressive nature of SCD, and should be encouraged to screen full siblings of patients with homozygous SCD for their potential to

  9. Stem cell-paved biobridges facilitate stem transplant and host brain cell interactions for stroke therapy.

    Science.gov (United States)

    Duncan, Kelsey; Gonzales-Portillo, Gabriel S; Acosta, Sandra A; Kaneko, Yuji; Borlongan, Cesar V; Tajiri, Naoki

    2015-10-14

    Distinguished by an infarct core encased within a penumbra, stroke remains a primary source of mortality within the United States. While our scientific knowledge regarding the pathology of stroke continues to improve, clinical treatment options for patients suffering from stroke are extremely limited. Tissue plasminogen activator (tPA) remains the sole FDA-approved drug proven to be helpful following stroke. However, due to the need to administer the drug within 4.5h of stroke onset its usefulness is constrained to less than 5% of all patients suffering from ischemic stroke. One experimental therapy for the treatment of stroke involves the utilization of stem cells. Stem cell transplantation has been linked to therapeutic benefit by means of cell replacement and release of growth factors; however the precise means by which this is accomplished has not yet been clearly delineated. Using a traumatic brain injury model, we recently demonstrated the ability of transplanted mesenchymal stromal cells (MSCs) to form a biobridge connecting the area of injury to the neurogenic niche within the brain. We hypothesize that MSCs may also have the capacity to create a similar biobridge following stroke; thereby forming a conduit between the neurogenic niche and the stroke core and peri-infarct area. We propose that this biobridge could assist and promote interaction of host brain cells with transplanted stem cells and offer more opportunities to enhance the effectiveness of stem cell therapy in stroke. This article is part of a Special Issue entitled SI: Cell Interactions In Stroke.

  10. Edaravone combined with Schwann cell transplantation may repair spinal cord injury in rats

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    Shu-quan Zhang

    2015-01-01

    Full Text Available Edaravone has been shown to delay neuronal apoptosis, thereby improving nerve function and the microenvironment after spinal cord injury. Edaravone can provide a favorable environment for the treatment of spinal cord injury using Schwann cell transplantation. This study used rat models of complete spinal cord transection at T 9. Six hours later, Schwann cells were transplanted in the head and tail ends of the injury site. Simultaneously, edaravone was injected through the caudal vein. Eight weeks later, the PKH-26-labeled Schwann cells had survived and migrated to the center of the spinal cord injury region in rats after combined treatment with edaravone and Schwann cells. Moreover, the number of PKH-26-labeled Schwann cells in the rat spinal cord was more than that in rats undergoing Schwann cell transplantation alone or rats without any treatment. Horseradish peroxidase retrograde tracing revealed that the number of horseradish peroxidase-positive nerve fibers was greater in rats treated with edaravone combined withSchwann cells than in rats with Schwann cell transplantation alone. The results demonstrated that lower extremity motor function and neurophysiological function were better in rats treated with edaravone and Schwann cells than in rats with Schwann cell transplantation only. These data confirmed that Schwann cell transplantation combined with edaravone injection promoted the regeneration of nerve fibers of rats with spinal cord injury and improved neurological function.

  11. Transplantation of fetal liver epithelial progenitor cells ameliorates experimental liver fibrosis in mice

    Institute of Scientific and Technical Information of China (English)

    Jin-Fang Zheng; Li-Jian Liang; Chang-Xiong Wu; Jin-Song Chen; Zhen-Sheng Zhang

    2006-01-01

    AIM: To investigate the effect of transplanted fetal liver epithelial progenitor (FLEP) cells on liver fibrosis in mice.METHODS: FLEP cells were isolated from embryonal day (ED) 14 BALB/c mice and transplanted into female syngenic BALB/c mice (n = 60). After partial hepatectomy (PH), diethylnitrosamine (DEN) was administered to induce liver fibrosis. Controls received FLEP cells and non-supplemented drinking water, the model group received DEN-spiked water, and the experimental group received FLEP cells and DEN.Mice were killed after 1, 2, and 3 mo, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronic acid (HA), and laminin (LN) in serum,and hydroxyproline (Hyp) content in liver were assessed.Alpha-smooth muscle actin (α-SMA) of liver was tested by immunohistochemistry. Transplanted male mice FLEP cells were identified by immunocytochemistry for sry (sex determination region for Y chromosome) protein.RESULTS: Serum ALT, AST, HA, and LN were markedly reduced by transplanted FLEP cells. Liver Hyp content and α-SMA staining in mice receiving FLEP cells were lower than that of the model group, which was consistent with altered liver pathology. Transplanted cells proliferated and differentiated into hepatocytes and bile duct epithelial cells with 30%-50% repopulation in the liver fibrosis induced by DEN after 3 mo.CONCLUSION: Transplanted FLEP cells proliferate and differentiate into hepatocytes and bile duct epithelial cells with high repopulation capacity in the fiberized liver induced by DEN, which restores liver function and reduces liver fibrosis.

  12. Autologous Bone Marrow Mononuclear Cells Intrathecal Transplantation in Chronic Stroke

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    Alok Sharma

    2014-01-01

    Full Text Available Cell therapy is being widely explored in the management of stroke and has demonstrated great potential. It has been shown to assist in the remodeling of the central nervous system by inducing neurorestorative effect through the process of angiogenesis, neurogenesis, and reduction of glial scar formation. In this study, the effect of intrathecal administration of autologous bone marrow mononuclear cells (BMMNCs is analyzed on the recovery process of patients with chronic stroke. 24 patients diagnosed with chronic stroke were administered cell therapy, followed by multidisciplinary neurorehabilitation. They were assessed on functional independence measure (FIM objectively, along with assessment of standing and walking balance, ambulation, and hand functions. Out of 24 patients, 12 improved in ambulation, 10 in hand functions, 6 in standing balance, and 9 in walking balance. Further factor analysis was done. Patients of the younger groups showed higher percentage of improvement in all the areas. Patients who underwent cell therapy within 2 years after the stroke showed better changes. Ischemic type of stroke had better recovery than the hemorrhagic stroke. This study demonstrates the potential of autologous BMMNCs intrathecal transplantation in improving the prognosis of functional recovery in chronic stage of stroke. Further clinical trials are recommended. This trial is registered with NCT02065778.

  13. Pregnancy after allogeneic hematopoietic stem cell transplantation in a Fanconi anemia patient

    Science.gov (United States)

    Atashkhoei, Simin; Fakhari, Solmaz; Bilehjani, Eissa; Farzin, Haleh

    2017-01-01

    Pregnancy in patients with Fanconi anemia (FA) is rare. However, there are reports of successful pregnancy in Fanconi patients after bone marrow transplantation (BMT, hematopoietic stem cell transplantation). We describe the case of a term pregnant woman with FA who was treated with BMT 2 years earlier. She underwent successful delivery with cesarean section using spinal anesthesia without any complications.

  14. Hematopoietic reconstitution on the prognosis of hematological malignancies after allogenceic hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    张燕

    2012-01-01

    Objective To analyze the impact of the time to hematopoietic reconstitution on the prognosis of hematological malignancies after allogeneic hematopoietic stem cell transplantation(allo-HSCT) . Methods 173 patients with hematological malignancies treated with allo-HSCT (excluding umbilical cord blood transplantation)

  15. Oral cyclosporine A treatment is feasible after myeloablative conditioning in allogeneic hematopoietic stem cell transplantation

    DEFF Research Database (Denmark)

    Nygaard, M; Hovgaard, D; Schjødt, I M;

    2015-01-01

    underwent myeloablative hematopoietic stem cell transplantation. Twenty-one patients (44%) tolerated CsA orally throughout the transplantation period without increased incidence of acute graft versus host disease(aGVHD). Low concentration of CsA in week 2 was associated with increased incidence of a...

  16. Effectiveness of Partner Social Support Predicts Enduring Psychological Distress after Hematopoietic Stem Cell Transplantation

    Science.gov (United States)

    Rini, Christine; Redd, William H.; Austin, Jane; Mosher, Catherine E.; Meschian, Yeraz Markarian; Isola, Luis; Scigliano, Eileen; Moskowitz, Craig H.; Papadopoulos, Esperanza; Labay, Larissa E.; Rowley, Scott; Burkhalter, Jack E.; Schetter, Christine Dunkel; DuHamel, Katherine N.

    2011-01-01

    Objective: Hematopoietic stem cell transplant (HSCT) survivors who are 1 to 3 years posttransplant are challenged by the need to resume valued social roles and activities--a task that may be complicated by enduring transplant-related psychological distress common in this patient population. The present study investigated whether transplant…

  17. Autologous stem cell transplantation in treatment of aggressive non-Hodgkin's lymphoma

    NARCIS (Netherlands)

    Kluin-Nelemans, Hanneke

    2002-01-01

    There is no doubt that autologous stem cell transplantation is useful for patients with relapsed aggressive non-Hodgkin's lymphoma if they are responsive to the chemotherapy given before the transplantation. A small subset of patients with primary refractory disease still profits from this high dose

  18. Introduction of a quality management system and outcome after hematopoietic stem-cell transplantation

    NARCIS (Netherlands)

    Gratwohl, A.; Brand, R.; Niederwieser, D.; Baldomero, H.; Chabannon, C.; Cornelissen, J.; Witte, T.J.M. de; Ljungman, P.; McDonald, F.; McGrath, E.; Passweg, J.; Peters, C.; Rocha, V.; Slaper-Cortenbach, I.; Sureda, A.; Tichelli, A.; Apperley, J.

    2011-01-01

    PURPOSE: A comprehensive quality management system called JACIE (Joint Accreditation Committee International Society for Cellular Therapy and the European Group for Blood and Marrow Transplantation), was introduced to improve quality of care in hematopoietic stem-cell transplantation (HSCT). We ther

  19. Introduction of a Quality Management System and Outcome After Hematopoietic Stem-Cell Transplantation

    NARCIS (Netherlands)

    Gratwohl, Alois; Brand, Ronald; Niederwieser, Dietger; Baldomero, Helen; Chabannon, Christian; Cornelissen, Jan; de Witte, Theo; Ljungman, Per; McDonald, Fiona; McGrath, Eoin; Passweg, Jakob; Peters, Christina; Rocha, Vanderson; Slaper-Cortenbach, Ineke; Sureda, Anna; Tichelli, Andre; Apperley, Jane

    2011-01-01

    Purpose A comprehensive quality management system called JACIE (Joint Accreditation Committee International Society for Cellular Therapy and the European Group for Blood and Marrow Transplantation), was introduced to improve quality of care in hematopoietic stem-cell transplantation (HSCT). We there

  20. Nutritional assessment as predictor of complications after hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Marcela Espinoza

    2016-02-01

    Full Text Available ABSTRACT Introduction: Nutritional support is pivotal in patients submitted to hematopoietic stem cell transplantation. Nutritional status has been associated with time of engraftment and infection rates. In order to evaluate the association between nutritional parameters and clinical outcomes after transplantation a cohort of transplant patients was retrospectively evaluated. Methods: All 50 patients transplanted between 2011 and 2014 were included. The nutritional status before transplantation, ten days after transplantation and before discharge was assessed including anthropometry, body mass index, albumin, prealbumin and total urinary nitrogen. Results: The median follow-up time was 41 months and the median age of patients was 41 years. Thirty-two underwent allogeneic and 18 autologous transplants. Diagnoses included acute leukemias (n = 27, lymphoma (n = 7, multiple myeloma (n = 13, and aplastic anemia (n = 3. Thirty-seven patients developed mucositis (three Grade 1, 15 Grade 2, 18 Grade 3 and one Grade 4, and twenty-two allogeneic, and five autologous transplant patients required total parenteral nutrition. Albumin and total urinary nitrogen were associated with length of hospital stay and platelet and neutrophil engraftment. None of the nutritional parameters evaluated were associated with overall survival. Non-relapse mortality was 14% and overall survival was 79% at 41 months of follow-up. Conclusions: After hematopoietic stem cell transplantation, high catabolism was associated with longer length of hospital stay, the need of total parenteral nutrition and platelet and neutrophil engraftment times. Nutritional parameters were not associated with overall survival.

  1. American Society of Blood and Marrow Transplant, European Society of Blood and Marrow Transplantation, Blood and Marrow Transplant Clinical Trials Network and International Myeloma Working Group Consensus Conference on Salvage Hematopoietic Cell Transplantation in Patients with Relapsed Multiple

    DEFF Research Database (Denmark)

    Giralt, S; Garderet, L; Durie, B

    2015-01-01

    not been extensively studied in MM patients relapsing after primary therapy. The International Myeloma Working Group together with the Blood and Marrow Transplant Clinical Trials Network, the American Society of Blood and Marrow Transplantation, and the European Society of Blood and Marrow Transplantation...... convened a meeting of MM experts to: (1) summarize current knowledge regarding the role of autologous or allogeneic HCT in MM patients progressing after primary therapy, (2) propose guidelines for the use of salvage HCT in MM, (3) identify knowledge gaps, (4) propose a research agenda, and (5) develop...... autologous HCT in patients with MM relapsing after primary therapy comparing it to "best non-HCT" therapy. The expert committee also underscored the importance of collecting enough hematopoietic stem cells to perform 2 transplantations early in the course of the disease. Regarding allogeneic HCT, the expert...

  2. Transplantation of rat hepatic stem-like (HSL) cells with collagen matrices.

    Science.gov (United States)

    Ueno, Yasuharu; Nagai, Hirokazu; Watanabe, Go; Ishikawa, Kiyoshi; Yoshikawa, Kiwamu; Koizumi, Yukio; Kameda, Takashi; Sugiyama, Toshihiro

    2005-12-01

    Organ restitution using somatic stem cells is of great clinical interest. Recent advances in the field of tissue engineering have demonstrated that the use of collagen matrices as scaffolds facilitates tissue reconstruction. Here, we examine the efficacy of transplantation of HSL cells, a previously established liver epithelial cell line with a potential for differentiation, using collagen scaffolds. To this end, HSL cells were transplanted into Nagase's analbuminemic rat with spongy or gelatinous type I collagen matrices. Consequently, immunohistochemical analyses and genomic PCR experiments revealed engraftment of the transplanted cells. Furthermore, the levels of serum albumin in recipient rats were found to increase up to 2.5-fold relative to controls after transplantation. These findings suggest that HSL cells are able to differentiate into functional hepatocytes in vivo, and that biodegradable collagen matrices enhance this phenomenon by providing an appropriate microenvironment for hepatocytic repopulation.

  3. New directions for rabbit antithymocyte globulin (Thymoglobulin(®)) in solid organ transplants, stem cell transplants and autoimmunity.

    Science.gov (United States)

    Mohty, Mohamad; Bacigalupo, Andrea; Saliba, Faouzi; Zuckermann, Andreas; Morelon, Emmanuel; Lebranchu, Yvon

    2014-09-01

    In the 30 years since the rabbit antithymocyte globulin (rATG) Thymoglobulin(®) was first licensed, its use in solid organ transplantation and hematology has expanded progressively. Although the evidence base is incomplete, specific roles for rATG in organ transplant recipients using contemporary dosing strategies are now relatively well-identified. The addition of rATG induction to a standard triple or dual regimen reduces acute cellular rejection, and possibly humoral rejection. It is an appropriate first choice in patients with moderate or high immunological risk, and may be used in low-risk patients receiving a calcineurin inhibitor (CNI)-sparing regimen from time of transplant, or if early steroid withdrawal is planned. Kidney transplant patients at risk of delayed graft function may also benefit from the use of rATG to facilitate delayed CNI introduction. In hematopoietic stem cell transplantation, rATG has become an important component of conventional myeloablative conditioning regimens, following demonstration of reduced acute and chronic graft-versus-host disease. More recently, a role for rATG has also been established in reduced-intensity conditioning regimens. In autoimmunity, rATG contributes to the treatment of severe aplastic anemia, and has been incorporated in autograft projects for the management of conditions such as multiple sclerosis, Crohn's disease, and systemic sclerosis. Finally, research is underway for the induction of tolerance exploiting the ability of rATG to induce immunosuppresive cells such as regulatory T-cells. Despite its long history, rATG remains a key component of the immunosuppressive armamentarium, and its complex immunological properties indicate that its use will expand to a wider range of disease conditions in the future.

  4. Stem cell sources for clinical islet transplantation in type 1 diabetes: embryonic and adult stem cells.

    Science.gov (United States)

    Miszta-Lane, Helena; Mirbolooki, Mohammadreza; James Shapiro, A M; Lakey, Jonathan R T

    2006-01-01

    Lifelong immunosuppressive therapy and inadequate sources of transplantable islets have led the islet transplantation benefits to less than 0.5% of type 1 diabetics. Whereas the potential risk of infection by animal endogenous viruses limits the uses of islet xeno-transplantation, deriving islets from stem cells seems to be able to overcome the current problems of islet shortages and immune compatibility. Both embryonic (derived from the inner cell mass of blastocysts) and adult stem cells (derived from adult tissues) have shown controversial results in secreting insulin in vitro and normalizing hyperglycemia in vivo. ESCs research is thought to have much greater developmental potential than adult stem cells; however it is still in the basic research phase. Existing ESC lines are not believed to be identical or ideal for generating islets or beta-cells and additional ESC lines have to be established. Research with ESCs derived from humans is controversial because it requires the destruction of a human embryo and/or therapeutic cloning, which some believe is a slippery slope to reproductive cloning. On the other hand, adult stem cells are already in some degree specialized, recipients may receive their own stem cells. They are flexible but they have shown mixed degree of availability. Adult stem cells are not pluripotent. They may not exist for all organs. They are difficult to purify and they cannot be maintained well outside the body. In order to draw the future avenues in this field, existent discrepancies between the results need to be clarified. In this study, we will review the different aspects and challenges of using embryonic or adult stem cells in clinical islet transplantation for the treatment of type 1 diabetes.

  5. A Biological Pacemaker Restored by Autologous Transplantation of Bone Marrow Mesenchymal Stem Cells

    Institute of Scientific and Technical Information of China (English)

    REN Xiao-qing; PU Jie-lin; ZHANG Shu; MENG Liang; WANG Fang-zheng

    2008-01-01

    Objective:To restore cardiac autonomic pace function by autologous transplantation and committed differentiation of bone marrow mesenchymal stem cells, and explore the technique for the treatment of sick sinus syndrome. Methods:Mesenchymal stem cells isolated from canine bone marrow were culture-expanded and differentiated in vitro by 5-azacytidine. The models of sick sinus syndrome in canines were established by ablating sinus node with radio-frequency technique. Differentiated mesenchymal stem cells labeled by BrdU were autologously transplanted into sinus node area through direct injection. The effects of autologous transplantation of mesenchymal stem cells on cardiac autonomic pace function in sick sinus syndrome models were evaluated by electrocardiography, pathologic and immunohistochemical staining technique.Results:There was distinct improvement on pace function of sick sinus syndrome animal models while differentiated mesenchymal stem cells were auto-transplanted into sinus node area. Mesenchymal stem cells transplanted in sinus node area were differentiated into similar sinus node cells and endothelial cells in vivo, and established gap junction with native cardiomyocytes. Conclusion:The committed-induced mesenchymal stem cells transplanted into sinus node area can differentiate into analogous sinus node cells and improve pace function in canine sick sinus syndrome models.

  6. The association of killer cell immunoglobulin like receptor gene polylmorphism with cytomegalovirus infection after hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    吴小津

    2013-01-01

    Objective To explore the influence of the killer cell immunoglobulin like receptor(KIR)gene polymorphism on cytomegalovirus(CMV)infection and pathogenesis after hematopoietic stem cell transplantation(HSCT)

  7. Transplanted microvascular endothelial cells promote oligodendrocyte precursor cell survival in ischemic demyelinating lesions.

    Science.gov (United States)

    Iijima, Keiya; Kurachi, Masashi; Shibasaki, Koji; Naruse, Masae; Puentes, Sandra; Imai, Hideaki; Yoshimoto, Yuhei; Mikuni, Masahiko; Ishizaki, Yasuki

    2015-11-01

    We previously showed that transplantation of brain microvascular endothelial cells (MVECs) greatly stimulated remyelination in the white matter infarct of the internal capsule (IC) induced by endothelin-1 injection and improved the behavioral outcome. In the present study, we examined the effect of MVEC transplantation on the infarct volume using intermittent magnetic resonance image and on the behavior of oligodendrocyte lineage cells histochemically. Our results in vivo show that MVEC transplantation reduced the infarct volume in IC and apoptotic death of oligodendrocyte precursor cells (OPCs). These results indicate that MVECs have a survival effect on OPCs, and this effect might contribute to the recovery of the white matter infarct. The conditioned-medium from cultured MVECs reduced apoptosis of cultured OPCs, while the conditioned medium from cultured fibroblasts did not show such effect. These results suggest a possibility that transplanted MVECs increased the number of OPCs through the release of humoral factors that prevent their apoptotic death. Identification of such humoral factors may lead to the new therapeutic strategy against ischemic demyelinating diseases.

  8. A Case of Giant Cell Hepatitis Recurring after Liver Transplantation and Treated with Ribavirin

    Directory of Open Access Journals (Sweden)

    Ziad Hassoun

    2000-01-01

    Full Text Available A patient who underwent orthotopic liver transplantation for giant cell hepatitis with cirrhosis and in whom giant cell hepatitis recurred twice after orthotopic liver transplantation is reported. He was treated with ribavirin with an excellent result. The literature on this subject is reviewed. This observation clearly confirms the efficacy of ribavirin for the treatment of giant cell hepatitis, thus providing evidence for its viral origin.

  9. Recurrent myelitis after allogeneic stem cell transplantation. Report of two cases

    Directory of Open Access Journals (Sweden)

    Voß Martin

    2010-09-01

    Full Text Available Abstract Background Allogeneic and autologous haematopoietic stem cell transplantation are established treatment options for haematological malignancies and may possibly be employed to treat a range of genetic and autoimmune diseases. Case presentation We report two patients who developed an acute myelitis within their thoracic spinal cord after allogeneic stem cell transplantation. Myelitis in these patients was not related to graft versus host disease or immune reconstitution and was responsive to intravenous methylprednisolone and cyclophosphamide. Conclusions Myelitis is a possibly disabling consequence of haematopoietic stem cell transplantation.

  10. Transplanted adipose-derived stem cells delay D-galactose-induced aging in rats

    Institute of Scientific and Technical Information of China (English)

    Chun Yang; Ou Sha; Jingxing Dai; Lin Yuan; Dongfei Li; Zhongqiu Wen; Huiying Yang; Meichun Yu; Hui Tao; Rongmei Qu; Yikuan Du; Yong Huang

    2011-01-01

    To investigate the effects of allogeneically transplanted, adipose-derived stem cells in aging rats, in the present study, we established a rat model of subacute aging using continuous subcutaneous injections of D-galactose. Two weeks after the adipose-derived stem cells transplantations, serum superoxide dismutase activity was significantly increased, malondialdehyde content was significantly reduced, hippocampal neuronal degeneration was ameliorated, the apoptotic index of hippocampal neurons was decreased, and learning and memory function was significantly improved in the aging rats. These results indicate that allogeneic transplantation of adipose-derived stem cells may effectively delay D-galactose-induced aging.

  11. Magentic Cell labeling of primary and stem cell-derived pig hepatocytes for MRI-based cell tracking of heptocytes transplantation

    Science.gov (United States)

    Pig hepatocytes are an important investigational tool for optimizing hepatocyte transplantation schemes in both allogeneic and xenogeneic transplant scenarios. MRI can be used to serially monitor the transplanted cells, but only if the hepatocytes can be labeled with a magnetic particle. In this wo...

  12. Comparison of outcomes after unrelated cord blood and unmanipulated haploidentical stem cell transplantation in adults with acute leukemia

    DEFF Research Database (Denmark)

    Ruggeri, A; Labopin, M; Sanz, G;

    2015-01-01

    Outcomes after unmanipulated haploidentical stem cell transplantation (Haplo) and after unrelated cord blood transplantation (UCBT) are encouraging and have become alternative options to treat patients with high-risk acute leukemia without human leukocyte antigen (HLA) matched donor. We compared ...

  13. Targeting the bone marrow: applications in stem cell transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Orchard, K. [Southampton University Hospital Trust, Southampton (United Kingdom). Department of Haematology; Cooper, M. [St. Bartholomew' s Hospital, London (United Kingdom). Pharmacy Department

    2004-12-01

    Therapeutic doses of radiation cab be selectively directed to the bone marrow either directly using vectors that bind to myeloid and/or lymphoid specific antigens or indirectly by targeting bone matrix. The combination of an accessible target tissue and relatively radiation sensitive malignant cells favours the use of targeted radiotherapy in the treatment of haematopoietic malignancies. Dose escalation of targeted radiation can increase tumour cell destruction and has led to the use of myelosuppressive and possibly myeloablative doses of targeted radiation. A natural development has been the use of targeted radiation in conditioning prior to haematopoietic stem cell transplantation (HSCT). Several groups are actively exploring the use of targeted radiotherapy in the context of HSCT as treatment for haematological malignancies. Although no randomised trials using targeted radiotherapy in HSCT have been published, phase I and II trials have shown very encouraging results stimulating further clinical research in this field. After more than a decade of translational research the optimal combination of therapeutic radioisotope and vector has not been determined. This review summarises the clinical experience of targeted radiotherapy in HSCT and discusses the problems that still need to be solved to maximise the potential of this new treatment modality in HSCT.

  14. Combination of edaravone and neural stem cell transplantation repairs injured spinal cord in rats.

    Science.gov (United States)

    Song, Y Y; Peng, C G; Ye, X B

    2015-12-29

    This study sought to observe the effect of the combination of edaravone and neural stem cell (NSC) transplantation on the repair of complete spinal cord transection in rats. Eighty adult female Sprague-Dawley (SD) rats were used to establish the injury model of complete spinal cord transection at T9. Animals were divided randomly into four groups (N = 20 each): control, edaravone, transplantation, and edaravone + transplantation. The recovery of spinal function was evaluated with the Basso, Beattie, Bresnahan (BBB) rating scale on days 1, 3, and 7 each week after the surgery. After 8 weeks, the BBB scores of the control, edaravone, transplantation, and combination groups were 4.21 ± 0.11, 8.46 ± 0.1, 8.54 ± 0.13, and 11.21 ± 0.14, respectively. At 8 weeks after surgery, the spinal cord was collected; the survival and transportation of transplanted cells were observed with PKH-26 labeling, and the regeneration and distribution of spinal nerve fibers with fluorescent-gold (FG) retrograde tracing. Five rats died due to the injury. PKH-26-labeled NSCs had migrated into the spinal cord. A few intact nerve fibers and pyramidal neurons passed the injured area in the transplantation and combination groups. The numbers of PKH-26-labeled cells and FG-labeled nerve fibers were in the order: combination group > edaravone group and transplantation group > control group (P injured areas; edaravone with NSC transplantation can improve the effectiveness of spinal cord injury repair in rats.

  15. Restoration of spermatogenesis after transplantation of c-Kit positive testicular cells in the fowl.

    Science.gov (United States)

    Trefil, Pavel; Bakst, Murray R; Yan, Haifeng; Hejnar, Jiří; Kalina, Jiří; Mucksová, Jitka

    2010-12-01

    Transplantation of male germ line cells into sterilized recipients has been used in mammals for conventional breeding as well as for transgenesis. We have previously adapted this approach for the domestic chicken and we present now an improvement of the germ cell transplantation technique by using an enriched subpopulation of c-Kit-positive spermatogonia as donor cells. Dispersed c-Kit positive testicular cells from 16 to 17 week-old pubertal donors were transplanted by injection directly into the testes of recipient males sterilized by repeated gamma irradiation. We describe the repopulation of the recipient's testes with c-Kit positive donor testicular cells, which resulted in the production of functional heterologous spermatozoa. Using manual semen collection, the first sperm production in the recipient males was observed about nine weeks after the transplantation. The full reproduction cycle was accomplished by artificial insemination of hens and hatching of chickens.

  16. Allogeneic and autologous mode of stem cell transplantation in regenerative medicine: which way to go?

    Science.gov (United States)

    Mamidi, Murali Krishna; Dutta, Susmita; Bhonde, Ramesh; Das, Anjan Kumar; Pal, Rajarshi

    2014-12-01

    Stem cell transplantation is a generic term covering different techniques. However there is argument over the pros and cons of autologous and allogeneic transplants of mesenchymal stem cells (MSCs) for regenerative therapy. Given that the MSCs have already been proven to be safe in patients, we hypothesize that allogeneic transplantation could be more effective and cost-effective as compared to autologous transplantation specifically in older subjects who are the likely victims of degenerative diseases. This analysis is based on the scientific logic that allogeneic stem cells extracted in large numbers from young and healthy donors could be physiologically, metabolically and genetically more stable. Therefore stem cells from young donors may be expected to exhibit higher vigor in secreting trophic factors leading to activation of host tissue-specific stem cells and also be more efficient in remodeling the micro-environmental niche of damaged tissue.

  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. Olfactory ensheathing cell transplantation improves sympathetic skin responses in chronic spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    Zuncheng Zheng; Guifeng Liu; Yuexia Chen; Shugang Wei

    2013-01-01

    Forty-three patients with chronic spinal cord injury for over 6 months were transplanted with bryonic olfactory ensheathing cells, 2-4 × 106, into multiple sites in the injured area under the sur-gical microscope. The sympathetic skin response in patients was measured with an electromyo-graphy/evoked potential instrument 1 day before transplantation and 3-8 weeks after trans-tion. Spinal nerve function of patients was assessed using the American Spinal Injury Association impairment scale. The sympathetic skin response was elicited in 32 cases before olfactory en-sheathing celltransplantation, while it was observed in 34 cases after transplantation. tantly, sympathetic skin response latency decreased significantly and amplitude increased cantly after transplantation. Transplantation of olfactory ensheathing cells also improved American Spinal Injury Association scores for movement, pain and light touch. Our findings indicate that factory ensheathing celltransplantation improves motor, sensory and autonomic nerve functions in patients with chronic spinal cord injury.

  19. Neural stem cell transplantation with Nogo-66 receptor gene silencing to treat severe traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    Dong Wang; Jianjun Zhang; Jingjian Ma; Yuan Mu; Yinghui Zhuang

    2011-01-01

    Inhibition of neurite growth, which is mediated by the Nogo-66 receptor (NgR), affects nerve regeneration following neural stem cell (NSC) transplantation. The present study utilized RNA interference to silence NgR gene expression in NSCs, which were subsequently transplanted into rats with traumatic brain injury. Following transplantation of NSCs transfected with small interfering RNA,typical neural cell-like morphology was detected in injured brain tissues, and was accompanied by absence of brain tissue cavity, increased growth-associated protein 43 mRNA and protein expression,and improved neurological function compared with NSC transplantation alone. Results demonstrated that NSC transplantation with silenced NgR gene promoted functional recovery following brain injury.

  20. Gene expression changes in the injured spinal cord following transplantation of mesenchymal stem cells or olfactory ensheathing cells.

    Directory of Open Access Journals (Sweden)

    Abel Torres-Espín

    Full Text Available Transplantation of bone marrow derived mesenchymal stromal cells (MSC or olfactory ensheathing cells (OEC have demonstrated beneficial effects after spinal cord injury (SCI, providing tissue protection and improving the functional recovery. However, the changes induced by these cells after their transplantation into the injured spinal cord remain largely unknown. We analyzed the changes in the spinal cord transcriptome after a contusion injury and MSC or OEC transplantation. The cells were injected immediately or 7 days after the injury. The mRNA of the spinal cord injured segment was extracted and analyzed by microarray at 2 and 7 days after cell grafting. The gene profiles were analyzed by clustering and functional enrichment analysis based on the Gene Ontology database. We found that both MSC and OEC transplanted acutely after injury induce an early up-regulation of genes related to tissue protection and regeneration. In contrast, cells transplanted at 7 days after injury down-regulate genes related to tissue regeneration. The most important change after MSC or OEC transplant was a marked increase in expression of genes associated with foreign body response and adaptive immune response. These data suggest a regulatory effect of MSC and OEC transplantation after SCI regarding tissue repair processes, but a fast rejection response to the grafted cells. Our results provide an initial step to determine the mechanisms of action and to optimize cell therapy for SCI.

  1. Repeated Gene Transfection Impairs the Engraftment of Transplanted Porcine Neonatal Pancreatic Cells

    Directory of Open Access Journals (Sweden)

    Min Koo Seo

    2011-02-01

    Full Text Available BackgroundPreviously, we reported that neonatal porcine pancreatic cells transfected with hepatocyte growth factor (HGF gene in an Epstein-Barr virus (EBV-based plasmid (pEBVHGF showed improved proliferation and differentiation compared to those of the control. In this study, we examined if pancreatic cells transfected repeatedly with pEBVHGF can be successfully grafted to control blood glucose in a diabetes mouse model.MethodsNeonatal porcine pancreatic cells were cultured as a monolayer and were transfected with pEBVHGF every other day for a total of three transfections. The transfected pancreatic cells were re-aggregated and transplanted into kidney capsules of diabetic nude mice or normal nude mice. Blood glucose level and body weight were measured every other day after transplantation. The engraftment of the transplanted cells and differentiation into beta cells were assessed using immunohistochemistry.ResultsRe-aggregation of the pancreatic cells before transplantation improved engraftment of the cells and facilitated neovascularization of the graft. Right before transplantation, pancreatic cells that were transfected with pEBVHGF and then re-aggregated showed ductal cell marker expression. However, ductal cells disappeared and the cells underwent fibrosis in a diabetes mouse model two to five weeks after transplantation; these mice also did not show controlled blood glucose levels. Furthermore, pancreatic cells transplanted into nude mice with normal blood glucose showed poor graft survival regardless of the type of transfected plasmid (pCEP4, pHGF, or pEBVHGF.ConclusionFor clinical application of transfected neonatal porcine pancreatic cells, further studies are required to develop methods of overcoming the damage for the cells caused by repeated transfection and to re-aggregate them into islet-like structures.

  2. Intrahepatic transplantation of hepatic oval cells for fulminant hepatic failure in rats

    Institute of Scientific and Technical Information of China (English)

    Chen-Xuan Wu; Qi Zou; Zheng-Yan Zhu; Ying-Tang Gao; Yi-Jun Wang

    2009-01-01

    AIM:To evaluate the effect of intrahepatic transplantation of hepatic oval cells (HOC) on fulminant hepatic failure (FHF) in rats. METHODS:HOC obtained from rats were labeled wi th green fluocescent protein (GFP) or 5, 6- carboxyfluorescein diacetate succinmidyl ester (CFDASE). Cell fluorescence was observed under fluorescent microscope at 6, 24, 48 and 72 h after labeling. CFDASE labeled HOC (5 × 106 cells each rat) were injected into livers of rats with FHF induced by D-galactosamine. Serum albumin (ALB), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBil) levels were measured at different time points. Liver function of rats was examined on days 3, 7, 14 and 21 after HOC transplantation. RESULTS:The positive rate of GFP and CFDA-SE labeled HOC was 10% and 90%, respectively, with no significant change in cell viabilities. The survival rate was higher in HOC transplantation group than in control group, especially 48 (9/15 vs 6/15) and 72 h (9/15 vs 4/15) after HOC transplantation. The serum ALT, AST and TBil levels were decreased while the serum Alb level was increased after HOC transplantation. Fluorescence became faded and diffused in liver tissues, suggesting that proliferation and differentiation occur in transplanted HOC. CONCLUSION:CFDA-SE is superior to GFP in labeling HOC, although fluorescence intensity is decreased progressively with cell division. HOC transplantation can improve the liver function and increase the survival rate of recipients.

  3. In vivo generation of transplantable human hematopoietic cells from induced pluripotent stem cells.

    Science.gov (United States)

    Amabile, Giovanni; Welner, Robert S; Nombela-Arrieta, Cesar; D'Alise, Anna Morena; Di Ruscio, Annalisa; Ebralidze, Alexander K; Kraytsberg, Yevgenya; Ye, Min; Kocher, Olivier; Neuberg, Donna S; Khrapko, Konstantin; Silberstein, Leslie E; Tenen, Daniel G

    2013-02-21

    Lineage-restricted cells can be reprogrammed to a pluripotent state known as induced pluripotent stem (iPS) cells through overexpression of 4 transcription factors. iPS cells are similar to human embryonic stem (hES) cells and have the same ability to generate all the cells of the human body, including blood cells. However, this process is extremely inefficient and to date has been unsuccessful at differentiating iPS into hematopoietic stem cells (HSCs). We hypothesized that iPS cells, injected into NOD.Cg-Prkdc(scid) Il2rg(tm1Wjl)/SzJ immunocompromised (NSG) mice could give rise to hematopoietic stem/progenitor cells (HSPCs) during teratoma formation. Here, we report a novel in vivo system in which human iPS cells differentiate within teratomas to derive functional myeloid and lymphoid cells. Similarly, HSPCs can be isolated from teratoma parenchyma and reconstitute a human immune system when transplanted into immunodeficient mice. Our data provide evidence that in vivo generation of patient customized cells is feasible, providing materials that could be useful for transplantation, human antibody generation, and drug screening applications.

  4. Allogeneic stem cell transplantation for advanced acute promyelocytic leukemia in the ATRA and ATO era.

    Science.gov (United States)

    Ramadan, Safaa M; Di Veroli, Ambra; Camboni, Agnese; Breccia, Massimo; Iori, Anna Paola; Aversa, Franco; Cupelli, Luca; Papayannidis, Cristina; Bacigalupo, Andrea; Arcese, William; Lo-Coco, Francesco

    2012-11-01

    The role of allogeneic stem cell transplant in advanced acute promyelocytic leukemia patients who received standard first- and second-line therapy is still unknown. We report the outcome of 31 acute promyelocytic leukemia patients (median age 39 years) who underwent allogeneic transplant in second remission (n=15) or beyond (n=16). Sixteen patients were real-time polymerase chain reaction positive and 15 negative for PML/RARA pre-transplant. The 4-year overall survival was 62% and 31% for patients transplanted in second remission and beyond, respectively (P=0.05), and 64% and 27% for patients with pre-transplant negative and positive real-time polymerase chain reaction, respectively (P=0.03). The 4-year cumulative incidence of relapse was 32% and 44% for patients transplanted in second remission and beyond, respectively (P=0.37), and 30% and 47% for patients transplanted with negative and positive real-time polymerase chain reaction, respectively (P=0.30). Transplant-related mortality was 19.6%. In conclusion, allogeneic transplant is effective in advanced acute promyelocytic leukemia in the all-trans-retinoic acid and arsenic trioxide era, and should be considered once relapse is diagnosed.

  5. Islet cell transplantation for the treatment of type 1 diabetes: recent advances and future challenges

    Directory of Open Access Journals (Sweden)

    Bruni A

    2014-06-01

    Full Text Available Anthony Bruni, Boris Gala-Lopez, Andrew R Pepper, Nasser S Abualhassan, AM James Shapiro Clinical Islet Transplant Program and Department of Surgery, University of Alberta, Edmonton, AB, Canada Abstract: Islet transplantation is a well-established therapeutic treatment for a subset of patients with complicated type I diabetes mellitus. Prior to the Edmonton Protocol, only 9% of the 267 islet transplant recipients since 1999 were insulin independent for >1 year. In 2000, the Edmonton group reported the achievement of insulin independence in seven consecutive patients, which in a collaborative team effort propagated expansion of clinical islet transplantation centers worldwide in an effort to ameliorate the consequences of this disease. To date, clinical islet transplantation has established improved success with insulin independence rates up to 5 years post-transplant with minimal complications. In spite of marked clinical success, donor availability and selection, engraftment, and side effects of immunosuppression remain as existing obstacles to be addressed to further improve this therapy. Clinical trials to improve engraftment, the availability of insulin-producing cell sources, as well as alternative transplant sites are currently under investigation to expand treatment. With ongoing experimental and clinical studies, islet transplantation continues to be an exciting and attractive therapy to treat type I diabetes mellitus with the prospect of shifting from a treatment for some to a cure for all. Keywords: islet transplantation, type I diabetes mellitus, Edmonton Protocol, engraftment, immunosuppression

  6. Cell proliferation markers in the transplanted canine transmissible venereal tumor

    Directory of Open Access Journals (Sweden)

    F.G.A. Santos

    2011-12-01

    Full Text Available Adult male mongrel dogs were subcutaneously transplanted with the canine transmissible venereal tumor (TVT on the hypogastric region. Twelve specimens of tumors were collected, half during the proliferative phase and the other half during the regressive phase. Fragments of the tumor were fixed in 10% buffered formalin and routinely processed for light microscopy. Sections of 4µm were stained by Schorr or AgNOR or either immunostained for MIB1 (Ki67. Schorr stain, AgNOR and MIB1 showed an increased proliferative activity through mitotic index, nuclear argyrophilic protein stain and cycling tumoral cells in the growing tumors, respectively. All of the three cell proliferation markers were able to distinguish the TVT in both evolution phases. MIB1 monoclonal antibody was the best in the morphologic evaluation of growth and regression of TVT. This resulted in higher values than AgNORs counting and mitotic index. MIB1 immunostaining was the most effective parameter of the proliferative activity of TVT. However, a significant correlation has been detected only between mitosis counting and AgNORs.

  7. Delivery of differentiation factors by mesoporous silica particles assists advanced differentiation of transplanted murine embryonic stem cells

    DEFF Research Database (Denmark)

    Garcia-Bennett, Alfonso E; Kozhevnikova, Mariya; König, Niclas;

    2013-01-01

    Stem cell transplantation holds great hope for the replacement of damaged cells in the nervous system. However, poor long-term survival after transplantation and insufficiently robust differentiation of stem cells into specialized cell types in vivo remain major obstacles for clinical application...... neurotrophic factor and glial cell line-derived neurotrophic factor, respectively, with these particles enabled not only robust functional differentiation of motor neurons from transplanted embryonic stem cells but also their long-term survival in vivo. We propose that the delivery of growth factors...... by mesoporous nanoparticles is a potentially versatile and widely applicable strategy for efficient differentiation and functional integration of stem cell derivatives upon transplantation....

  8. Imaging evaluation of pulmonary and abdominal complications following hematopoietic stem cell transplantation.

    Science.gov (United States)

    Coy, David L; Ormazabal, Amaya; Godwin, J David; Lalani, Tasneem

    2005-01-01

    Hematopoietic stem cell transplantation is used to treat hematologic disorders and as an adjunct treatment for solid organ malignancies. After undergoing transplantation, patients are at risk for opportunistic infections and other complications caused by dysfunction of the immune system. Pulmonary complications include cryptogenic organizing pneumonia, opportunistic pneumonias caused by Aspergillus and Zygomycetes species and cytomegalovirus, alveolar hemorrhage, and constrictive bronchiolitis. Abdominal complications include hepatic veno-occlusive disease, graft-versus-host disease (GVHD), colitis, and hemorrhagic cystitis. Allogeneic transplant recipients are at risk for developing GVHD. Autologous and syngeneic transplant recipients are less likely to have chronic or late posttransplantation complications. Nonmyeloablative transplant recipients are less likely to develop opportunistic infections and other complications in the period immediately following transplantation, but are at risk for developing chronic GVHD and other chronic complications. Radiologic evaluation serves as the cornerstone for timely diagnosis of these complications, which is essential to reduce patient morbidity and mortality. Combining clinical factors-including the type of transplant and the point of time during the posttransplantation course-with characteristic imaging features yields the most specific and accurate differential diagnosis for radiologic findings in stem cell transplant recipients.

  9. Transplantation of autologous noncultured epidermal cell suspension in treatment of patients with stable vitiligo

    Institute of Scientific and Technical Information of China (English)

    XU Ai-e; WEI Xiao-dong; CHENG Dong-qing; ZHOU He-fen; QIAN Guo-pei

    2005-01-01

    @@ Treatment of vitiligo by transplantation of noncultured melanocytes containing keratino-cytes has been successful since 1992,1 We report the encouraging results of autologous epidermal cell suspension in the treatment of 24 patients with stable vitiligo since 1998.

  10. Busulfan,cyclophosphamide and etoposide as conditioning for autologous stem cell transplantation in multiple myeloma

    Institute of Scientific and Technical Information of China (English)

    张春阳

    2013-01-01

    Objective To evaluate the efficacy and safety of dose-reduced intravenous busulfan,cyclophosphamide and etoposide(BCV)as conditioning for autologous stem cell transplantation(ASCT)in multiple myeloma(MM)

  11. Allogeneic hematopoietic stem cell transplantation for chronic myelomonocytic leukemia:a report of 12 patients

    Institute of Scientific and Technical Information of China (English)

    孙于谦

    2013-01-01

    Objective To retrospectively review the efficacy of allogeneic hematopoietic stem cell transplantation(allo-HSCT)for chronic myelomonocytic leukemia(CMML).Methods The engraftment,graft versus host disease(GVHD)

  12. Myositis in Griscelli syndrome type 2 treated with hematopoietic cell transplantation

    DEFF Research Database (Denmark)

    Born, Alfred Peter; Müller, Klaus; Marquart, Hanne Vibeke;

    2010-01-01

    and elevated plasma creatine kinase. Muscle biopsy showed massive inflammatory changes in some fascicles, while other fascicles were relatively spared. Clinical symptoms and biopsy changes resolved after immunosuppression and allogeneic hematopoietic cell transplantation. Our results suggest that muscle...

  13. Schwann Cells Transplantation Promoted and the Repair of Brain Stem Injury in Rats

    Institute of Scientific and Technical Information of China (English)

    HONG WAN; YI-HUA AN; MEI-ZHEN SUN; YA-ZHUO ZHANG; ZHONG-CHENG WANG

    2003-01-01

    To explore the possibility of Schwann cells transplantation to promote the repair of injured brain stem reticular structure in rats. Methods Schwann cells originated from sciatic nerves of 1 to 2-day-old rats were expanded and labelled by BrdU in vitro, transplanted into rat brain stem reticular structure that was pre-injured by electric needle stimulus. Immunohistochemistry and myelin-staining were used to investigate the expression of BrdU, GAP-43 and new myelination respectively. Results BrdU positive cells could be identified for up to 8 months and their number increased by about 23%, which mainly migrated toward injured ipsilateral cortex. The GAP-43expression reached its peak in 1 month after transplantation and was significantly higher than that in the control group. New myelination could be seen in destructed brain stem areas. Conclusion The transplantation of Schwann cells can promote the restoration of injured brain stem reticular structure.

  14. 76 FR 11491 - Advisory Council on Blood Stem Cell Transplantation; Request for Nominations for Voting Members

    Science.gov (United States)

    2011-03-02

    ... HUMAN SERVICES Health Resources and Services Administration Advisory Council on Blood Stem Cell Transplantation; Request for Nominations for Voting Members AGENCY: Health Resources and Services Administration (HRSA), HHS. ACTION: Notice. SUMMARY: The Health Resources and Services Administration (HRSA)...

  15. 76 FR 19101 - Advisory Council on Blood Stem Cell Transplantation; Notice of Meeting

    Science.gov (United States)

    2011-04-06

    .... Bill Young Cell Transplantation Program (Program) and the National Cord Blood Inventory (NCBI) Program...; National Marrow Donor Program (NMDP) Analysis of National Cord Blood Inventory (NCBI) and Non-NCBI...

  16. Oral features and dental health in Hurler Syndrome following hematopoietic stem cell transplantation.

    LENUS (Irish Health Repository)

    McGovern, Eleanor

    2010-09-01

    Hurler Syndrome is associated with a deficiency of a specific lysosomal enzyme involved in the degradation of glycosaminoglycans. Hematopoietic stem cell transplantation (HSCT) in early infancy is undertaken to help prevent the accumulation of glycosaminoglycans and improve organ function.

  17. Infection Rates among Acute Leukemia Patients Receiving Alternative Donor Hematopoietic Cell Transplantation

    NARCIS (Netherlands)

    Ballen, Karen; Woo Ahn, Kwang; Chen, Min; Abdel-Azim, Hisham; Ahmed, Ibrahim; Aljurf, Mahmoud; Antin, Joseph; Bhatt, Ami S; Boeckh, Michael; Chen, George; Dandoy, Christopher; George, Biju; Laughlin, Mary J; Lazarus, Hillard M; MacMillan, Margaret L; Margolis, David A; Marks, David I; Norkin, Maxim; Rosenthal, Joseph; Saad, Ayman; Savani, Bipin; Schouten, Harry C; Storek, Jan; Szabolcs, Paul; Ustun, Celalettin; Verneris, Michael R; Waller, Edmund K; Weisdorf, Daniel J; Williams, Kirsten M; Wingard, John R; Wirk, Baldeep; Wolfs, Tom; Young, Jo-Anne H; Auletta, Jeffrey; Komanduri, Krishna V; Lindemans, Caroline; Riches, Marcie L

    2016-01-01

    Alternative graft sources (umbilical cord blood [UCB], matched unrelated donors [MUD], or mismatched unrelated donors [MMUD]) enable patients without a matched sibling donor to receive potentially curative hematopoietic cell transplantation (HCT). Retrospective studies demonstrate comparable outcome

  18. 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...

  19. Brain, Behavior, and Immunity: Biobehavioral influences on recovery following hematopoietic stem cell transplantation

    Science.gov (United States)

    Review of hematopoietic stem cell transplantation and its potential “window of opportunity” during which interventions targeting stress-related behavioral factors can influence the survival, health, and well-being of recipients.

  20. Donor-Derived Smoldering Multiple Myeloma following a Hematopoietic Cell Transplantation for AML

    Science.gov (United States)

    Fiala, Mark; Slade, Michael; Westervelt, Peter

    2017-01-01

    Posttransplant Lymphoproliferative Disorder (PTLD) is one of the most common malignancies complicating solid organ transplantation. In contrast, PTLD accounts for a minority of secondary cancers following allogeneic hematopoietic cell transplantation (HCT). Here we report on a 61-year-old woman who received an ABO-mismatched, HLA-matched unrelated donor hematopoietic cell transplantation from a presumably healthy donor for a diagnosis of acute myeloid leukemia (AML). Eighteen months following her transplant, she developed a monoclonal gammopathy. Bone marrow studies revealed 10% plasma cells, but the patient lacked clinical defining features of multiple myeloma (MM); thus a diagnosis of smoldering multiple myeloma (SMM) was established. Cytogenetic and molecular studies of the bone marrow confirmed the plasma cells were donor-derived. The donor lacks a diagnosis of monoclonal gammopathy of undetermined significance, SMM, or MM. PMID:28316846

  1. Donor-Derived Smoldering Multiple Myeloma following a Hematopoietic Cell Transplantation for AML

    Directory of Open Access Journals (Sweden)

    Bita Fakhri

    2017-01-01

    Full Text Available Posttransplant Lymphoproliferative Disorder (PTLD is one of the most common malignancies complicating solid organ transplantation. In contrast, PTLD accounts for a minority of secondary cancers following allogeneic hematopoietic cell transplantation (HCT. Here we report on a 61-year-old woman who received an ABO-mismatched, HLA-matched unrelated donor hematopoietic cell transplantation from a presumably healthy donor for a diagnosis of acute myeloid leukemia (AML. Eighteen months following her transplant, she developed a monoclonal gammopathy. Bone marrow studies revealed 10% plasma cells, but the patient lacked clinical defining features of multiple myeloma (MM; thus a diagnosis of smoldering multiple myeloma (SMM was established. Cytogenetic and molecular studies of the bone marrow confirmed the plasma cells were donor-derived. The donor lacks a diagnosis of monoclonal gammopathy of undetermined significance, SMM, or MM.

  2. Synthetic Polymer Scaffolds for Stem Cell Transplantation in Retinal Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Michael J. Young

    2011-05-01

    Full Text Available Age-related macular degeneration and retinitis pigmentosa are two leading causes of irreversible blindness characterized by photoreceptor loss. Cell transplantation may be one of the most promising approaches of retinal repair. However, several problems hinder the success of retinal regeneration, including cell delivery and survival, limited cell integration and incomplete cell differentiation. Recent studies show that polymer scaffolds can address these three problems. This article reviews the current literature on synthetic polymer scaffolds used for stem cell transplantation, especially retinal progenitor cells. The advantages and disadvantages of different polymer scaffolds, the role of different surface modifications on cell attachment and differentiation, and controlled drug delivery are discussed. The development of material and surface modification techniques is vital in making cell transplantation a clinical success.

  3. Indications and Results of HLA-Identical Sibling Hematopoietic Cell Transplantation for Sickle Cell Disease.

    Science.gov (United States)

    Walters, Mark C; De Castro, Laura M; Sullivan, Keith M; Krishnamurti, Lakshmanan; Kamani, Naynesh; Bredeson, Christopher; Neuberg, Donna; Hassell, Kathryn L; Farnia, Stephanie; Campbell, Andrew; Petersdorf, Effie

    2016-02-01

    Although a number of published trials exist of HLA-identical sibling hematopoietic cell transplantation (HCT) for sickle cell disease (SCD) that span 2 decades, when and for whom this therapy should be pursued is a subject of debate. Assessments of the risks of transplant-related complications that include infertility and debilitating graft-versus-host disease and long-term quality of life after successful HCT are difficult to perform without prospective trials in transplant and nontransplant cohorts. However, it is possible to assess the risk of mortality and to compare published rates of survival in individuals with SCD treated and not treated by HCT. In this brief review, projections about mortality risk based on recent published reports are reviewed and summarized. The published data show overall survival and event-free survival rates of 95% and 92%, respectively, in children treated by HLA-identical sibling HCT. The overall survival rates in the Center for International Blood and Marrow Transplant Research (N = 412) and European Blood and Marrow Transplant (N = 487) registries were 91% and 95%, respectively. These results provide broad support for the therapeutic value of HLA-identical sibling HCT for children with SCD and serve as the basis for a strong recommendation in favor of the option of HCT when a suitable donor is available. The experience of HLA-identical sibling HCT in adults with SCD is limited but appears to be similar to results in children. These preliminary observations, however, warrant further investigation.

  4. Delayed immune recovery following sequential orthotopic liver transplantation and haploidentical stem cell transplantation in erythropoietic protoporphyria

    NARCIS (Netherlands)

    Smiers, Frans J.; Van de Vijver, Els; Delsing, Bas J. P.; Lankester, Arjan C.; Ball, Lynne M.; Rings, Edmund H. H. M.; van Rheenen, Patrick F.; Bredius, Robbert G. M.

    2010-01-01

    A nine-yr-old boy with EPP suffered from severe skin burns and liver failure caused by progressive cholestasis and fibrosis. OLT was performed without major complications. Four months following liver transplantation he underwent parental haploidentical HSCT. The myeloablative conditioning regimen wa

  5. Verification of cell viability in bioengineered tissues and organs before clinical transplantation.

    Science.gov (United States)

    Jungebluth, Philipp; Haag, Johannes C; Lim, Mei L; Lemon, Greg; Sjöqvist, Sebastian; Gustafsson, Ylva; Ajalloueian, Fatemeh; Gilevich, Irina; Simonson, Oscar E; Grinnemo, Karl H; Corbascio, Matthias; Baiguera, Silvia; Del Gaudio, Costantino; Strömblad, Staffan; Macchiarini, Paolo

    2013-05-01

    The clinical outcome of transplantations of bioartificial tissues and organs depends on the presence of living cells. There are still no standard operative protocols that are simple, fast and reliable for confirming the presence of viable cells on bioartificial scaffolds prior to transplantation. By using mathematical modeling, we have developed a colorimetric-based system (colorimetric scale bar) to predict the cell viability and density for sufficient surface coverage. First, we refined a method which can provide information about cell viability and numbers in an in vitro setting: i) immunohistological staining by Phalloidin/DAPI and ii) a modified colorimetric cell viability assay. These laboratory-based methods and the developed colorimetric-based system were then validated in rat transplantation studies of unseeded and seeded tracheal grafts. This was done to provide critical information on whether the graft would be suitable for transplantation or if additional cell seeding was necessary. The potential clinical impact of the colorimetric scale bar was confirmed using patient samples. In conclusion, we have developed a robust, fast and reproducible colorimetric tool that can verify and warrant viability and integrity of an engineered tissue/organ prior to transplantation. This should facilitate a successful transplantation outcome and ensure patient safety.

  6. MHC Universal Cells Survive in an Allogeneic Environment after Incompatible Transplantation

    Directory of Open Access Journals (Sweden)

    Constança Figueiredo

    2013-01-01

    Full Text Available Cell, tissue, and organ transplants are commonly performed for the treatment of different diseases. However, major histocompatibility complex (MHC diversity often prevents complete donor-recipient matching, resulting in graft rejection. This study evaluates in a preclinical model the capacity of MHC class I-silenced cells to engraft and grow upon allogeneic transplantation. Short hairpin RNA targeting β2-microglobulin (RN_shβ2m was delivered into fibroblasts derived from LEW/Ztm (RT1l (RT1-Al rats using a lentiviral-based vector. MHC class I (RT1-A- expressing and -silenced cells were injected subcutaneously in LEW rats (RT1l and MHC-congenic LEW.1W rats (RT1u, respectively. Cell engraftment and the status of the immune response were monitored for eight weeks after transplantation. In contrast to RT1-A-expressing cells, RT1-A-silenced fibroblasts became engrafted and were still detectable eight weeks after allogeneic transplantation. Plasma levels of proinflammatory cytokines IL-1α, IL-1β, IL-6, TNF-α, and IFN-γ were significantly higher in animals transplanted with RT1-A-expressing cells than in those receiving RT1-A-silenced cells. Furthermore, alloantigen-specific T-cell proliferation rates derived from rats receiving RT1-A-expressing cells were higher than those in rats transplanted with RT1-A-silenced cells. These data suggest that silencing MHC class I expression might overcome the histocompatibility barrier, potentially opening up new avenues in the field of cell transplantation and regenerative medicine.

  7. MHC Universal Cells Survive in an Allogeneic Environment after Incompatible Transplantation

    Science.gov (United States)

    Figueiredo, Constança; Wedekind, Dirk; Müller, Thomas; Vahlsing, Stefanie; Horn, Peter A.; Seltsam, Axel; Blasczyk, Rainer

    2013-01-01

    Cell, tissue, and organ transplants are commonly performed for the treatment of different diseases. However, major histocompatibility complex (MHC) diversity often prevents complete donor-recipient matching, resulting in graft rejection. This study evaluates in a preclinical model the capacity of MHC class I-silenced cells to engraft and grow upon allogeneic transplantation. Short hairpin RNA targeting β2-microglobulin (RN_shβ2m) was delivered into fibroblasts derived from LEW/Ztm (RT1l) (RT1-Al) rats using a lentiviral-based vector. MHC class I (RT1-A-) expressing and -silenced cells were injected subcutaneously in LEW rats (RT1l) and MHC-congenic LEW.1W rats (RT1u), respectively. Cell engraftment and the status of the immune response were monitored for eight weeks after transplantation. In contrast to RT1-A-expressing cells, RT1-A-silenced fibroblasts became engrafted and were still detectable eight weeks after allogeneic transplantation. Plasma levels of proinflammatory cytokines IL-1α, IL-1β, IL-6, TNF-α, and IFN-γ were significantly higher in animals transplanted with RT1-A-expressing cells than in those receiving RT1-A-silenced cells. Furthermore, alloantigen-specific T-cell proliferation rates derived from rats receiving RT1-A-expressing cells were higher than those in rats transplanted with RT1-A-silenced cells. These data suggest that silencing MHC class I expression might overcome the histocompatibility barrier, potentially opening up new avenues in the field of cell transplantation and regenerative medicine. PMID:24350288

  8. Neuronal differentiation of adipose-derived stem cells and their transplantation for cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Guoping Tian; Xiaoguang Luo; Jin Zhou; Jinge Wang; Bing Xu; Li Li; Feng Zhu; Jian Han; Jianping Li; Siyang Zhang

    2012-01-01

    OBJECTIVE: To review published data on the biological characteristics, differentiation and applications of adipose-derived stem cells in ischemic diseases.DATA RETRIEVAL: A computer-based online search of reports published from January 2005 to June 2012 related to the development of adipose-derived stem cells and their transplantation for treatment of cerebral ischemia was performed in Web of Science using the key words"adipose-derived stem cells", "neural-like cells", "transplantation", "stroke", and "cerebral ischemia". SELECTION CRITERIA: The documents associated with the development of adipose-derived stem cells and their transplantation for treatment of cerebral ischemia were selected, and those published in the last 3-5 years or in authoritative journals were preferred in the same field. Totally 89 articles were obtained in the initial retrieval, of which 53 were chosen based on the inclusion criteria. MAIN OUTCOME MEASURES: Biological characteristics and induced differentiation ofadipose-derived stem cells and cell transplantation for disease treatment as well as the underlying mechanism of clinical application. RESULTS: The advantages of adipose-derived stem cells include their ease of procurement, wide availability, rapid expansion, low tumorigenesis, low immunogenicity, and absence of ethical constraints. Preclinical experiments have demonstrated that transplanted adipose-derived stem cells can improve neurological functions, reduce small regions of cerebral infarction, promote angiogenesis, and express neuron-specific markers. The improvement of neurological functions was demonstrated in experiments using different methods and time courses of adipose-derived stem cell transplantation, but the mechanisms remain unclear.CONCLUSION: Further research into the treatment of ischemic disease by adipose-derived stem cell transplantation is needed to determine their mechanism of action.

  9. DI-3-butylphthalide-enhanced hematopoietic stem cell transplantation and endogenous stem cell mobilization for the treatment of cerebral infarcts

    Institute of Scientific and Technical Information of China (English)

    Baoquan Lu; Xiaoming Shang; Yongqiu Li; Hongying Ma; Chunqin Liu; Jianmin Li; Yingqi Zhang; Shaoxin Yao

    2011-01-01

    Exogenous stem cell transplantation and endogenous stem cell mobilization are both effective for the treatment of acute cerebral infarction. The compound dl-3-butylphthalide is known to improve microcirculation and help brain cells at the infarct loci. This experiment aimed to investigate the effects of dl-3-butylphthalide intervention based on the transplantation of hematopoietic stem cells and mobilization of endogenous stem cells in a rat model of cerebral infarction, following middle cerebral artery occlusion. Results showed that neurological function was greatly improved and infarct volume was reduced in rats with cerebral infarction. Data also showed that dl-3-butylphthalide can promote hematopoietic stem cells to transform into vascular endothelial cells and neuronal-like cells, and also enhance the therapeutic effect on cerebral infarction by hematopoietic stem cell transplantation and endogenous stem cell mobilization.

  10. Ex Vivo Expansion or Manipulation of Stem Cells to Improve Outcome of Umbilical Cord Blood Transplantation.

    Science.gov (United States)

    Horwitz, Mitchell E

    2016-02-01

    The outcome of umbilical cord blood transplantation for adult patients with hematologic malignancies now rivals that of matched unrelated donor transplantation. However, delayed hematopoietic and immunologic recovery remains a source of significant morbidity and mortality. Multiple strategies are now being studied to overcome these limitations. One strategy involves ex vivo expansion of the umbilical cord blood unit prior to transplantation. A second strategy involves exposure of the umbilical cord blood graft to compounds aimed at improving homing and engraftment following transplantation. Such a strategy may also address the problem of slow hematopoietic recovery as well as the increased risk of graft failure. Many of these strategies are now being tested in late phase multi-center clinical trials. If proven cost-effective and efficacious, they may alter the landscape of donor options for allogeneic stem cell transplantation.

  11. Mesenchymal Stem Cells in Organ Transplantation: Immunomodulatory properties of mesenchymal stem cells for application in organ transplantation

    NARCIS (Netherlands)

    M.J. Crop (Meindert)

    2010-01-01

    textabstractKidney transplantation is the only effective treatment for patients with end-stage renal disease. Transplantation of a donor organ, however, leads to recognition of the foreign donor antigens by the recipient’s immune system, resulting in rejection of the graft. In addition, ischemia-rep

  12. Nonmyeloablative Allogeneic Stem-Cell Transplantation for Metastatic Renal Cell Cancer: A Review and Update

    Directory of Open Access Journals (Sweden)

    P. Erotocritou

    2006-01-01

    Full Text Available Metastatic renal cell carcinoma (RCC is resistant to conventional chemotherapy and radiotherapy. However, immunotherapy appears to be effective in 15—20% of cases, with interleukin-2 becoming the standard therapy for this disease. As a consequence of the immune susceptibility of RCC, other avenues of immunotherapy are being explored, such as nonmyeloablative allogeneic stem cell transplantation (NST. A number of trials have shown NST to be effective in varying degrees, causing partial or complete regression. Although nonmyeloablative conditioning is safer than myeloablative conditioning, its role has yet to be clearly proven as many studies have shown variable effect. Alongside this limitation, transplant-related toxicity also forms obstacles. Regardless of the limitation of NST, further refinement of the technique, with appropriate patient selection, may lead to this being an effective therapeutic choice for a significant number of individuals.

  13. Amelioration of experimental autoimmune encephalomyelitis through transplantation of placental derived mesenchymal stem cells

    Science.gov (United States)

    Jiang, Hong; Zhang, Yuanyuan; Tian, Kewei; Wang, Beibei; Han, Shu

    2017-01-01

    Placental derived mesenchymal stem cells (PMSCs) have been suggested as a possible source of cells to treat multiple sclerosis (MS) due to their immunomodulatory functions, lack of ethical concerns, and potential to differentiate into neurons and oligodendrocytes. To investigate whether PMSCs share similar characteristics with embryonic mesenchymal stem cells (EMSCs), and if transplanted PMSCs have the ability to integrate and replace degenerated neural cells, we transplanted rat PMSCs and EMSCs into the central nervous system (CNS) of Lewis rats with experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Our findings demonstrated that transplanted PMSCs, similar to EMSCs, were effective in decreasing infiltrating inflammatory cells, preserving axons, and ameliorating demyelination, thereby improving the neurological functions of animals. Moreover, both PMSCs and EMSCs had the ability to migrate into inflamed tissues and express neural–glial lineage markers. These findings suggest that PMSCs may replace EMSCs as a source of cells in MS stem cell therapy. PMID:28186117

  14. 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...... myeloid leukemia. The occurrence of chronic GVHD had a positive impact on overall survival (P = .047). Transplant-related mortality rates were low. Multivariate analysis identified only blast phase at transplantation (hazard ratio 3.68, P = .0011) and unrelated stem cell donor (hazard ratio 2.98, P = .011......) 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....

  15. A problem-solving education intervention in caregivers and patients during allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Bevans, Margaret; Wehrlen, Leslie; Castro, Kathleen; Prince, Patricia; Shelburne, Nonniekaye; Soeken, Karen; Zabora, James; Wallen, Gwenyth R

    2014-05-01

    The aim of this study was to determine the effect of problem-solving education on self-efficacy and distress in informal caregivers of allogeneic hematopoietic stem cell transplantation patients. Patient/caregiver teams attended three 1-hour problem-solving education sessions to help cope with problems during hematopoietic stem cell transplantation. Primary measures included the Cancer Self-Efficacy Scale-transplant and Brief Symptom Inventory-18. Active caregivers reported improvements in self-efficacy (p caregiver responders also reported better health outcomes such as fatigue. The effect of problem-solving education on self-efficacy and distress in hematopoietic stem cell transplantation caregivers supports its inclusion in future interventions to meet the multifaceted needs of this population.

  16. Hormone Use for Therapeutic Amenorrhea and Contraception During Hematopoietic Cell Transplantation.

    Science.gov (United States)

    Chang, Katherine; Merideth, Melissa A; Stratton, Pamela

    2015-10-01

    There is a growing population of women who have or will undergo hematopoietic stem cell transplant for a variety of malignant and benign conditions. Gynecologists play an important role in addressing the gynecologic and reproductive health concerns for these women throughout the transplant process. As women undergo cell transplantation, they should avoid becoming pregnant and are at risk of uterine bleeding. Thus, counseling about and implementing hormonal treatments such as gonadotropin-releasing hormone agonists, combined hormonal contraceptives, and progestin-only methods help to achieve therapeutic amenorrhea and can serve as contraception during the peritransplant period. In this commentary, we summarize the timing, risks, and benefits of the hormonal options just before, during, and for the year after hematopoietic stem cell transplantation.

  17. Transplanted Human Umbilical Cord Mesenchymal Stem Cells Facilitate Lesion Repair in B6.Fas Mice

    Directory of Open Access Journals (Sweden)

    Guang-ping Ruan

    2014-01-01

    Full Text Available Background. Systemic lupus erythematosus (SLE is a multisystem disease that is characterized by the appearance of serum autoantibodies. No effective treatment for SLE currently exists. Methods. We used human umbilical cord mesenchymal stem cell (H-UC-MSC transplantation to treat B6.Fas mice. Results. After four rounds of cell transplantation, we observed a statistically significant decrease in the levels of mouse anti-nuclear, anti-histone, and anti-double-stranded DNA antibodies in transplanted mice compared with controls. The percentage of CD4+CD25+Foxp3+ T cells in mouse peripheral blood significantly increased after H-UC-MSC transplantation. Conclusions. The results showed that H-UC-MSCs could repair lesions in B6.Fas mice such that all of the relevant disease indicators in B6.Fas mice were restored to the levels observed in normal C57BL/6 mice.

  18. Anti-Erythropoietin Antibody Associated Pure Red Cell Aplasia Resolved after Liver Transplantation

    Directory of Open Access Journals (Sweden)

    Annie K. Hung

    2015-01-01

    Full Text Available Patients undergoing antiviral therapy for chronic hepatitis C often develop anemia secondary to ribavirin and interferon. Recombinant erythropoietin has been used to improve anemia associated with antiviral therapy and to minimize dose reductions, which are associated with decreased rates of sustained virologic response. A rare potential side effect of recombinant erythropoietin is anti-erythropoietin antibody associated pure red cell aplasia. In chronic kidney disease patients with this entity, there have been good outcomes associated with renal transplant and subsequent immunosuppression. In this case, a chronic liver disease patient developed anti-erythropoietin associated pure red cell aplasia and recovered after liver transplantation and immunosuppression. It is unclear whether it is the transplanted organ, the subsequent immunosuppression, or the combination that contributed to the response. In conclusion, anti-erythropoietin associated pure red cell aplasia is a serious complication of erythropoietin therapy, but this entity should not be considered a contraindication for solid organ transplantation.

  19. Enhanced infarct myocardium repair mediated by thermosensitive copolymer hydrogel-based stem cell transplantation

    Science.gov (United States)

    Xia, Yu; Zhu, Kai; Lai, Hao; Lang, Meidong; Xiao, Yan; Lian, Sheng

    2015-01-01

    Mesenchymal stem cell (MSC) transplantation by intramyocardial injection has been proposed as a promising therapy strategy for cardiac repair after myocardium infarction. However, low retention and survival of grafted MSCs hinder its further application. In this study, copolymer with N-isopropylacrylamide/acrylic acid/2-hydroxylethyl methacrylate-poly(ɛ-caprolactone) ratio of 88:9.6:2.4 was bioconjugated with type I collagen to construct a novel injectable thermosensitive hydrogel. The injectable and biocompatible hydrogel-mediated MSC transplantation could enhance the grafted cell survival in the myocardium, which contributed to the increased neovascularization, decreased interstitial fibrosis, and ultimately improved heart function to a significantly greater degree than regular MSC transplantation. We suggest that this novel hydrogel has the potential for future stem cell transplantation. PMID:25432986

  20. Enhanced infarct myocardium repair mediated by thermosensitive copolymer hydrogel-based stem cell transplantation.

    Science.gov (United States)

    Xia, Yu; Zhu, Kai; Lai, Hao; Lang, Meidong; Xiao, Yan; Lian, Sheng; Guo, Changfa; Wang, Chunsheng

    2015-05-01

    Mesenchymal stem cell (MSC) transplantation by intramyocardial injection has been proposed as a promising therapy strategy for cardiac repair after myocardium infarction. However, low retention and survival of grafted MSCs hinder its further application. In this study, copolymer with N-isopropylacrylamide/acrylic acid/2-hydroxylethyl methacrylate-poly(ɛ-caprolactone) ratio of 88:9.6:2.4 was bioconjugated with type I collagen to construct a novel injectable thermosensitive hydrogel. The injectable and biocompatible hydrogel-mediated MSC transplantation could enhance the grafted cell survival in the myocardium, which contributed to the increased neovascularization, decreased interstitial fibrosis, and ultimately improved heart function to a significantly greater degree than regular MSC transplantation. We suggest that this novel hydrogel has the potential for future stem cell transplantation.

  1. Haematopoietic stem cell transplantation as first-line treatment in myeloma: a global perspective of current concepts and future possibilities

    Directory of Open Access Journals (Sweden)

    Catriona Elizabeth Mactier

    2012-10-01

    Full Text Available Stem cell transplantation forms an integral part of the treatment for multiple myeloma. This paper reviews the current role of transplantation and the progress that has been made in order to optimize the success of this therapy. Effective induction chemotherapy is important and a combination regimen incorporating the novel agent bortezomib is now favorable. Adequate induction is a crucial adjunct to stem cell transplantation and in some cases may potentially postpone the need for transplant. Different conditioning agents prior to transplantation have been explored: high-dose melphalan is most commonly used and bortezomib is a promising additional agent. There is no well-defined superior transplantation protocol but single or tandem autologous stem cell transplantations are those most commonly used, with allogeneic transplantation only used in clinical trials. The appropriate timing of transplantation in the treatment plan is a matter of debate. Consolidation and maintenance chemotherapies, particularly thalidomide and bortezomib, aim to improve and prolong disease response to transplantation and delay recurrence. Prognostic factors for the outcome of stem cell transplant in myeloma have been highlighted. Despite good responses to chemotherapy and transplantation, the problem of disease recurrence persists. Thus, there is still much room for improvement. Treatments which harness the graft-versus-myeloma effect may offer a potential cure for this disease. Trials of novel agents are underway, including targeted therapies for specific antigens such as vaccines and monoclonal antibodies.

  2. Red cell antibodies arising from solid organ transplants.

    Science.gov (United States)

    Ramsey, G

    1991-01-01

    RBC antibodies arising from transplanted organs and directed against recipient RBCs represent a well-established immunohematologic complication of solid organ transplantation. In ABO-unmatched organs, the frequency and severity of graft antibodies and hemolysis generally increase with the size (lymphoid content) of the organ, from kidney to liver to heart-lung transplants. In the cases reviewed here, the frequency of hemolysis increased in cyclosporine-treated kidney transplant recipients and O-to-A liver transplant recipients and decreased in group AB liver transplant recipients and kidney transplant recipients receiving azathioprine or low-dose postoperative graft irradiation. Available data cannot otherwise distinguish which cyclosporine-treated recipients of ABO-unmatched kidneys and livers (30-40% of total) will develop graft antibody. There has been no conclusive effect to date of the age, race, or gender of the donor or the recipient, of cadaver versus living kidney donors, or of patients' A2 or secretor status. In a few cases of living-donor kidney grafts, the donor was the patient's mother or wife who had been exposed to the recipient's RBC antigens via pregnancy. The ABO antibodies are typically IgG, appear 7 to 10 days after transplantation, and last for about a month. If immediate-spin crossmatching is done routinely, DATs are recommended in compatibility testing after ABO-unmatched transplants. Changes in the immunosuppressive regimen, such as a change from cyclosporine therapy, have not affected the duration of these antibodies. Most patients require only transfusions for this self-limited process, but six cases of hemolysis-induced acute renal failure have been reported, and one death was attributed to complications of hemolysis. RBC or plasma exchange has been performed in a few fulminant cases. RBCs of the donor's blood type are given when antibody appears. Some workers recommend such transfusion as prophylaxis at the time of surgery, although in

  3. Hepatic tissue engineering: from transplantation to customized cell-based liver directed therapies from the laboratory.

    Science.gov (United States)

    Fiegel, Henning C; Kaufmann, Peter M; Bruns, Helge; Kluth, Dietrich; Horch, Raymund E; Vacanti, Joseph P; Kneser, Ulrich

    2008-01-01

    Today, liver transplantation is still the only curative treatment for liver failure due to end-stages liver diseases. Donor organ shortage, high cost and the need of immunosuppressive medications are still the major limitations in the field of liver transplantation. Thus, alternative innovative cell-based liver directed therapies, e.g. liver tissue engineering, are under investigation with the aim, that in future an artificial liver tissue could be created and be used for the replacement of the liver function in patients. Using cells instead of organs in this setting should permit (i) expansion of cells in an in vitro phase, (ii) genetic or immunological manipulation of cells for transplantation, (iii) tissue typing and cryopreservation in a cell bank, and (iv) the ex vivo genetic modification of patient's own cells prior re-implantation. Function and differentiation of liver cells are influenced by the three-dimensional organ architecture. The use of polymeric matrices permits the three dimensional formation of a neo-tissue and specific stimulation by adequate modification of the matrix-surface which might be essential for appropriate differentiation of transplanted cells. Additionally, culturing hepatocytes on three dimensional matrices permits culture in a flow bioreactor system with increased function and survival of the cultured cells. Based on bioreactor technology, bioartificial liver devices (BAL) are developed for extracorporeal liver support. Although BALs improved clinical and metabolic conditions, increased patient survival rates have not been proven yet. For intra-corporeal liver replacement, a concept which combines Tissue Engineering using three-dimensional, highly porous matrices with cell transplantation could be useful. In such a concept, whole liver mass transplantation, long term engraftment and function as well as correction of a metabolic defect in animal models could be achieved with a principally reversible procedure. Future studies have to

  4. CYTOMEGALOVIRUS INTERSTITIAL PNEUMONITIS FOLLOWING ALLOGENEIC PERIPHERAL BLOOD STEM CELL TRANSPLANTATION

    Institute of Scientific and Technical Information of China (English)

    XU Xiao-hua; HUANG Lian-sheng; ZHANG Xiao-hong; ZHU Kang-er; XU Yang; WU Dong; ZHAO Xiao-ying

    2005-01-01

    Objective: To explore the risk factors and prophylaxis and treatment of cytomegalovirus interstitial pneumonitis(CMV-IP) after allogeneic peripheral blood stem cell transplantation (allo-PBSCT). Methods: 43 patients who received allo-PBSCT were allocated to either a Gancyclovir(GCV)-prophylaxis group (n=19) or a non-GCV prophylaxis group (n=24).A comparison was made of the incidence of CMV-IP in patients given or not given prophylactic gancyclovir. Results: 9patients in non-GCV prophylaxis group developed late CMV-IP (P<0.05). Graft-versus-host-disease (GVHD) may be associated with a high risk of CMV-IP. 5 cases of CMV-IP were successfully treated with GCV, but 3 cases died of CMV-IP.The most common adverse event of GCV was neutropenia, but was reversible. Conclusion: CMV infection was a major cause of interstitial pneumonitis after allo-PBSCT, which correlated strongly with the severity of GVHD. Gancyclovir was shown to be effective in both prophylaxis and treatment of CMV-IP.

  5. Noninvasive Assessment of Cell Fate and Biology in Transplanted Mesenchymal Stem Cells.

    Science.gov (United States)

    Franchi, Federico; Rodriguez-Porcel, Martin

    2017-01-01

    Recently, molecular imaging has become a conditio sine qua non for cell-based regenerative medicine. Developments in molecular imaging techniques, such as reporter gene technology, have increasingly enabled the noninvasive assessment of the fate and biology of cells after cardiovascular applications. In this context, bioluminescence imaging is the most commonly used imaging modality in small animal models of preclinical studies. Here, we present a detailed protocol of a reporter gene imaging approach for monitoring the viability and biology of Mesenchymal Stem Cells transplanted in a mouse model of myocardial ischemia reperfusion injury.

  6. Burden of morbidity in 10+ year survivors of hematopoietic cell transplantation: report from the bone marrow transplantation survivor study.

    Science.gov (United States)

    Sun, Can-Lan; Kersey, John H; Francisco, Liton; Armenian, Saro H; Baker, K Scott; Weisdorf, Daniel J; Forman, Stephen J; Bhatia, Smita

    2013-07-01

    Long-term morbidity after hematopoietic cell transplantation (HCT) is unknown. The risk of physical and psychological health in 324 patients who had survived 10 or more years after HCT and a sibling comparison group (n = 309) was evaluated. Using the Common Terminology Criteria for Adverse Events, the 15-year cumulative incidence of severe/life-threatening/fatal conditions was 41% (95% confidence interval, 34% to 48%). HCT survivors were 5.7 times as likely to develop a severe/life-threatening condition (P survivors returned to the transplantation center for their cancer-related care. The burden of long-term physical and emotional morbidity borne by survivors remains substantial, even beyond 10 years after HCT; however, specialized health care is underused. Patients, families, and healthcare providers need to be made aware of the high burden, so they can plan for post-HCT care, even many years after HCT.

  7. Nontuberculous mycobacterial infection in hematopoietic stem cell and solid organ transplant recipients.

    Science.gov (United States)

    Doucette, Karen; Fishman, Jay A

    2004-05-15

    Nontuberculous mycobacteria (NTM) are ubiquitous environmental organisms. In immunocompetent hosts, they are a rare cause of disease. In immunocompromised hosts, disease due to NTM is well documented. Reports of NTM disease have increased in hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients. This increase may reflect increased numbers of transplants, intensification of immune suppressive regimens, prolonged survival of transplant recipients, and/or improved diagnostic techniques. The difficulty of diagnosis and the impact associated with infections due to NTM in HSCT and SOT recipients necessitates that, to ensure prompt diagnosis and early initiation of therapy, a high level of suspicion for NTM disease be maintained. The most common manifestations of NTM infection in SOT recipients include cutaneous and pleuropulmonary disease, and, in HSCT recipients, catheter-related infection. Skin and pulmonary lesions should be biopsied for histologic examination, special staining, and microbiologic cultures, including cultures for bacteria, Nocardia species, fungi, and mycobacteria. Mycobacterial infections associated with catheters may be documented by tunnel or blood (isolator) cultures. Susceptibility testing of mycobacterial isolates is an essential component of optimal care. The frequent isolation of NTM other than Mycobacterium avium complex (MAC) from transplant recipients limits the extrapolation of therapeutic data from human immunodeficiency virus-infected individuals to the population of transplant recipients. Issues involved in the management of NTM disease in transplant recipients are characterized by a case of disseminated infection due to Mycobacterium avium complex in a lung transplant recipient, with a review of the relevant literature.

  8. Delayed olfactory ensheathing cell transplants reduce nociception after dorsal root injury.

    Science.gov (United States)

    Wu, Ann; Lauschke, Jenny L; Gorrie, Catherine A; Cameron, Nicholas; Hayward, Ian; Mackay-Sim, Alan; Waite, Phil M E

    2011-05-01

    Injury to cervical dorsal roots mimics the deafferentation component of brachial plexus injury in humans, with intractable neuropathic pain in the deafferented limb being a common consequence. Such lesions are generally not amenable to surgical repair. The use of olfactory ensheathing cells (OECs) for dorsal root repair, via acute transplantation, has been successful in several studies. From a clinical point of view, delayed transplantation of OECs would provide a more realistic timeframe for repair. In this study we investigated the effect of delayed OEC transplantation on functional recovery of skilled forepaw movements and amelioration of neuropathic pain, using a C7 and C8 dorsal root injury rat model previously established in our lab. We found that OEC transplantation to the dorsal horn 1 week after root injury effectively attenuated neuropathic disturbances associated with dorsal root injury, including spontaneous pain behavior, tactile allodynia and thermal hyperalgesia. The sensory controls of complex, goal-oriented skilled reaching and ladder walking, however, were not improved by delayed OEC transplantation. We did not detect any significant influence of transplanted OECs on injury-induced central reorganisation and afferent sprouting. The anti-nociceptive effect mediated by OEC transplants may therefore be explained by alternative mechanisms such as modification of inflammation and astrogliosis. The significant effect of OEC transplants in mitigating neuropathic pain may be clinically useful in intractable pain syndromes arising from deafferentation. This article is part of a Special Issue entitled: Understanding olfactory ensheathing glia and their prospect for nervous system repair.

  9. Immunizations in solid organ and hematopoeitic stem cell transplant patients: A comprehensive review

    Science.gov (United States)

    L'Huillier, Arnaud G; Kumar, Deepali

    2015-01-01

    The Solid Organ Transplantation (SOT) and Haematopoietic Stem Cell Transplantation (HSCT) population is continuously increasing as a result of broader indications for transplant and improved survival. Infectious diseases, including vaccine-preventable diseases, are a significant threat for this population, primarily after but also prior to transplantation. As a consequence, clinicians must ensure that patients are optimally immunized before transplantation, to provide the best protection during the early post-transplantation period, when immunosuppression is the strongest and vaccine responses are poor. After 3–6 months, inactivated vaccines immunization can be resumed. By contrast, live-attenuated vaccines are lifelong contraindicated in SOT patients, but can be considered in HSCT patients at least 2 years after transplantation, if there is no immunosuppression or graft-versus-host-disease. However, because of the advantages of live-attenuated over inactivated vaccines - and also sometimes the absence of an inactivated alternative - an increasing number of prospective studies on live vaccine immunization after transplantation are performed and give new insights about safety and immunogenicity in this population. PMID:26291740

  10. American Society of Blood and Marrow Transplantation, European Society of Blood and Marrow Transplantation, Blood and Marrow Transplant Clinical Trials Network, and International Myeloma Working Group Consensus Conference on Salvage Hematopoietic Cell Transplantation in Patients with Relapsed Multiple Myeloma

    NARCIS (Netherlands)

    S. Giralt; L. Garderet (Laurent); B.G.M. Durie (Brian); G. Cook (Gordon); G. Gahrton (Gösta); B. Bruno (Benedetto); P. Hari (Paremesweran); H.M. Lokhorst (Henk); P.L. McCarthy (Philip); A. Krishnan (Amrita); P. Sonneveld (Pieter); H. Goldschmidt (Harmut); S. Jagannath (Sundar); B. Barlogie (Bart); M.V. Mateos; P. Gimsing (Peter); O. Sezer; J. Mikhael (Joseph); J. Lu (Jin); M.A. Dimopoulos (Meletios); R.N. Mazumder (Ramendra N.); A. Palumbo (Antonio); R. Abonour (Rafat); K. Anderson (Kenneth); M. Attal (Michel); J. Blade; J. Bird (Jenny); M. Cavo (Michele); R.L. Comenzo; J. de la Rubia (Javier); H. Einsele (Hermann); R. Garcia-Sanz (Ramon); J. Hillengass (Jens); S. Holstein (Sarah); H.E. Johnsen (Hans); D. Joshua; G. Koehne (Guenther); S. Kumar (Shaji); R. Kyle (Robert); X. Leleu; S. Lonial (Sagar); H. Ludwig (Heinz); H. Nahi (Hareth); A. Nooka (Anil); R.Z. Orlowski (Robert); S.V. Rajkumar (Vincent); A. Reiman (Anthony); P.G. Richardson (Paul Gerard); E. Riva (Eloisa); J. San Miguel (Jesús); I. Turreson (Ingemar); S. Usmani (Saad); D. Vesole (David); W. Bensinger; M. Qazilbash (Muzaffer); Y. Efebera (Yvonne); M. Mohty (Mohamad); C. Gasparreto (Christina); J. Gajewski (James); C.F. LeMaistre (Charles F.); C. Bredeson (Chris); P. Moreau; M. Pasquini (Marcelo); N. Kroeger (Nicolaus); E.A. Stadtmauer (Edward)

    2015-01-01

    textabstractIn contrast to the upfront setting in which the role of high-dose therapy with autologous hematopoietic cell transplantation (HCT) as consolidation of a first remission in patients with multiple myeloma (MM) is well established, the role of high-dose therapy with autologous or allogeneic

  11. 12 hours after cerebral ischemia is the optimal time for bone marrow mesenchymal stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Seyed Mojtaba Hosseini

    2015-01-01

    Full Text Available Cell therapy using stem cell transplantation against cerebral ischemia has been reported. However, it remains controversial regarding the optimal time for cell transplantation and the transplantation route. Rat models of cerebral ischemia were established by occlusion of the middle cerebral artery. At 1, 12 hours, 1, 3, 5 and 7 days after cerebral ischemia, bone marrow mesenchymal stem cells were injected via the tail vein. At 28 days after cerebral ischemia, rat neurological function was evaluated using a 6-point grading scale and the pathological change of ischemic cerebral tissue was observed by hematoxylin-eosin staining. Under the fluorescence microscope, the migration of bone marrow mesenchymal stem cells was examined by PKH labeling. Caspase-3 activity was measured using spectrophotometry. The optimal neurological function recovery, lowest degree of ischemic cerebral damage, greatest number of bone marrow mesenchymal stem cells migrating to peri-ischemic area, and lowest caspase-3 activity in the ischemic cerebral tissue were observed in rats that underwent bone marrow mesenchymal stem cell transplantation at 12 hours after cerebral ischemia. These findings suggest that 12 hours after cerebral ischemia is the optimal time for tail vein injection of bone marrow mesenchymal stem cell transplantation against cerebral ischemia, and the strongest neuroprotective effect of this cell therapy appears at this time.

  12. Points regarding cell transplantation for the treatment of spinal cord injur y

    Institute of Scientific and Technical Information of China (English)

    Chizuka Ide; Kenji Kanekiyo

    2016-01-01

    Transplantation of somatic cells, including bone marrow stromal cells (BMSCs), bone marrow mononu-clear cells (BMNCs), and choroid plexus epithelial cells (CPECs), enhances the outgrowth of regenerating axons and promotes locomotor improvements. They are not integrated into the host spinal cord, but disappear within 2-3 weeks after transplantation. Regenerating axons extend at the spinal cord lesion through the astrocyte-devoid area that is iflled with connective tissue matrices. Regenerating axons have characteristics of peripheral nerves:they are associated with Schwann cells, and embedded in connective tissue matrices. It has been suggested that neurotrophic factors secreted from BMSCs and CPECs promote“intrinsic”ability of the spinal cord to regenerate. Transplanted Schwann cells survive long-term, and are integrated into the host spinal cord, serving as an effective scaffold for the outgrowth of regenerating axons in the spinal cord. The disadvantage that axons are blocked to extend through the glial scar at the border of the lesion is overcome. Schwann cells have been approved for clinical applications. Neural stem/progenitor cells (NSPCs) survive long-term, proliferate, and differentiate into glial cells and/or neurons after trans-plantation. No method is available at present to manipulate and control the behaviors of NPSCs to allow them to appropriately integrate into the host spinal cord. NPSP transplantation is not necessarily effective for locomotor improvement.

  13. Successful transplantation of human hepatic stem cells with restricted localization to liver using hyaluronan grafts.

    Science.gov (United States)

    Turner, Rachael A; Wauthier, Eliane; Lozoya, Oswaldo; McClelland, Randall; Bowsher, James E; Barbier, Claire; Prestwich, Glenn; Hsu, Edward; Gerber, David A; Reid, Lola M

    2013-02-01

    Cell therapies are potential alternatives to organ transplantation for liver failure or dysfunction but are compromised by inefficient engraftment, cell dispersal to ectopic sites, and emboli formation. Grafting strategies have been devised for transplantation of human hepatic stem cells (hHpSCs) embedded into a mix of soluble signals and extracellular matrix biomaterials (hyaluronans, type III collagen, laminin) found in stem cell niches. The hHpSCs maintain a stable stem cell phenotype under the graft conditions. The grafts were transplanted into the livers of immunocompromised murine hosts with and without carbon tetrachloride treatment to assess the effects of quiescent versus injured liver conditions. Grafted cells remained localized to the livers, resulting in a larger bolus of engrafted cells in the host livers under quiescent conditions and with potential for more rapid expansion under injured liver conditions. By contrast, transplantation by direct injection or via a vascular route resulted in inefficient engraftment and cell dispersal to ectopic sites. Transplantation by grafting is proposed as a preferred strategy for cell therapies for solid organs such as the liver.

  14. 12 hours after cerebral ischemia is the optimal time for bone marrow mesenchymal stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    Seyed Mojtaba Hosseini; Mohammad Farahmandnia; Zahra Razi; Somayeh Delavarifar; Benafsheh Shakibajahromi

    2015-01-01

    Cell therapy using stem cell transplantation against cerebral ischemia has been reported. However, it remains controversial regarding the optimal time for cell transplantation and the transplantation route. Rat models of cerebral ischemia were established by occlusion of the middle cerebral artery. At 1, 12 hours, 1, 3, 5 and 7 days after cerebral ischemia, bone marrow mesenchymal stem cells were injected via the tail vein. At 28 days after cerebral ischemia, rat neurological function was evaluated using a 6-point grading scale and the pathological change of ischemic cerebral tissue was observed by hematoxylin-eosin staining. Under the lfuorescence microscope, the migration of bone marrow mesenchymal stem cells was examined by PKH labeling. Caspase-3 activity was measured using spectrophotometry. The optimal neurological function recovery, lowest degree of ischemic cerebral damage, greatest number of bone marrow mesenchymal stem cells migrating to peri-ischemic area, and lowest caspase-3 activity in the ischemic cerebral tissue were observed in rats that underwent bone marrow mesenchymal stem cell transplantation at 12 hours after cerebral ischemia. These ifndings suggest that 12 hours after cerebral ischemia is the optimal time for tail vein injection of bone marrow mesenchymal stem cell transplantation against cerebral ischemia, and the strongest neuroprotective effect of this cell therapy appears at this time.

  15. Transplantation of autologous bone marrow-derived mesenchymal stem cells for traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    Jindou Jiang; Xingyao Bu; Meng Liu; Peixun Cheng

    2012-01-01

    Results from the present study demonstrated that transplantation of autologous bone marrow-derived mesenchymal stem cells into the lesion site in rat brain significantly ameliorated brain tissue pathological changes and brain edema, attenuated glial cell proliferation, and increased brain-derived neurotrophic factor expression. In addition, the number of cells double-labeled for 5-bromodeoxyuridine/glial fibrillary acidic protein and cells expressing nestin increased. Finally, blood vessels were newly generated, and the rats exhibited improved motor and cognitive functions. These results suggested that transplantation of autologous bone marrow-derived mesenchymal stem cells promoted brain remodeling and improved neurological functions following traumatic brain injury.

  16. Monitoring of organ transplants through genomic analyses of circulating cell-free DNA

    Science.gov (United States)

    de Vlaminck, Iwijn

    Solid-organ transplantation is the preferred treatment for patients with end-stage organ diseases, but complications due to infection and acute rejection undermine its long-term benefits. While clinicians strive to carefully monitor transplant patients, diagnostic options are currently limited. My colleagues and I in the lab of Stephen Quake have found that a combination of next-generation sequencing with a phenomenon called circulating cell-free DNA enables non-invasive diagnosis of both infection and rejection in transplantation. A substantial amount of small fragments of cell-free DNA circulate in blood that are the debris of dead cells. We discovered that donor specific DNA is released in circulation during injury to the transplant organ and we show that the proportion of donor DNA in plasma is predictive of acute rejection in heart and lung transplantation. We profiled viral and bacterial DNA sequences in plasma of transplant patients and discovered that the relative representation of different viruses and bacteria is informative of immunosuppression. This discovery suggested a novel biological measure of a person's immune strength, a finding that we have more recently confirmed via B-cell repertoire sequencing. Lastly, our studies highlight applications of shotgun sequencing of cell-free DNA in the broad, hypothesis free diagnosis of infection.

  17. Human hepatocyte growth factor (hHGF-modified hepatic oval cells improve liver transplant survival.

    Directory of Open Access Journals (Sweden)

    Zhu Li

    Full Text Available Despite progress in the field of immunosuppression, acute rejection is still a common postoperative complication following liver transplantation. This study aims to investigate the capacity of the human hepatocyte growth factor (hHGF in modifying hepatic oval cells (HOCs administered simultaneously with orthotopic liver transplantation as a means of improving graft survival. HOCs were activated and isolated using a modified 2-acetylaminofluorene/partial hepatectomy (2-AAF/PH model in male Lewis rats. A HOC line stably expressing the HGF gene was established following stable transfection of the pBLAST2-hHGF plasmid. Our results demonstrated that hHGF-modified HOCs could efficiently differentiate into hepatocytes and bile duct epithelial cells in vitro. Administration of HOCs at the time of liver transplantation induced a wider distribution of SRY-positive donor cells in liver tissues. Administration of hHGF-HOC at the time of transplantation remarkably prolonged the median survival time and improved liver function for recipients compared to these parameters in the other treatment groups (P<0.05. Moreover, hHGF-HOC administration at the time of liver transplantation significantly suppressed elevation of interleukin-2 (IL-2, tumor necrosis factor-α (TNF-α and interferon-γ (IFN-γ levels while increasing the production of IL-10 and TGF-β1 (P<0.05. HOC or hHGF-HOC administration promoted cell proliferation, reduced cell apoptosis, and decreased liver allograft rejection rates. Furthermore, hHGF-modified HOCs more efficiently reduced acute allograft rejection (P<0.05 versus HOC transplantation only. Our results indicate that the combination of hHGF-modified HOCs with liver transplantation decreased host anti-graft immune responses resulting in a reduction of allograft rejection rates and prolonging graft survival in recipient rats. This suggests that HOC-based cell transplantation therapies can be developed as a means of treating severe liver

  18. Prevention of pure red cell aplasia after major or bidirectional ABO blood group incompatible hematopoietic stem cell transplantation by pretransplant reduction of host anti-donor isoagglutinins

    OpenAIRE

    Stussi, G.; Halter, J; Bucheli, E; Valli, P V; Seebach, L; Gmür, J; Gratwohl, A; Passweg, J. R.; Seebach, J.D.

    2009-01-01

    BACKGROUND: Persistent anti-donor isoagglutinins after major ABO blood group incompatible hematopoietic stem cell transplantation may cause delayed red blood cell engraftment and post-transplant pure red cell aplasia. DESIGN AND METHODS: We investigated the effect of pretransplant anti-donor isoagglutinin reduction by in vivo absorption and/or plasmapheresis on the incidence of pure red cell aplasia and the time to red blood cell engraftment in 153 hematopoietic stem cell transplant recipient...

  19. Severe cutaneous human papilloma virus infection associated with Natural Killer cell deficiency following stem cell transplantation for severe combined immunodeficiency

    Science.gov (United States)

    Kamili, Qurat-ul-Ain; Seeborg, Filiz O; Saxena, Kapil; Nicholas, Sarah K; Banerjee, Pinaki P; Angelo, Laura S; Mace, Emily M; Forbes, Lisa R; Martinez, Caridad; Wright, Teresa S; Orange, Jordan S.; Hanson, Imelda Celine

    2016-01-01

    Capsule Summary The authors identify Natural Killer cell deficiency in post-transplant severe combined immunodeficiency patients who developed severe human papilloma virus infections as a long term complication. PMID:25159470

  20. Feasibility of Bone Marrow Stromal Cells Autologous Transplantation for Dilated Cardiomyopathy

    Institute of Scientific and Technical Information of China (English)

    ZHOU Cheng; YANG Chenyuan; XIAO Shiliang; FEI Hongwen

    2007-01-01

    The feasibility of bone marrow stromal cells autologous transplantation for rabbit model of dilated cardiomyopathy induced by adriamycin was studied. Twenty rabbits received 2 mg/kg of adriamycin intravenously once a week for 8 weeks (total dose, 16 mg/kg) to induce the cardiomyopathy model with the monitoring of cardiac function by transthoracic echocardiography. Marrow stromal cells were isolated from cell-transplanted group rabbits and were culture-expanded on the 8th week. On the 10th week, cells were labeled with 4,6-diamidino-2-phenylindole (DAPI), and then injected into the myocardium of the same rabbits. The results showed that viable cells labeled with DAPI could be identified in myocardium at 2nd week after transplantation. Histological findings showed the injury of the myocardium around the injection site was relieved with less apoptosis and more expression of bcl-2. The echocardiography found the improvement of local tissue movement from (2.12±0.51) cm/s to (3.81±0.47) cm/s (P<0.05) around the inject site, but no improvement of heart function as whole. It was concluded bone marrow stromal cells transplantation for dilated cardiomyopathy was feasibe. The management of cells in vitro, the quantity and the pattern of the cells transplantation and the action mechanism still need further research.

  1. Germ cell transplantation as a potential biotechnological approach to fish reproduction.

    Science.gov (United States)

    Lacerda, S M S N; Costa, G M J; Campos-Junior, P H A; Segatelli, T M; Yazawa, R; Takeuchi, Y; Morita, T; Yoshizaki, G; França, L R

    2013-02-01

    Although the use of germ cell transplantation has been relatively well established in mammals, the technique has only been adapted for use in fish after entering the 2000s. During the last decade, several different approaches have been developed for germ cell transplantation in fish using recipients of various ages and life stages, such as blastula-stage embryos, newly hatched larvae and sexually mature specimens. As germ cells can develop into live organisms through maturation and fertilization processes, germ cell transplantation in fish has opened up new avenues of research in reproductive biotechnology and aquaculture. For instance, the use of xenotransplantation in fish has lead to advances in the conservation of endangered species and the production of commercially valuable fish using surrogated recipients. Further, this could also facilitate the engineering of transgenic fish. However, as is the case with mammals, knowledge regarding the basic biology and physiology of germline stem cells in fish remains incomplete, imposing a considerable limitation on the application of germ cell transplantation in fish. Furthering our understanding of germline stem cells would contribute significantly to advances regarding germ cell transplantation in fish.

  2. Therapeutic outcomes of transplantation of amniotic fluid-derived stem cells in experimental ischemic stroke

    Directory of Open Access Journals (Sweden)

    Naoki eTajiri

    2014-08-01

    Full Text Available Accumulating preclinical evidence suggests the use of amnion as a source of stem cells for investigations of basic science concepts related to developmental cell biology, but also for stem cells’ therapeutic applications in treating human disorders. We previously reported isolation of viable rat amniotic fluid-derived stem (AFS cells. Subsequently, we recently reported the therapeutic benefits of intravenous transplantation of AFS cells in a rodent model of ischemic stroke. Parallel lines of investiagtions have provided safety and efficacy of stem cell therapy for treating stroke and other neurological disorders. This review article highlights characterization of AFS cells’ phenotype and their transplant-mediated functional effects, the need for investigations of mechanisms underlying AFS cells’ therapeutic benefits and discusses lab-to-clinic translational gating items in an effort to optimize the clinical application of cell transplantation for stroke.

  3. Chitosan-collagen porous scaffold and bone marrow mesenchymal stem cell transplantation for ischemic stroke

    Directory of Open Access Journals (Sweden)

    Feng Yan

    2015-01-01

    Full Text Available In this study, we successfully constructed a composite of bone marrow mesenchymal stem cells and a chitosan-collagen scaffold in vitro, transplanted either the composite or bone marrow mesenchymal stem cells alone into the ischemic area in animal models, and compared their effects. At 14 days after co-transplantation of bone marrow mesenchymal stem cells and the hitosan-collagen scaffold, neurological function recovered noticeably. Vascular endothelial growth factor expression and nestin-labeled neural precursor cells were detected in the ischemic area, surrounding tissue, hippocampal dentate gyrus and subventricular zone. Simultaneously, a high level of expression of glial fibrillary acidic protein and a low level of expression of neuron-specific enolase were visible in BrdU-labeled bone marrow mesenchymal stem cells. These findings suggest that transplantation of a composite of bone marrow mesenchymal stem cells and a chitosan-collagen scaffold has a neuroprotective effect following ischemic stroke.

  4. Chitosan-collagen porous scaffold and bone marrow mesenchymal stem cell transplantation for ischemic stroke

    Institute of Scientific and Technical Information of China (English)

    Feng Yan; Wei Yue; Yue-lin Zhang; Guo-chao Mao; Ke Gao; Zhen-xing Zuo; Ya-jing Zhang; Hui Lu

    2015-01-01

    In this study, we successfully constructed a composite of bone marrow mesenchymal stem cells and a chitosan-collagen scaffoldin vitro, transplanted either the composite or bone marrow mesenchymal stem cells alone into the ischemic area in animal models, and compared their effects. At 14 days after co-transplantation of bone marrow mesenchymal stem cells and the hi-tosan-collagen scaffold, neurological function recovered noticeably. Vascular endothelial growth factor expression and nestin-labeled neural precursor cells were detected in the ischemic area, surrounding tissue, hippocampal dentate gyrus and subventricular zone. Simultaneously, a high level of expression of glial ifbrillary acidic protein and a low level of expression of neuron-spe-ciifc enolase were visible in BrdU-labeled bone marrow mesenchymal stem cells. These ifndings suggest that transplantation of a composite of bone marrow mesenchymal stem cells and a chi-tosan-collagen scaffold has a neuroprotective effect following ischemic stroke.

  5. Long-term Survival, Organ Function, and Malignancy after Hematopoietic Stem Cell Transplantation for Fanconi Anemia.

    Science.gov (United States)

    Bonfim, Carmem; Ribeiro, Lisandro; Nichele, Samantha; Bitencourt, Marco; Loth, Gisele; Koliski, Adriana; Funke, Vaneuza A M; Pilonetto, Daniela V; Pereira, Noemi F; Flowers, Mary E D; Velleuer, Eunike; Dietrich, Ralf; Fasth, Anders; Torres-Pereira, Cassius C; Pedruzzi, Paola; Eapen, Mary; Pasquini, Ricardo

    2016-07-01

    We report on long-term survival in 157 patients with Fanconi anemia (FA) who survived 2 years or longer after their first transplantation with a median follow-up of 9 years. Marrow failure (80%) was the most common indication for transplantation. There were 20 deaths beyond 2 years after transplantation, with 12 of the deaths occurring beyond 5 years after transplantation. Donor chimerism was available for 149 patients: 112 (76%) reported > 95% chimerism, 27 (18%) reported 90% to 95% chimerism, and 8 (5%) reported 20% to 89% donor chimerism. Two patients have < 20% donor chimerism. The 10- and 15-year probabilities of survival were 90% and 79%, respectively. Results of multivariate analysis showed higher mortality risks for transplantations before 2003 (hazard ratio [HR], 7.87; P = .001), chronic graft-versus-host disease (GVHD) (HR, 3.80; P = .004) and squamous cell carcinoma after transplantation (HR, 38.17; P < .0001). The predominant cause of late mortality was squamous cell carcinoma, with an incidence of 8% and 14% at 10 and 15 years after transplantation, respectively, and was more likely to occur in those with chronic GVHD. Other causes of late mortality included chronic GVHD, infection, graft failure, other cancers, and hemorrhage. Although most patients are disease free and functional long term, our data support aggressive surveillance for long periods to identify those at risk for late mortality.

  6. Cognitive improvement following transvenous adipose-derived mesenchymal stem cell transplantation in a rat model of traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    Dongfei Li; Chun Yang; Rongmei Qu; Huiying Yang; Meichun Yu; Hui Tao; Jingxing Dai; Lin Yuan

    2011-01-01

    The effects of adipose-derived mesenchymal stem cell (ADMSC) transplantation for the repair of traumatic brain injury remain poorly understood. The present study observed neurological functional changes in a rat model of traumatic brain injury following ADMSC transplantation via the tail vein.Cell transplants were observed in injured cerebral cortex, and expression of brain-derived nerve growth factor was significantly increased in the injured hippocampus following transplantation. Results demonstrated that transvenous ADMSC transplants migrated to the injured cerebral cortex and significantly improved cognitive function.

  7. Rescue of salivary gland function after stem cell transplantation in irradiated glands.

    Directory of Open Access Journals (Sweden)

    Isabelle M A Lombaert

    Full Text Available Head and neck cancer is the fifth most common malignancy and accounts for 3% of all new cancer cases each year. Despite relatively high survival rates, the quality of life of these patients is severely compromised because of radiation-induced impairment of salivary gland function and consequential xerostomia (dry mouth syndrome. In this study, a clinically applicable method for the restoration of radiation-impaired salivary gland function using salivary gland stem cell transplantation was developed. Salivary gland cells were isolated from murine submandibular glands and cultured in vitro as salispheres, which contained cells expressing the stem cell markers Sca-1, c-Kit and Musashi-1. In vitro, the cells differentiated into salivary gland duct cells and mucin and amylase producing acinar cells. Stem cell enrichment was performed by flow cytrometric selection using c-Kit as a marker. In vitro, the cells differentiated into amylase producing acinar cells. In vivo, intra-glandular transplantation of a small number of c-Kit(+ cells resulted in long-term restoration of salivary gland morphology and function. Moreover, donor-derived stem cells could be isolated from primary recipients, cultured as secondary spheres and after re-transplantation ameliorate radiation damage. Our approach is the first proof for the potential use of stem cell transplantation to functionally rescue salivary gland deficiency.

  8. T CELL REPERTOIRE COMPLEXITY IN SEVER COMBINED IMMUNODEFICIENCY PATIENTS AFTER BONE MARROW TRANSPLANTATION

    Institute of Scientific and Technical Information of China (English)

    曹水; 李晓静

    2003-01-01

    Objective. To study thymus-dependent T cell development and T cell repertoire in human sever combined immunodeficiency (SCID) patients after HLA-identical or haploidentical T cell-depleted allogeneic bone marrow transplantation (BMT). Methods. Blood samples were obtained from 15 SCID patients before transplantation and at varying intervals thereafter. Quantitative competitive PCR assay and immunoscope analysis of the T cell receptor (TCR) Vβ repertoire were performed. Results. Before and within the first 100 days after transplantation, patients' peripheral blood mononuclear cell (PBMC) presented an oligoclonal or polyclonal skewed T cell repertoire, low T cell receptor excision circles (TRECs) values and predominance of CD45RO+ T cell. In contrast, the presence of high numbers of CD45RA+ T cells in bone marrow(BM) circulation reconstituted SCID patients (>100 days post-transplantation) correlated with active T cell production by the thymus as revealed by high TREC values, and a polyclonal T cell repertoire demonstrated by a Gaussian distribution of Vβ-specific peaks. Conclusions. Within one year after BMT, a normal T cell repertoire develops in SCID patients as a result of thymic output. The T cell receptor diversity is highly and positively correlated in these patients with TREC levels.

  9. 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

  10. Influences of olfactory ensheathing cells transplantation on axonal regeneration in spinal cord of adult rats

    Institute of Scientific and Technical Information of China (English)

    沈慧勇; 唐勇; 吴燕峰; 陈燕涛; 程志安

    2002-01-01

    To observe whether olfactory ensheathing cells could be used to promote axonal regeneration in a spontaneously nonregenerating system. Methods: After laminectomy at the lower thoracic level, the spinal cords of adult rats were exposed and completely transected at T10. A suspension of ensheathing cells was injected into the lesion site in 12 adult rats, and control D/F-12 (1∶1 mixture of DMEM and Hams F-12) was injected in 12 adult rats. Six weeks and ten weeks after cell transplantation, the rats were evaluated by climbing test and motor evoked potentials (MEPs) monitoring. The samples were procured and studied with histologicl and immunohistochemical methods. Results: At the 6th week after cell transplantation, all the rats in both the transplanted and control groups were paraplegic and the MEPs could not be recorded. At the 10th week after cell transplantation, of 7 rats in the control group, 2 rats had muscles contraction of the lower extremities, 2 rats had hips and/or knees active movement; and 5 rats MEPs could be recorded in the hind limbs in the transplanted group (n=7). None of the rats in the control group had functional improvement and no MEPs recorded (n=7). Numerous regenerating axons were observed through the transplantation and continued to regenerate into the denervated host tract. Cell labelling using anti-Myelin Basic Protein (MBP) and anti-Nerve Growth Factor Receptor (anti-NGFR) indicated that the regenerated axons were derived from the appropriate neuronal source and that donor cells migrated into the denervated host tract. But axonal degeneration existed and regenerating axons were not observed within the spinal cords of the adult rats with only D/F-12 injection. Conclusions: The axonal regeneration in the transected adult rat spinal cord is possible after ensheathing cells transplantation.

  11. Pregnancy after allogeneic hematopoietic stem cell transplantation in a Fanconi anemia patient

    Directory of Open Access Journals (Sweden)

    Atashkhoei S

    2017-01-01

    Full Text Available Simin Atashkhoei, Solmaz Fakhari, Eissa Bilehjani, Haleh Farzin Department of Anesthesiology, Al-Zahra Hospital, Tabriz University of Medical Sciences, Tabriz, Iran Abstract: Pregnancy in patients with Fanconi anemia (FA is rare. However, there are reports of successful pregnancy in Fanconi patients after bone marrow transplantation (BMT, hematopoietic stem cell transplantation. We describe the case of a term pregnant woman with FA who was treated with BMT 2 years earlier. She underwent successful delivery with cesarean section using spinal anesthesia without any complications. Keywords: Fanconi anemia, bone marrow transplantation, pregnancy, cesarean section, spinal anesthesia

  12. The Integration and Functional Evaluation of Rabbit Pacing Cells Transplanted into the Left Ventricular Free Wall

    Directory of Open Access Journals (Sweden)

    Zhihui Zhang, Zhiyuan Song, Jun Cheng, Yaoming Nong, Lu Wei, Changhai Zhang

    2012-01-01

    Full Text Available To evaluate the feasibility of cell transplantation to treat bradyarrhythmia, we analyzed the in vivo integration and pacing function after transplantation of mHCN4-modified rabbit bone marrow mesenchymal stem cells (MSCs into the rabbit left ventricle free wall epicardium. In our investigation, we injected MSCs transduced with or without mHCN4 into the rabbit left ventricle free wall epicardium. Chemical ablation of the sinoatrial node was performed and bilateral vagus nerves were sequentially stimulated to observe premature left ventricular contraction or left ventricular rhythm. We found that the mHCN4-transduced MSC group had a significantly higher ventricular rate and a shorter QRS duration than that of the control and EGFP group. Furthermore, the mHCN4-transduced MSCs, but not the control cells, gradually adapted long-spindle morphology and became indistinguishable from adjacent ventricle myocytes. The modified MSCs showed pacing function approximately 1 week after transplantation and persisted at least 4 weeks after transplantation. In conclusion, a bradyarrhythmia model can be successfully established by chemical ablation of the sinoatrial node and sequential bilateral vagus nerve stimulation. The mHCN4-modified rabbit MSCs displayed evident dynamic morphology changes after being transplanted into rabbit left ventricle free wall epicardium. Our studies may provide a promising strategy of using modified stem cell transplantation to treat bradyarrhythmia.

  13. In vivo cell kinetics of the bone marrow transplantation using dual colored transgenic rat system

    Science.gov (United States)

    Kai, Kotaro; Teraoka, Satoshi; Adachi, Yasushi; Ikehara, Susumu; Murakami, Takashi; Kobayashi, Eiji

    2008-02-01

    Because bone marrow is an adequate site for bone marrow stem cells, intra-bone marrow - bone marrow transplantation (IBM-BMT) is an efficient strategy for bone marrow transplantation (BMT). However, the fate of the transplanted cells remains unclear. Herein, we established a dual-colored transgenic rat system utilizing green fluorescent protein (GFP) and a luciferase (luc) marker. We then utilized this system to investigate the in vivo kinetics of transplanted bone marrow cells (BMCs) after authentic intravenous (IV)-BMT or IBM-BMT. The in vivo fate of the transplanted cells was tracked using an in vivo luminescent imaging technique; alterations in peripheral blood chimerism were also followed using flow cytometry. IBM-BMT and IV-BMT were performed using syngeneic and allogeneic rat combinations. While no difference in the proliferation pattern was observed between the two treatment groups at 7 days after BMT, different distribution patterns were clearly observed during the early phase. In the IBM-BMT-treated rats, the transplanted BMCs were engrafted immediately at the site of the injected bone marrow and expanded more rapidly than in the IV-BMT-treated rats during this phase. Graft-versus-host disease was also visualized. Our bio-imaging system using dual-colored transgenic rats is a powerful tool for performing quantitative and morphological assessments in vivo.

  14. Progenitor cells trapped in marrow filters can reduce GvHD and transplant mortality.

    Science.gov (United States)

    Vicente, D; Podestà, M; Pitto, A; Pozzi, S; Lucchetti, S; Lamparelli, T; Tedone, E; Ibatici, A; Figari, O; Frassoni, F; Van Lint, M T; Piaggio, G; Sacchi, N; Bacigalupo, A

    2006-07-01

    A bone marrow harvest is filtered either in the operating room, in the laboratory or during infusion to the patient. Filters are usually discarded. Little is known of haemopoietic progenitor cells (HPCs) trapped in the filters. The aim of the study was to evaluate HPC content in the filters and to assess the outcome of transplants with filter-discarded or filter-recovered cells. Haemopoietic progenitors were grown from filters of 19 marrow transplants. We then compared the outcome of 39 filter-recovered transplants from HLA-identical siblings (years 2001-2004) with a matched cohort of 43 filter-discarded marrow grafts (years 1997-2000). Filters contained on average 21% long-term culture-initiating cells (LTC-IC) and 15% fibroblasts colony-forming units (CFU-F) of the total progenitor cell content. Filter-discarded transplants had significantly more grade II-IV graft-versus-host disease (GvHD) (42 vs 15%, P=0.008) as compared to filter-recovered transplants, and more transplant-related mortality (TRM) (20 vs 3%, P=0.04). The actuarial survival at 5 years is 69 vs 87%, respectively (P=0.15). This study suggests that a significant proportion of LTC-IC is lost in the filters together with CFU-F. Recovery and add back of progenitors trapped in the filters may reduce GvHD and TRM.

  15. Proteome Profiling in Lung Injury after Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Bhargava, Maneesh; Viken, Kevin J; Dey, Sanjoy; Steinbach, Michael S; Wu, Baolin; Jagtap, Pratik D; Higgins, LeeAnn; Panoskaltsis-Mortari, Angela; Weisdorf, Daniel J; Kumar, Vipin; Arora, Mukta; Bitterman, Peter B; Ingbar, David H; Wendt, Chris H

    2016-08-01

    Pulmonary complications due to infection and idiopathic pneumonia syndrome (IPS), a noninfectious lung injury in hematopoietic stem cell transplant (HSCT) recipients, are frequent causes of transplantation-related mortality and morbidity. Our objective was to characterize the global bronchoalveolar lavage fluid (BALF) protein expression of IPS to identify proteins and pathways that differentiate IPS from infectious lung injury after HSCT. We studied 30 BALF samples from patients who developed lung injury within 180 days of HSCT or cellular therapy transfusion (natural killer cell transfusion). Adult subjects were classified as having IPS or infectious lung injury by the criteria outlined in the 2011 American Thoracic Society statement. BALF was depleted of hemoglobin and 14 high-abundance proteins, treated with trypsin, and labeled with isobaric tagging for relative and absolute quantification (iTRAQ) 8-plex reagent for two-dimensional capillary liquid chromatography (LC) and data dependent peptide tandem mass spectrometry (MS) on an Orbitrap Velos system in higher-energy collision-induced dissociation activation mode. Protein identification employed a target-decoy strategy using ProteinPilot within Galaxy P. The relative protein abundance was determined with reference to a global internal standard consisting of pooled BALF from patients with respiratory failure and no history of HSCT. A variance weighted t-test controlling for a false discovery rate of ≤5% was used to identify proteins that showed differential expression between IPS and infectious lung injury. The biological relevance of these proteins was determined by using gene ontology enrichment analysis and Ingenuity Pathway Analysis. We characterized 12 IPS and 18 infectious lung injury BALF samples. In the 5 iTRAQ LC-MS/MS experiments 845, 735, 532, 615, and 594 proteins were identified for a total of 1125 unique proteins and 368 common proteins across all 5 LC-MS/MS experiments. When comparing IPS to

  16. Employment Status as an Indicator of Recovery and Function One Year after Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Morrison, Eleshia J; Ehlers, Shawna L; Bronars, Carrie A; Patten, Christi A; Brockman, Tabetha A; Cerhan, James R; Hogan, William J; Hashmi, Shahrukh K; Gastineau, Dennis A

    2016-09-01

    Employment after hematopoietic stem cell transplantation (HSCT) is an indicator of post-transplantation recovery and function, with economic and social implications. As survival rates for HSCT continue to improve, greater emphasis can be placed on factors affecting the quality of post-transplantation survival, including the ability to resume employment. A sample of recipients of autologous or allogeneic HSCT was accrued (n = 1000) to complete a longitudinal lifestyle survey before transplantation and at 1 year after transplantation. The present study examines associations between employment and patient characteristics, disease variables, illness status, and quality of life among 1-year survivors (n = 702). Participants had a mean age of 55 years (range, 18 to 78) and were predominately male (59.7%), married/partnered (77.1%), and non-Hispanic Caucasian (89.5%); most (79.4%) had received autologous transplantation. Of the 690 participants reporting some form of employment before illness diagnosis, 62.4% had returned to work by 1 year after HSCT. Full-time employment at 1 year after HSCT was significantly associated with remission of illness, improved illness, fewer post-transplantation hospitalizations, less fatigue and pain, higher quality of life, and higher rating of perceived health. Those unemployed because of their health reported the highest rates of fatigue and pain and lowest quality of life, and they were most likely to report poor perceived health. These findings highlight work reintegration as an important outcome and marker of survivors' overall adjustment after transplantation. Identifying factors affecting post-transplantation employment offers opportunities for behavioral interventions to target modifiable risk factors to optimize post-transplantation survivorship, inclusive of increased rates of return to work and decreased rates of associated disability.

  17. Advances in haplo-identical stem cell transplantation in adults with high-risk hematological malignancies

    Institute of Scientific and Technical Information of China (English)

    Michael; J; Ricci; Jeffrey; A; Medin; Ronan; S; Foley

    2014-01-01

    Allogeneic bone marrow transplant is a life-saving procedure for adults and children that have high-risk or relapsed hematological malignancies. Incremental advances in the procedure, as well as expanded sources of donor hematopoietic cell grafts have significantly improved overall rates of success. Yet, the outcomes for patients for whom suitable donors cannot be found remain a significant limitation. These patients may benefit from a hematopoietic cell transplant wherein a relative donor is fully haplotype mismatched. Previously this procedure was limited by graft rejection, lethal graft-versus-host disease, and increased treatmentrelated toxicity. Recent approaches in haplo-identical transplantation have demonstrated significantly improved outcomes. Based on years of incremental preclinical research into this unique form of bone marrow transplant, a range of approaches have now been studied in patients in relatively large phase Ⅱ trials that will be summarized in this review.

  18. Anti-T-cell antibodies for the treatment of acute rejection after renal transplantation.

    NARCIS (Netherlands)

    Hoogen, M.W.F. van den; Hoitsma, A.J.; Hilbrands, L.B.

    2012-01-01

    INTRODUCTION: Given the central role of T cells in the alloimmune response, anti-T-cell antibodies retain a prominent place in the treatment of renal allograft rejection. During the past decades, many anti-T-cell antibodies have emerged and subsequently left the field of solid organ transplantation,

  19. Quantitative proteomics reveals differential regulation of protein expression in recipient myocardium after trilineage cardiovascular cell transplantation.

    Science.gov (United States)

    Chang, Ying-Hua; Ye, Lei; Cai, Wenxuan; Lee, Yoonkyu; Guner, Huseyin; Lee, Youngsook; Kamp, Timothy J; Zhang, Jianyi; Ge, Ying

    2015-08-01

    Intramyocardial transplantation of cardiomyocytes (CMs), endothelial cells (ECs), and smooth muscle cells (SMCs) derived from human induced pluripotent stem cells (hiPSCs) has beneficial effects on the post-infarction heart. However, the mechanisms underlying the functional improvements remain undefined. We employed large-scale label-free quantitative proteomics to identify proteins that were differentially regulated following cellular transplantation in a swine model of myocardial infarction (MI). We identified 22 proteins that were significantly up-regulated after trilineage cell transplantation compared to both MI and Sham groups. Among them, 12 proteins, including adenylyl cyclase-associated protein 1 and tropomodulin-1, are associated with positive regulation of muscular contraction whereas 11 proteins, such as desmoplakin and zyxin, are involved in embryonic and muscular development and regeneration. Moreover, we identified 21 proteins up-regulated and another 21 down-regulated in MI, but reversed after trilineage cell transplantation. Proteins up-regulated after MI but reversed by transplantation are related to fibrosis and apoptosis. Conversely, proteins down-regulated in MI but restored after cell therapy are regulators of protein nitrosylation. Our results show that the functionally beneficial effects of trilineage cell therapy are accompanied by differential regulation of protein expression in the recipient myocardium, which may contribute to the improved cardiac function.

  20. Importance of killer immunoglobulin-like receptors in allogeneic hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Danilo Santana Alessio Franceschi

    2011-01-01

    Full Text Available Hematopoietic stem cell transplantation is the treatment of choice for many hematologic diseases, such as multiple myeloma, bone marrow aplasia and leukemia. Human leukocyte antigen (HLA compatibility is an important tool to prevent post-transplant complications such as graft rejection and graft-versus-host disease, but the high rates of relapse limit the survival of transplant patients. Natural Killer cells, a type of lymphocyte that is a key element in the defense against tumor cells, cells infected with viruses and intracellular microbes, have different receptors on their surfaces that regulate their cytotoxicity. Killer immunoglobulin-like receptors are the most important, interacting consistently with human leukocyte antigen class I molecules present in other cells and thus controlling the activation of natural killer cells. Several studies have shown that certain combinations of killer immunoglobulin-like receptors and human leukocyte antigens (in both donors and recipients can affect the chances of survival of transplant patients, particularly in relation to the graft-versusleukemia effect, which may be associated to decreased relapse rates in certain groups. This review aims to shed light on the mechanisms and effects of killer immunoglobulin-like receptors - human leukocyte antigen associations and their implications following hematopoietic stem cell transplantation, and to critically analyze the results obtained by the studies presented herein.

  1. Predicted molecular signaling guiding photoreceptor cell migration following transplantation into damaged retina

    Science.gov (United States)

    Unachukwu, Uchenna John; Warren, Alice; Li, Ze; Mishra, Shawn; Zhou, Jing; Sauane, Moira; Lim, Hyungsik; Vazquez, Maribel; Redenti, Stephen

    2016-03-01

    To replace photoreceptors lost to disease or trauma and restore vision, laboratories around the world are investigating photoreceptor replacement strategies using subretinal transplantation of photoreceptor precursor cells (PPCs) and retinal progenitor cells (RPCs). Significant obstacles to advancement of photoreceptor cell-replacement include low migration rates of transplanted cells into host retina and an absence of data describing chemotactic signaling guiding migration of transplanted cells in the damaged retinal microenvironment. To elucidate chemotactic signaling guiding transplanted cell migration, bioinformatics modeling of PPC transplantation into light-damaged retina was performed. The bioinformatics modeling analyzed whole-genome expression data and matched PPC chemotactic cell-surface receptors to cognate ligands expressed in the light-damaged retinal microenvironment. A library of significantly predicted chemotactic ligand-receptor pairs, as well as downstream signaling networks was generated. PPC and RPC migration in microfluidic ligand gradients were analyzed using a highly predicted ligand-receptor pair, SDF-1α - CXCR4, and both PPCs and RPCs exhibited significant chemotaxis. This work present a systems level model and begins to elucidate molecular mechanisms involved in PPC and RPC migration within the damaged retinal microenvironment.

  2. Bone marrow cells produce nerve growth factor and promote angiogenesis around transplanted islets

    Institute of Scientific and Technical Information of China (English)

    Naoaki; Sakata; Nathaniel; K; Chan; John; Chrisler; Andre; Obenaus; Eba; Hathout

    2010-01-01

    AIM:To clarify the mechanism by which bone marrow cells promote angiogenesis around transplanted islets.METHODS: Streptozotocin induced diabetic BALB/ c mice were transplanted syngeneically under the kidney capsule with the following: (1) 200 islets (islet group: n=12), (2) 1-5×106 bone marrow cells (bone marrow group: n=11), (3) 200 islets and 1-5×106 bone marrow cells (islet + bone marrow group: n= 13), or (4) no cells (sham group:n=5). All mice were evaluated for blood glucose, serum insulin, serum nerve...

  3. Autologous Stem Cell Transplantation in Patients with Acute Myeloid Leukemia: a Single-Centre Experience

    Directory of Open Access Journals (Sweden)

    Kakucs Enikő

    2013-04-01

    Full Text Available Introduction: Autologous haemopoietic stem cell transplantation (SCT is an important treatment modality for patients with acute myeloid leukemia with low and intermediate risk disease. It has served advantages over allogenic transplantation, because it does not need a matched donor, there is no graft versus host disease, there are less complications and a faster immune reconstitution than in the allo-setting. The disadvantage is the lack of the graft versus leukaemia effect.

  4. Pregnancy after allogeneic hematopoietic stem cell transplantation in a Fanconi anemia patient

    OpenAIRE

    Atashkhoei S; Fakhari S; Bilehjani E; Farzin H

    2017-01-01

    Simin Atashkhoei, Solmaz Fakhari, Eissa Bilehjani, Haleh Farzin Department of Anesthesiology, Al-Zahra Hospital, Tabriz University of Medical Sciences, Tabriz, Iran Abstract: Pregnancy in patients with Fanconi anemia (FA) is rare. However, there are reports of successful pregnancy in Fanconi patients after bone marrow transplantation (BMT, hematopoietic stem cell transplantation). We describe the case of a term pregnant woman with FA who was treated with BMT 2 years earlie...

  5. Pregnancy after allogeneic hematopoietic stem cell transplantation in a Fanconi anemia patient

    OpenAIRE

    Atashkhoei,Simin; Fakhari,Solmaz; Bilehjani,Eissa; Farzin,Haleh

    2017-01-01

    Simin Atashkhoei, Solmaz Fakhari, Eissa Bilehjani, Haleh Farzin Department of Anesthesiology, Al-Zahra Hospital, Tabriz University of Medical Sciences, Tabriz, Iran Abstract: Pregnancy in patients with Fanconi anemia (FA) is rare. However, there are reports of successful pregnancy in Fanconi patients after bone marrow transplantation (BMT, hematopoietic stem cell transplantation). We describe the case of a term pregnant woman with FA who was treated with BMT 2&n...

  6. Hemorrhagic cystitis after hematopoietic stem cell trans-plantation: much progress and many remaining issues

    Institute of Scientific and Technical Information of China (English)

    Edmund K. Waller

    2007-01-01

    @@ The manuscript by Xu et al1 addresses an important question in the field of allogeneic hematopoietic progenitor cell transplantation (HPCT): how to identify those patients at risk for hemmoraghic cystitis. The authors performed a retrospective analysis of 250 patients undergoing allogeneic HPCT following myeloablative conditioning with busulfan and cyclophosphamide using a standard post-transplant immunoprophylaxis with cyclosporine, short-course methotrexate and mycophenylate.

  7. The role of hematopoietic stem cell transplantation for type 1 diabetes mellitus

    OpenAIRE

    2008-01-01

    In this review, we present 1) scientific basis for the use of high dose immunosuppression followed by autologous peripheral blood hematopoietic stem cell transplantation for newly diagnosed type 1 diabetes mellitus, 2) an update of clinical and laboratory outcomes in 21 patients transplanted at the University Hospital of the Ribeirão Preto Medical School, University of São Paulo, Brazil, including 6 relapses in patients without previous ketoacidosis and 3) a discussion of future prospectives ...

  8. Herpesvirus-Associated Central Nervous System Diseases after Allogeneic Hematopoietic Stem Cell Transplantation

    OpenAIRE

    2013-01-01

    Herpesvirus infections of the central nervous system (CNS) are associated with encephalitis/myelitis and lymphoproliferative diseases in immunocompromised individuals. As of now, data of herpesvirus-associated CNS diseases in transplant recipients is limited. Hence, in this prospective study, we investigated the incidence of herpesvirus-associated CNS diseases and explored the diagnosis of these diseases in 281 allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Herpesv...

  9. Propofol promotes spinal cord injury repair by bone marrow mesenchymal stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Ya-jing Zhou

    2015-01-01

    Full Text Available Propofol is a neuroprotective anesthetic. Whether propofol can promote spinal cord injury repair by bone marrow mesenchymal stem cells remains poorly understood. We used rats to investigate spinal cord injury repair using bone marrow mesenchymal stem cell transplantation combined with propofol administration via the tail vein. Rat spinal cord injury was clearly alleviated; a large number of newborn non-myelinated and myelinated nerve fibers appeared in the spinal cord, the numbers of CM-Dil-labeled bone marrow mesenchymal stem cells and fluorogold-labeled nerve fibers were increased and hindlimb motor function of spinal cord-injured rats was markedly improved. These improvements were more prominent in rats subjected to bone marrow mesenchymal cell transplantation combined with propofol administration than in rats receiving monotherapy. These results indicate that propofol can enhance the therapeutic effects of bone marrow mesenchymal stem cell transplantation on spinal cord injury in rats.

  10. Umbilical cord mesenchymal stem cell transplantation for the treatment of Duchenne muscular dystrophy

    Institute of Scientific and Technical Information of China (English)

    Xiaofeng Yang; Yanxiang Wu; Xinping Liu; Yifeng Xu; Naiwu Lü; Yibin Zhang; Hongmei Wang; Xin Lü; Jiping Cui; Jinxu Zhou; Hong Shan

    2011-01-01

    Due to their relative abundance, stable biological properties and excellent reproductive activity,umbilical cord mesenchymal stem cells have previously been utilized for the treatment of Duchenne muscular dystrophy, which is a muscular atrophy disease. Three patients who were clinically and pathologically diagnosed with Duchenne muscular dystrophy were transplanted with umbilical cord mesenchymal stem cells by intravenous infusion, in combination with multi-point intramuscular injection. They were followed up for 12 months after cell transplantation. Results showed that clinical symptoms significantly improved, daily living activity and muscle strength were enhanced,the sero-enzyme, electromyogram, and MRI scans showed improvement, and dystrophin was expressed in the muscle cell membrane. Hematoxylin-eosin staining of a muscle biopsy revealed that muscle fibers were well arranged, fibrous degeneration was alleviated, and fat infiltration was improved. These pieces of evidence suggest that umbilical cord mesenchymal stem cell transplantation can be considered as a new regimen for Duchenne muscular dystrophy.

  11. Propofol promotes spinal cord injury repair by bone marrow mesenchymal stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    Ya-jing Zhou; Jian-min Liu; Shu-ming Wei; Yun-hao Zhang; Zhen-hua Qu; Shu-bo Chen

    2015-01-01

    Propofol is a neuroprotective anesthetic. Whether propofol can promote spinal cord injury repair by bone marrow mesenchymal stem cells remains poorly understood. We used rats to investigate spinal cord injury repair using bone marrow mesenchymal stem cell transplantation combined with propofol administrationvia the tail vein. Rat spinal cord injury was clearly alleviated; a large number of newborn non-myelinated and myelinated nerve ifbers appeared in the spinal cord, the numbers of CM-Dil-labeled bone marrow mesenchymal stem cells and lfuorogold-labeled nerve ifbers were increased and hindlimb motor function of spinal cord-injured rats was mark-edly improved. These improvements were more prominent in rats subjected to bone marrow mesenchymal cell transplantation combined with propofol administration than in rats receiving monotherapy. These results indicate that propofol can enhance the therapeutic effects of bone marrow mesenchymal stem cell transplantation on spinal cord injury in rats.

  12. Financial burden in recipients of allogeneic hematopoietic cell transplantation.

    Science.gov (United States)

    Khera, Nandita; Chang, Yu-hui; Hashmi, Shahrukh; Slack, James; Beebe, Timothy; Roy, Vivek; Noel, Pierre; Fauble, Veena; Sproat, Lisa; Tilburt, Jon; Leis, Jose F; Mikhael, Joseph

    2014-09-01

    Although allogeneic hematopoietic cell transplantation (HCT) is an expensive treatment for hematological disorders, little is known about the financial consequences for the patients who undergo this procedure. We analyzed factors associated with its financial burden and its impact on health behaviors of allogeneic HCT recipients. A questionnaire was retrospectively mailed to 482 patients who underwent allogeneic HCT from January 2006 to June 2012 at the Mayo Clinic, to collect information regarding current financial concerns, household income, employment, insurance, out-of-pocket expenses, and health and functional status. A multivariable logistic regression analysis identified factors associated with financial burden and treatment nonadherence. Of the 268 respondents (56% response rate), 73% reported that their sickness had hurt them financially. All patients for whom the insurance information was available (missing, n = 13) were insured. Forty-seven percent of respondents experienced financial burden, such as household income decreased by >50%, selling/mortgaging home, or withdrawing money from retirement accounts. Three percent declared bankruptcy. Younger age and poor current mental and physical functioning increased the likelihood of financial burden. Thirty-five percent of patients reported deleterious health behaviors because of financial constraints. These patients were likely to be younger, have lower education, and with a longer time since HCT. Being employed decreased the likelihood of experiencing financial burden and treatment nonadherence due to concern about costs. A significant proportion of allogeneic HCT survivors experience financial hardship despite insurance coverage. Future research should investigate potential interventions to help at-risk patients and prevent adverse financial outcomes after this life-saving procedure.

  13. The study of migration of bone mesenchymal stem cells transplanted in intervertebral discs of rabbits and expression of exogenous gene

    Institute of Scientific and Technical Information of China (English)

    Jintang Wang; Hong Zhang; Yingang Zhang; Xiaowei Zhang; Meng Li

    2006-01-01

    Objective: To explore the survival and migration of bone mesenchymal stem cells transplantated in intervertebral disc of rabbits and expression of the exogenic genes. Methods: Thirty-two rabbits were used, A randomized block design was used and discs in the same rabbit were one block,the lumbar discs from L2-3 to L5-6 were randomly divided into blank group, saline group, cell transplantation group Ⅰ and cell transplantation group Ⅱ. The fluorescence microscopy was used to determine the fluorescence of the maker protein GFP and DNA-PCR was used to analyze the copies of DNA of neomycin-resistant gene at 1, 3, 6, months after transplantation. Results: There was fluorescence in cell transplantation group Ⅰ and Ⅱ and none in blank group, saline group at 1, 3, 6 months after transplantation. In cell transplantation groups,the fluorescent distribution was more scatter with time, but no significant difference between cell groups Ⅰ and Ⅱ. The test of neomycin resistant gene expressed in cell transplantation group Ⅰ and Ⅱ and quantitative analysis showed that there was no significant difference between the cell groups Ⅰ and Ⅱ (P>0.05). Conclusion: The transplanted bone mesenchymal stem cells can survive, migrate and the transfer genes can express efficiently, it suggests that the BMSC therapy may be effective to prevent and treat intervertebral disc degeneration.

  14. NK cell subgroups, phenotype and functions after autologous stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Benedikt eJacobs

    2015-11-01

    Full Text Available High-dose chemotherapy with consecutive autologous stem cell transplantation (autoSCT is a well-established treatment option for patients suffering from malignant lymphoma or multiple myeloma. Natural killer (NK cells are an important part of the immune surveillance, and their cell number after autoSCT is predictive for progression-free and overall survival. To improve knowledge about the role of NK cells after autoSCT, we investigated different NK cell subgroups, their phenotypes and their functions in patients treated with autoSCT. Directly after leukocyte regeneration (>1000 leukocytes/μl following autoSCT, CD56++ NK cells were the major NK cell subset. Surprisingly, these cells showed unusually high surface expression levels of CD57 and KIR compared to expression levels before or at later time points after autoSCT. Moreover, these NK cells strongly up-regulated KIR2DL2/3 and KIR3DL1, whereas KIR2DL1 remained constant, indicating that this cell population arose from more immature NK cells instead of from activated mature ones. Remarkably, NK cells were already able to degranulate and produce IFN-γ and MIP-1β upon tumor interaction early after leukocyte regeneration.In conclusion, we describe an unusual up-regulation of CD57 and KIRs on CD56++ NK cells shortly after autoSCT. Importantly, these NK cells were functionally competent upon tumor interaction at this early time point.

  15. Evaluation of Quality of Life and Care Needs of Turkish Patients Undergoing Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Neslisah Yasar

    2016-01-01

    Full Text Available This descriptive study explored the quality of life and care needs of Turkish patients who underwent hematopoietic stem cell transplantation. The study sample consisted of 100 hematopoietic stem cell transplant patients. Their quality of life was assessed using Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale. The mean patient age was 44.99 ± 13.92 years. Changes in sexual functions, loss of hair, loss of taste, loss of appetite, and sleep disturbances were the most common symptoms. The quality of life of transplant patients was moderately affected; the functional well-being and social/family well-being subscales were the most adversely and least negatively affected (12.13 ± 6.88 dimensions, respectively. Being female, being between 50 and 59 years of age, being single, having a chronic disease, and having a history of hospitalization were associated with lower quality of life scores. Interventions to improve functional status, physical well-being, and emotional status of patients during the transplantation process may help patients cope with treatment-related impairments more effectively. Frequent screening and management of patient symptoms in order to help patients adapt to life following allogeneic hematopoietic stem cell transplantation are crucial for meeting care needs and developing strategies to improve their quality of life.

  16. Intracerebral neural stem cell transplantation improved the auditory of mice with presbycusis.

    Science.gov (United States)

    Ren, Hongmiao; Chen, Jichuan; Wang, Yinan; Zhang, Shichang; Zhang, Bo

    2013-01-01

    Stem cell-based regenerative therapy is a potential cellular therapeutic strategy for patients with incurable brain diseases. Embryonic neural stem cells (NSCs) represent an attractive cell source in regenerative medicine strategies in the treatment of diseased brains. Here, we assess the capability of intracerebral embryonic NSCs transplantation for C57BL/6J mice with presbycusis in vivo. Morphology analyses revealed that the neuronal rate of apoptosis was lower in the aged group (10 months of age) but not in the young group (2 months of age) after NSCs transplantation, while the electrophysiological data suggest that the Auditory Brain Stem Response (ABR) threshold was significantly decreased in the aged group at 2 weeks and 3 weeks after transplantation. By contrast, there was no difference in the aged group at 4 weeks post-transplantation or in the young group at any time post-transplantation. Furthermore, immunofluorescence experiments showed that NSCs differentiated into neurons that engrafted and migrated to the brain, even to sites of lesions. Together, our results demonstrate that NSCs transplantation improve the auditory of C57BL/6J mice with presbycusis.

  17. Transplantation of Hematopoietic Stem Cells in Human Severe Combined Immunodeficiency: Longterm Outcomes

    Science.gov (United States)

    Buckley, Rebecca H.

    2013-01-01

    Severe combined immunodeficiency (SCID) is a syndrome of diverse genetic cause characterized by profound deficiencies of T and B cell function and, in some types, also of NK cells and function. Mutations in thirteen different genes have been found to cause this condition, which is uniformly fatal in the first two years of life unless immune reconstitution can be accomplished. In the 42 years since the first bone marrow transplant was given in 1968, the standard treatment for all forms of SCID has been allogeneic bone marrow transplantation. Both HLA identical unfractionated and T cell depleted HLA haploidentical bone marrow transplants have been very successful in effecting immune reconstitution, especially if performed in the first 3.5 months of life and without pre-transplant chemotherapy. This paper summarizes the longterm outcome, according to molecular type, of 166 consecutive SCID infants given non-conditioned related donor bone marrow transplants at this institution over the past 28.3 years and reviews published reports of longterm outcomes of transplants in SCID performed at other centers. PMID:21116871

  18. Evaluation of Quality of Life and Care Needs of Turkish Patients Undergoing Hematopoietic Stem Cell Transplantation

    Science.gov (United States)

    Yasar, Neslisah

    2016-01-01

    This descriptive study explored the quality of life and care needs of Turkish patients who underwent hematopoietic stem cell transplantation. The study sample consisted of 100 hematopoietic stem cell transplant patients. Their quality of life was assessed using Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale. The mean patient age was 44.99 ± 13.92 years. Changes in sexual functions, loss of hair, loss of taste, loss of appetite, and sleep disturbances were the most common symptoms. The quality of life of transplant patients was moderately affected; the functional well-being and social/family well-being subscales were the most adversely and least negatively affected (12.13 ± 6.88) dimensions, respectively. Being female, being between 50 and 59 years of age, being single, having a chronic disease, and having a history of hospitalization were associated with lower quality of life scores. Interventions to improve functional status, physical well-being, and emotional status of patients during the transplantation process may help patients cope with treatment-related impairments more effectively. Frequent screening and management of patient symptoms in order to help patients adapt to life following allogeneic hematopoietic stem cell transplantation are crucial for meeting care needs and developing strategies to improve their quality of life. PMID:28116155

  19. Fetal progenitor cell transplantation treats methylmalonic aciduria in a mouse model

    Energy Technology Data Exchange (ETDEWEB)

    Buck, Nicole E., E-mail: nicole.buck@mcri.edu.au [Metabolic Research, Murdoch Childrens Research Institute, The University of Melbourne, Department of Paediatrics, Royal Children' s Hospital, Flemington Road, Parkville, VIC 3052 (Australia); Pennell, Samuel D.; Wood, Leonie R. [Metabolic Research, Murdoch Childrens Research Institute, The University of Melbourne, Department of Paediatrics, Royal Children' s Hospital, Flemington Road, Parkville, VIC 3052 (Australia); Pitt, James J. [Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, Royal Children' s Hospital, Parkville (Australia); Allen, Katrina J. [Gastro and Food Allergy, Murdoch Childrens Research Institute, Parkville (Australia); Peters, Heidi L. [Metabolic Research, Murdoch Childrens Research Institute, The University of Melbourne, Department of Paediatrics, Royal Children' s Hospital, Flemington Road, Parkville, VIC 3052 (Australia)

    2012-10-12

    Highlights: Black-Right-Pointing-Pointer Fetal cells were transplanted into a methylmalonic acid mouse model. Black-Right-Pointing-Pointer Cell engraftment was detected in liver, spleen and bone marrow. Black-Right-Pointing-Pointer Biochemical disease correction was measured in blood samples. Black-Right-Pointing-Pointer A double dose of 5 million cells (1 week apart) proved more effective. Black-Right-Pointing-Pointer Higher levels of engraftment may be required for greater disease correction. -- Abstract: Methylmalonic aciduria is a rare disorder caused by an inborn error of organic acid metabolism. Current treatment options are limited and generally focus on disease management. We aimed to investigate the use of fetal progenitor cells to treat this disorder using a mouse model with an intermediate form of methylmalonic aciduria. Fetal liver cells were isolated from healthy fetuses at embryonic day 15-17 and intravenously transplanted into sub-lethally irradiated mice. Liver donor cell engraftment was determined by PCR. Disease correction was monitored by urine and blood methylmalonic acid concentration and weight change. Initial studies indicated that pre-transplantation sub-lethal irradiation followed by transplantation with 5 million cells were suitable. We found that a double dose of 5 million cells (1 week apart) provided a more effective treatment. Donor cell liver engraftment of up to 5% was measured. Disease correction, as defined by a decrease in blood methylmalonic acid concentration, was effected in methylmalonic acid mice transplanted with a double dose of cells and who showed donor cell liver engraftment. Mean plasma methylmalonic acid concentration decreased from 810 {+-} 156 (sham transplanted) to 338 {+-} 157 {mu}mol/L (double dose of 5 million cells) while mean blood C3 carnitine concentration decreased from 20.5 {+-} 4 (sham transplanted) to 5.3 {+-} 1.9 {mu}mol/L (double dose of 5 million cells). In conclusion, higher levels of engraftment may

  20. Stem cell transplantation for treating spinal cord injury A literature comparison between studies of stem cells obtained from various sources

    Institute of Scientific and Technical Information of China (English)

    Liangbi Xiang; Yu Chen

    2012-01-01

    OBJECTIVE: To identify global research trends of stem cell transplantation for treating spinal cord injury using a bibliometric analysis of the Web of Science. DATA RETRIEVAL: We performed a bibliometric analysis of data retrievals for stem cell transplantation for treating spinal cord injury from 2002 to 2011 using the Web of Science. SELECTION CRITERIA: Inclusion criteria: (a) peer-reviewed articles on stem cell transplantation for treating spinal cord injury that were published and indexed in the Web of Science; (b) type of articles: original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material, and news items; and (c) year of publication: 2002–2011. Exclusion criteria: (a) articles that required manual searching or telephone access; (b) documents that were not published in the public domain; and (c) a number of corrected papers from the total number of articles.MAIN OUTCOME MEASURES: (1) Annual publication output; (2) distribution according to country; (3) distribution according to institution; (4) distribution according to journals; (5) distribution according to funding agencies; and (6) top cited articles over the last 10 years.RESULTS: Bone marrow mesenchymal stem cells and embryonic stem cells have been widely used for treating spinal cord injury. In total, 191 studies of bone marrow mesenchymal stem cell transplantation and 236 studies of embryonic stem cell transplantation for treating spinal cord injury appeared in the Web of Science from 2002 to 2011, and almost half of which were derived from American or Japanese authors and institutes. The number of studies of stem cell transplantation for treating spinal cord injury has gradually increased over the past 10 years. Most papers on stem cell transplantation for treating spinal cord injury appeared in journals with a particular focus on stem cell research, such as Stem Cells and Cell Transplantation. Although umbilical cord blood stem cells and adipose

  1. Microencapsulation improves inhibitory effects of transplanted olfactory ensheathing cells on pain after sciatic nerve injury

    Directory of Open Access Journals (Sweden)

    Hao Zhao

    2015-01-01

    Full Text Available Olfactory bulb tissue transplantation inhibits P2X2/3 receptor-mediated neuropathic pain. However, the olfactory bulb has a complex cellular composition, and the mechanism underlying the action of purified transplanted olfactory ensheathing cells (OECs remains unclear. In the present study, we microencapsulated OECs in alginic acid, and transplanted free and microencapsulated OECs into the region surrounding the injured sciatic nerve in rat models of chronic constriction injury. We assessed mechanical nociception in the rat models 7 and 14 days after surgery by measuring paw withdrawal threshold, and examined P2X2/3 receptor expression in L 4-5 dorsal root ganglia using immunohistochemistry. Rats that received free and microencapsulated OEC transplants showed greater withdrawal thresholds than untreated model rats, and weaker P2X2/3 receptor immunoreactivity in dorsal root ganglia. At 14 days, paw withdrawal threshold was much higher in the microencapsulated OEC-treated animals. Our results confirm that microencapsulated OEC transplantation suppresses P2X2/3 receptor expression in L 4-5 dorsal root ganglia in rat models of neuropathic pain and reduces allodynia, and also suggest that transplantation of microencapsulated OECs is more effective than transplantation of free OECs for the treatment of neuropathic pain.

  2. Microencapsulation improves inhibitory effects of transplanted olfactory ensheathing cells on pain after sciatic nerve injury

    Institute of Scientific and Technical Information of China (English)

    Hao Zhao; Qing Li; Bao-lin Yang; Zeng-xu Liu; Qing Yu; Wen-jun Zhang; Keng Yuan; Hui-hong Zeng; Gao-chun Zhu; De-ming Liu

    2015-01-01

    Olfactory bulb tissue transplantation inhibits P2X2/3 receptor-mediated neuropathic pain. However, the olfactory bulb has a complex cellular composition, and the mechanism underlying the action of puriifed transplanted olfactory ensheathing cells (OECs) remains unclear. In the present study, we microencapsulated OECs in alginic acid, and transplanted free and microen-capsulated OECs into the region surrounding the injured sciatic nerve in rat models of chronic constriction injury. We assessed mechanical nociception in the rat models 7 and 14 days after surgery by measuring paw withdrawal threshold, and examined P2X2/3 receptor expression in L4–5 dorsal root ganglia using immunohistochemistry. Rats that received free and microencap-sulated OEC transplants showed greater withdrawal thresholds than untreated model rats, and weaker P2X2/3 receptor immunoreactivity in dorsal root ganglia. At 14 days, paw withdrawal threshold was much higher in the microencapsulated OEC-treated animals. Our results conifrm that microencapsulated OEC transplantation suppresses P2X2/3 receptor expression in L4–5 dorsal root ganglia in rat models of neuropathic pain and reduces allodynia, and also suggest that transplantation of microencapsulated OECs is more effective than transplantation of free OECs for the treatment of neuropathic pain.

  3. Magnetic Resonance Imaging of Transplanted Neural Stem Cells in Parkinson Disease Rats

    Institute of Scientific and Technical Information of China (English)

    YANG Lin; XIA Ying; ZHAO Hongyang; ZHAO Jiashan; ZHU Xianli

    2006-01-01

    In this study we implanted magnetically labeled neural stem cells (NSCs) in PD rats and then monitored their survival and migration in the host brain by magnetic resonance imaging (MRI).The mesencephalic NSCs were obtained from the brain of SD rats. Superparamagnetic iron oxide (SPIO) was transferred to NSCs by Lipofectamine transfection. Eighteen PD lesioned rats were selected for transplantation by evaluation of their rotational behavior in response to amphetamine and randomly assigned to 3 groups, i.e., sham group, PBS group and NSCs transplanted group, with 6 rats in each group. MR scanning was performed at 1, 2, 4, 6, 8 and 10 week(s) following transplantation.At the meantime, rotational behavior was assessed in each group. Our results showed that SPIO particles were clearly visible with Prissian blue staining in neurospheres and cells derived from NSCs.The rotational behavior of the NSCs transplanted group was remarkably improved compared with that of sham group and PBS group (P<0.05). In vivo MR tracking of NSCs showed that SPIO labeling led to a strong susceptibility change of signal 1 week after transplantation on T2 weighted images.And a large circular hypointense signal appeared in the transplanted area on T2* gradient echo images.Ten weeks following transplantation, the hypointense signal on T2 weighted and T2* gradient echo images was still displayed. It is concluded that SPIO particles could label NSCs effectively, and MRI detection of SPIO labeled cells is a promising method and novel approach to analyzing the NSCs following transplantation in the treatment of PD.

  4. Neuroprotective effects of human spinal cord-derived neural precursor cells after transplantation to the injured spinal cord.

    Science.gov (United States)

    Emgård, Mia; Piao, Jinghua; Aineskog, Helena; Liu, Jia; Calzarossa, Cinzia; Odeberg, Jenny; Holmberg, Lena; Samuelsson, Eva-Britt; Bezubik, Bartosz; Vincent, Per Henrik; Falci, Scott P; Seiger, Åke; Åkesson, Elisabet; Sundström, Erik

    2014-03-01

    To validate human neural precursor cells (NPCs) as potential donor cells for transplantation therapy after spinal cord injury (SCI), we investigated the effect of NPCs, transplanted as neurospheres, in two different rat SCI models. Human spinal cord-derived NPCs (SC-NPCs) transplanted 9 days after spinal contusion injury enhanced hindlimb recovery, assessed by the BBB locomotor test. In spinal compression injuries, SC-NPCs transplanted immediately or after 1 week, but not 7 weeks after injury, significantly improved hindlimb recovery compared to controls. We could not detect signs of mechanical allodynia in transplanted rats. Four months after transplantation, we found more human cells in the host spinal cord than were transplanted, irrespective of the time of transplantation. There was no focal tumor growth. In all groups the vast majority of NPCs differentiated into astrocytes. Importantly, the number of surviving rat spinal cord neurons was highest in groups transplanted acutely and subacutely, which also showed the best hindlimb function. This suggests that transplanted SC-NPCs improve the functional outcome by a neuroprotective effect. We conclude that SC-NPCs reliably enhance the functional outcome after SCI if transplanted acutely or subacutely, without causing allodynia. This therapeutic effect is mainly the consequence of a neuroprotective effect of the SC-NPCs.

  5. Chimeric Antigen Receptor T Cells and Hematopoietic Cell Transplantation: How Not to Put the CART Before the Horse.

    Science.gov (United States)

    Kenderian, Saad S; Porter, David L; Gill, Saar

    2017-02-01

    Hematopoietic cell transplantation (HCT) remains an important and potentially curative option for most hematologic malignancies. As a form of immunotherapy, allogeneic HCT (allo-HCT) offers the potential for durable remissions but is limited by transplantation- related morbidity and mortality owing to organ toxicity, infection, and graft-versus-host disease. The recent positive outcomes of chimeric antigen receptor T (CART) cell therapy in B cell malignancies may herald a paradigm shift in the management of these disorders and perhaps other hematologic malignancies as well. Clinical trials are now needed to address the relative roles of CART cells and HCT in the context of transplantation-eligible patients. In this review, we summarize the state of the art of the development of CART cell therapy for leukemia, lymphoma, and myeloma and discuss our perspective of how CART cell therapy can be applied in the context of HCT.

  6. Semaphorin 3A expression in spinal cord injured rats after olfactory ensheathing cell transplantation

    Institute of Scientific and Technical Information of China (English)

    Guoyu Wang; Xijing He; Puwei Yuan; Haopeng Li; Rui Chang

    2011-01-01

    Semaphorin 3A expression is thought to increase following spinal cord injury. The impact of olfactory ensheathing cell transplantation remains unclear. The current study demonstrated that spinal cord hemorrhage, edema, degeneration, necrosis, cyst formation, proliferation of glial cells, regeneration of nerve fibers and various pathological reactions occurred following a simple cross-section of spinal cord injury. Transplantation of olfactory ensheathing cells was found to significantly relieve the pathological reactions in the spinal cord described above, decrease the extent of necrosis in damaged neurons and nerve fibers, and downregulate semaphorin 3A expression in the injured zone. The results confirmed that olfactory ensheathing cell transplantation plays a protective role on the injured spinal cord by reducing the expression of semaphorin 3A.

  7. Intramyocardial transplantation of undifferentiated rat induced pluripotent stem cells causes tumorigenesis in the heart.

    Directory of Open Access Journals (Sweden)

    Yuzhen Zhang

    Full Text Available BACKGROUND: Induced pluripotent stem cells (iPSCs are a novel candidate for use in cardiac stem cell therapy. However, their intrinsic tumorigenicity requires further investigation prior to use in a clinical setting. In this study we investigated whether undifferentiated iPSCs are tumorigenic after intramyocardial transplantation into immunocompetent allogeneic recipients. METHODOLOGY/PRINCIPAL FINDINGS: We transplanted 2 × 10(4, 2 × 10(5, or 2 × 10(6 cells from the established rat iPSC line M13 intramyocardially into intact or infarcted hearts of immunocompetent allogeneic rats. Transplant duration was 2, 4, or 6 weeks. Histological examination with hematoxylin-eosin staining confirmed that undifferentiated rat iPSCs could generate heterogeneous tumors in both intracardiac and extracardiac sites. Furthermore, tumor incidence was independent of cell dose, transplant duration, and the presence or absence of myocardial infarction. CONCLUSIONS/SIGNIFICANCE: Our study demonstrates that allogeneic iPSC transplantation in the heart will likely result in in situ tumorigenesis, and that cells leaked from the beating heart are a potential source of tumor spread, underscoring the importance of evaluating the safety of future iPSC therapy for cardiac disease.

  8. Exploring a new therapy for diabetic polyneuropathy –the application of stem cell transplantation-

    Directory of Open Access Journals (Sweden)

    Hiroki eMizukami

    2014-04-01

    Full Text Available Diabetic polyneuropathy (DPN is the most common complication that emerges early in diabetic patients. Intervention with strict blood glucose control or treatment with aldose reductase inhibitor is reported to be effective in early stages of DPN. Curative treatment for overt or symptomatic DPN, however, has not been established, thus requiring much effort to explore a new therapy. Recent preclinical studies on the use of gene or cell therapy have provided promising results in the treatment of DPN. Of particular interest, induced pluripotent stem (iPS cells are introduced. In these studies, restoration of DPN was proposed to be attributed to either neurotrophic factors released from transplanted stem cells or differentiation of stem cells to substitute the damaged peripheral nerve. There are still several problems, however, that remain to be overcome, such as perturbed function, fragility or limited survival of transplanted cells in diabetes milieu and risk for malignant transformation of transplanted cells. Questions, which cell is the most appropriate as the source for cell therapy, or which site is the best for transplantation to obtain the most effective results, remain to be answered. In this communication, we overview the current status of preclinical studies on the cell therapy for DPN and discuss the future prospect.

  9. Decoy cells in the urine cytology of a renal transplant recipient: An immunohistochemical study

    Directory of Open Access Journals (Sweden)

    Pillai K

    2010-04-01

    Full Text Available Human polyoma virus causes renal dysfunction and graft loss as a result of tubulo-interstial nephritis in renal transplant recipients after reactivation of latent virus in renal epithelium. The infected cells in the urinary sediments are characterized by large homogenous inclusions, which may cause diagnostic error in urine cytology. The epithelial cells with polyoma viral inclusions in urine cytology specimens are termed Decoy cells to caution pathologists not to misdiagnose these cells as cancer cells. We present a case of polyoma viral changes detected the first time in our laboratory in the urine of a 46year old male who underwent renal transplantation six months back and followed by immunotherapy. Urine cytological examination showed decoy cells and subsequently revealed on histopathology. Immunoperoxidase staining for SV-40 LT antigen (LT ag, expression of proliferating cell nuclear antigen (PCNA, p53 and Rb genes were also studied in the tissue sections for further observation. The expression of SV40 LT ag was negative, while PCNA showed strong positivity; p53 and Rb were expressed moderately in the nuclei of cells in the tubules. The report of a case of decoy cells in the urine of a patient with renal transplantation focuses the importance of cytologic analysis of urine as a diagnostic tool for screening renal transplant recipients at risk of polyoma viral infection.

  10. Decoy cells in the urine cytology of a renal transplant recipient: an immunohistochemical study.

    Science.gov (United States)

    Pillai, K Raveendran; Jayasree, K; Pisharody, Ramdas; Abraham, Elizabeth K

    2010-01-01

    Human polyoma virus causes renal dysfunction and graft loss as a result of tubulo-interstial nephritis in renal transplant recipients after reactivation of latent virus in renal epithelium. The infected cells in the urinary sediments are characterized by large homogenous inclusions, which may cause diagnostic error in urine cytology. The epithelial cells with polyoma viral inclusions in urine cytology specimens are termed Decoy cells to caution pathologists not to misdiagnose these cells as cancer cells. We present a case of polyoma viral changes detected the first time in our laboratory in the urine of a 46year old male who underwent renal transplantation six months back and followed by immunotherapy. Urine cytological examination showed decoy cells and subsequently revealed on histopathology. Immunoperoxidase staining for SV-40 LT antigen (LT ag), expression of proliferating cell nuclear antigen (PCNA), p53 and Rb genes were also studied in the tissue sections for further observation. The expression of SV40 LT ag was negative, while PCNA showed strong positivity; p53 and Rb were expressed moderately in the nuclei of cells in the tubules. The report of a case of decoy cells in the urine of a patient with renal transplantation focuses the importance of cytologic analysis of urine as a diagnostic tool for screening renal transplant recipients at risk of polyoma viral infection.

  11. In Vivo Functional and Transcriptional Profiling of Bone Marrow Stem Cells after Transplantation into Ischemic Myocardium

    Science.gov (United States)

    Sheikh, Ahmad Y.; Huber, Bruno C.; Narsinh, Kazim H.; Spin, Joshua M.; van der Bogt, Koen; de Almeida, Patricia E.; Ransohoff, Katherine J.; Kraft, Daniel L.; Fajardo, Giovanni; Ardigo, Diego; Ransohoff, Julia; Bernstein, Daniel; Fischbein, Michael P.; Robbins, Robert C.; Wu, Joseph C.

    2011-01-01

    Objective Clinical trials of bone marrow-derived stem cell therapy for the heart have yielded variable results. The basic mechanism(s) that underlie their potential efficacy remains unknown. In the present study, we evaluate the survival kinetics, transcriptional response, and functional outcome of intramyocardial bone marrow mononuclear cell (BMMC) transplantation for cardiac repair in murine myocardial infarction model. Methods and Results We utilized molecular-genetic bioluminescence imaging and high throughput transcriptional profiling to evaluate the in vivo survival kinetics and gene expression changes of transplanted BMMCs after their engraftment into ischemic myocardium. Our results demonstrate short-lived survival of cells following transplant, with less than 1% of cells surviving by 6 weeks post-transplantation. Moreover, transcriptomic analysis of BMMCs revealed non-specific upregulation of various cell regulatory genes with a marked downregulation of cell differentiation and maturation pathways. BMMC therapy caused limited improvement of heart function as assessed by echocardiography, invasive hemodynamics, and positron emission tomography (PET). Histological evaluation of cell fate further confirmed findings of the in vivo cell tracking and transcriptomic analysis. Conclusions Collectively, these data suggest that BMMC therapy, in its present iteration, may be less efficacious than once thought. Additional refinement of existing cell delivery protocols should be considered to induce better therapeutic efficacy. PMID:22034515

  12. The biology of NK cells and their receptors affects clinical outcomes after hematopoietic cell transplantation (HCT).

    Science.gov (United States)

    Foley, Bree; Felices, Martin; Cichocki, Frank; Cooley, Sarah; Verneris, Michael R; Miller, Jeffrey S

    2014-03-01

    Natural killer (NK) cells were first identified for their capacity to reject bone marrow allografts in lethally irradiated mice without prior sensitization. Subsequently, human NK cells were detected and defined by their non-major histocompatibility complex (MHC)-restricted cytotoxicity toward transformed or virally infected target cells. Karre et al. later proposed 'the missing self hypothesis' to explain the mechanism by which self-tolerant cells could kill targets that had lost self MHC class I. Subsequently, the receptors that recognize MHC class I to mediate tolerance in the host were identified on NK cells. These class I-recognizing receptors contribute to the acquisition of function by a dynamic process known as NK cell education or licensing. In the past, NK cells were assumed to be short lived, but more recently NK cells have been shown to mediate immunologic memory to secondary exposures to cytomegalovirus infection. Because of their ability to lyse tumors with aberrant MHC class I expression and to produce cytokines and chemokines upon activation, NK cells may be primed by many stimuli, including viruses and inflammation, to contribute to a graft-versus-tumor effect. In addition, interactions with other immune cells support the therapeutic potential of NK cells to eradicate tumor and to enhance outcomes after hematopoietic cell transplantation.

  13. T-cell suicide gene therapy prompts thymic renewal in adults after hematopoietic stem cell transplantation.

    Science.gov (United States)

    Vago, Luca; Oliveira, Giacomo; Bondanza, Attilio; Noviello, Maddalena; Soldati, Corrado; Ghio, Domenico; Brigida, Immacolata; Greco, Raffaella; Lupo Stanghellini, Maria Teresa; Peccatori, Jacopo; Fracchia, Sergio; Del Fiacco, Matteo; Traversari, Catia; Aiuti, Alessandro; Del Maschio, Alessandro; Bordignon, Claudio; Ciceri, Fabio; Bonini, Chiara

    2012-08-30

    The genetic modification of T cells with a suicide gene grants a mechanism of control of adverse reactions, allowing safe infusion after partially incompatible hematopoietic stem cell transplantation (HSCT). In the TK007 clinical trial, 22 adults with hematologic malignancies experienced a rapid and sustained immune recovery after T cell-depleted HSCT and serial infusions of purified donor T cells expressing the HSV thymidine kinase suicide gene (TK+ cells). After a first wave of circulating TK+ cells, the majority of T cells supporting long-term immune reconstitution did not carry the suicide gene and displayed high numbers of naive lymphocytes, suggesting the thymus-dependent development of T cells, occurring only upon TK+ -cell engraftment. Accordingly, after the infusions, we documented an increase in circulating TCR excision circles and CD31+ recent thymic emigrants and a substantial expansion of the active thymic tissue as shown by chest tomography scans. Interestingly, a peak in the serum level of IL-7 was observed after each infusion of TK+ cells, anticipating the appearance of newly generated T cells. The results of the present study show that the infusion of genetically modified donor T cells after HSCT can drive the recovery of thymic activity in adults, leading to immune reconstitution.

  14. Autologous peripheral blood stem cell transplantation in patients with relapsed lymphoma results in accelerated haematopoietic reconstitution, improved quality of life and cost reduction compared with bone marrow transplantation : the Hovon 22 study

    NARCIS (Netherlands)

    Vellenga, E; van Agthoven, M; Croockewit, AJ; Verdonck, LF; Wijermans, PJ; van Oers, MHJ; Volkers, CP; van Imhoff, GW; Kingma, T; Uyl-de Groot, CA; Fibbe, WE

    2001-01-01

    The present study analysed whether autologous peripheral blood stem cell transplantation (PSCT) improves engraftment, quality of life and cost-effectiveness when compared with autologous bone marrow transplantation (ABMT). Relapsing progressive lymphoma patients (n = 204; non-Hodgkin's lymphoma n =

  15. Monitoring of Pathogen-Specific T-Cell Immune Reconstitution after Allogeneic Hematopoietic Stem Cell Transplantation

    Science.gov (United States)

    Fuji, Shigeo; Kapp, Markus; Einsele, Hermann

    2013-01-01

    The clinical outcome after allogeneic hematopoietic stem cell transplantation (HSCT) has been significantly improved during the last decades with regard to the reduction in organ failure, infection, and severe acute graft-versus-host disease. However, severe complications due to infectious diseases are still one of the major causes of morbidity and mortality after allogeneic HSCT, in particular in patients receiving haploidentical HSCT or cord blood transplant due to a slow and often incomplete immune reconstitution. In order to improve the immune control of pathogens without an increased risk of alloreactivity, adoptive immunotherapy using highly enriched pathogen-specific T cells offers a promising approach. In order to identify patients who are at high risk for infectious diseases, several monitoring assays have been developed with potential for the guidance of immunosuppressive drugs and adoptive immunotherapy in clinical practice. In this article, we aim to give a comprehensive overview regarding current developments of T-cell monitoring techniques focusing on T cells against viruses and fungi. In particular, we will focus on rather simple, fast, non-labor-intensive, cellular assays which could be integrated in routine clinical screening approaches. PMID:24062744

  16. Sirolimus for Refractory Autoimmune Hemolytic Anemia after Allogeneic Hematopoietic Stem Cell Transplantation: A Case Report and Literature Review of the Treatment of Post-Transplant Autoimmune Hemolytic Anemia.

    Science.gov (United States)

    Park, Jeong A; Lee, Hyun-Hee; Kwon, Hyun-Seop; Baik, Chung-Ryul; Song, Sae-Am; Lee, Jung Nye

    2016-01-01

    Autoimmune hemolytic anemia (AIHA) may occur after any type of allogeneic hematopoietic stem cell transplantation (HCT), even ABO-matched transplantation. It tends to be refractory to standard corticosteroid treatment and requires multiple transfusions. Though, there is no consensus regarding the optimal treatment for post-transplant severe AIHA. We present a pediatric patient with refractory AIHA after umbilical cord blood transplantation. She developed severe AIHA at 3months after transplantation and was unresponsive to multiple treatment modalities, including corticosteroids, intravenous immunoglobulin, plasma exchange and rituximab, resulting in persistent transfusion dependency. Sirolimus, a mammalian target of rapamycin inhibitor, was started on day 67 after the onset of AIHA, and this patient was successfully rescued without any complications. Sirolimus induces apoptosis in autoreactive lymphocytes, increases regulatory T cells and has been reported to have a positive effect on AIHA following solid organ transplantation (SOT). We reviewed the literature regarding post-transplant AIHA in the PubMed database and evaluated the treatment outcome of sirolimus in AIHA after SOT.

  17. Survival after T cell-depleted haploidentical stem cell transplantation is improved using the mother as donor.

    Science.gov (United States)

    Stern, Martin; Ruggeri, Loredana; Mancusi, Antonella; Bernardo, Maria Ester; de Angelis, Claudia; Bucher, Christoph; Locatelli, Franco; Aversa, Franco; Velardi, Andrea

    2008-10-01

    We hypothesized that transplacental leukocyte trafficking during pregnancy, which induces long-term, stable, reciprocal microchimerism in mother and child, might influence outcome of patients with acute leukemia given parental donor haploidentical hematopoietic stem cell transplantation (HSCT). We analyzed the outcome of 118 patients who received transplants for acute leukemia in 2 centers. Patients received highly T cell-depleted haploidentical grafts after myelo-ablative conditioning. Five-year event-free survival was better in patients who received transplants from the mother than from the father (50.6% +/- 7.6% vs 11.1% +/- 4.2%; P mother = 2.36; P = .003). In contrast, in a control cohort of patients who received transplants from haploidentical siblings, donor sex had no influence on outcome. Although obtained in a retrospective analysis, these data suggest that the mother of the patient should be preferred as donor for haploidentical HSCT.

  18. Dendritic Cells in Kidney Transplant Biopsy Samples Are Associated with T Cell Infiltration and Poor Allograft Survival.

    Science.gov (United States)

    Batal, Ibrahim; De Serres, Sacha A; Safa, Kassem; Bijol, Vanesa; Ueno, Takuya; Onozato, Maristela L; Iafrate, A John; Herter, Jan M; Lichtman, Andrew H; Mayadas, Tanya N; Guleria, Indira; Rennke, Helmut G; Najafian, Nader; Chandraker, Anil

    2015-12-01

    Progress in long-term renal allograft survival continues to lag behind the progress in short-term transplant outcomes. Dendritic cells are the most efficient antigen-presenting cells, but surprisingly little attention has been paid to their presence in transplanted kidneys. We used dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin as a marker of dendritic cells in 105 allograft biopsy samples from 105 kidney transplant recipients. High dendritic cell density was associated with poor allograft survival independent of clinical variables. Moreover, high dendritic cell density correlated with greater T cell proliferation and poor outcomes in patients with high total inflammation scores, including inflammation in areas of tubular atrophy. We then explored the association between dendritic cells and histologic variables associated with poor prognosis. Multivariate analysis revealed an independent association between the densities of dendritic cells and T cells. In biopsy samples with high dendritic cell density, electron microscopy showed direct physical contact between infiltrating lymphocytes and cells that have the ultrastructural morphologic characteristics of dendritic cells. The origin of graft dendritic cells was sought in nine sex-mismatched recipients using XY fluorescence in situ hybridization. Whereas donor dendritic cells predominated initially, the majority of dendritic cells in late allograft biopsy samples were of recipient origin. Our data highlight the prognostic value of dendritic cell density in allograft biopsy samples, suggest a new role for these cells in shaping graft inflammation, and provide a rationale for targeting dendritic cell recruitment to promote long-term allograft survival.

  19. Embryonic stem cells develop into hepatocytes after intrasplenic transplantation in CCl4-treated mice

    Institute of Scientific and Technical Information of China (English)

    Kei Moriya; Masahide Yoshikawa; Ko Saito; Yukiteru Ouji; Mariko Nishiofuku; Noriko Hayashi; Shigeaki Ishizaka; Hiroshi Fukui

    2007-01-01

    AIM: To transplant undifferentiated embryonic stem (ES) cells into the spleens of carbon tetrachloride (CCl4)-treated mice to determine their ability to differentiate into hepatocytes in the liver.METHODS: CCU, 0.5 mL/kg body weight, was injected into the peritoneum of C57BL/6 mice twice a week for 5 wk. In group 1 (n = 12), 1 x 105 undifferentiated ES cells (0.1 mL of 1 x 106/mL solution), genetically labeled with GFP, were transplanted into the spleens 1 d after the second injection. Group 2 mice (n = 12) were injected with 0.2 mL of saline twice a week, instead of CCU, and the same amount of ES cells was transplanted into the spleens. Group 3 mice (n = 6) were treated with CCU and injected with 0.1 mL of saline into the spleen, instead of ES cells. Histochemical analyses of the livers were performed on post-transplantation d (PD) 10, 20, and 30.RESULTS: Considerable numbers of GFP-immunopositive cells were found in the periportal regions in group 1 mice (CCl4-treated) on PD 10, however, not in those untreated with CCl4 (group 2). The GFP-positive cells were also immunopositive for albumin (ALB), alpha-1 antitrypsin, cytokeratin 18, and hepatocyte nuclear factor 4 alpha on PD 20. Interestingly, most of the GFP-positive cells were immunopositive for DLK, a hepatoblast marker, on PD 10. Although very few ES-derived cells were demonstrated immunohistologically in the livers of group 1 mice on PD 30, improvements in liver fibrosis were observed. Unexpectedly, liver tumor formation was not observed in any of the mice that received ES cell transplantation during the experimental period.CONCLUSION: Undifferentiated ES cells developed into hepatocyte-like cells with appropriate integration into tissue, without uncontrolled cell growth.

  20. Functional Reconstitution Of Natural Killer Cells In Allogeneic Hematopoietic Stem Cell Transplantation

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    Md Ashik eUllah

    2016-04-01

    Full Text Available Natural killer (NK cells are the first lymphocyte population to reconstitute following allogeneic hematopoietic stem cell transplantation (HSCT and are important in mediating immunity against both leukemia and pathogens. Although NK cell numbers generally reconstitute within a month, the acquisition of mature NK cell phenotype and full functional competency can take 6 months or more, and is influenced by graft composition, concurrent pharmacologic immunosuppression, graft-versus-host disease and other clinical factors. In addition, cytomegalovirus infection and reactivation have a dominant effect on NK cell memory imprinting following allogeneic HSCT just as it does in healthy individuals. Our understanding of NK cell education and licensing has evolved in the years since the ‘missing self’ hypothesis for NK-mediated graft-versus-leukemia effect was first put forward. For example, we now know that NK cell ‘re-education’ can occur, and that unlicensed NK cells can be more protective than licensed NK cells in certain settings, thus raising new questions about how best to harness graft-versus-leukemia effect. Here we review current understanding of the functional reconstitution of NK cells and NK cell education following allogeneic HSCT, highlighting a conceptual framework for future research.

  1. Circulating endocannabinoids during hematopoietic stem cell transplantation: A pilot study

    Directory of Open Access Journals (Sweden)

    Jennifer M. Knight

    2015-01-01

    Conclusions: The eCB signaling system may have alternative sources and regulatory mechanisms in addition to the immune system. Given the significant associations with inflammatory molecules and depressive symptoms in the peri-transplant period, it is important to better understand this system and its potential implications in the setting of complex and stressful medical procedures such as HCT.

  2. Glial cell transplants that are subsequently rejected can be used to influence regeneration of glial cell environments in the CNS.

    Science.gov (United States)

    Blakemore, W F; Crang, A J; Franklin, R J; Tang, K; Ryder, S

    1995-02-01

    Transplantation of glial cells into demyelinating lesions in CNS offers an experimental approach which allows investigation of the complex interactions that occur between CNS glia, Schwann cells, and axons during remyelination and repair. Earlier studies have shown that 1) transplanted astrocytes are able to prevent Schwann cells from participating in CNS remyelination, but that they are only able to do so with the cooperation of cells of the oligodendrocyte lineage, and 2) transplanted mouse oligodendrocytes can remyelinate rat axons provided their rejection is controlled by immunosuppression. On the basis of these observations, we have been able to prevent the Schwann cell remyelination that normally follows ethidium bromide demyelination in the rat spinal cord by co-transplanting isogeneic astrocytes with a potentially rejectable population of mouse oligodendrocyte lineage cells. Since male mouse cells were used it was possible to demonstrate their presence in immunosuppressed recipients using a mouse Y-chromosome probe by in situ hydridisation. When myelinating mouse cells were rejected by removal of immunosuppression, the demyelinated axons were remyelinated by host oligodendrocytes rather than Schwann cells, whose entry was prevented by the persistence of the transplanted isogeneic astrocytes. The oligodendrocyte remyelination was extensive and rapid, indicating that the inflammation associated with cell rejection did not impede repair. If this host oligodendrocyte remyelination was prevented by local X-irradiation, the lesion consisted of demyelinated axons surrounded by processes from the transplanted astrocytes. By this approach, it was possible to create an environment which resembled the chronic plaques of multiple sclerosis. Thus, these experiments demonstrate that in appropriate circumstances the temporary presence of a population of glial cells can alter the outcome of damage to the CNS.

  3. Sofosbuvir and Simeprevir Treatment of a Stem Cell Transplanted Teenager With Chronic Hepatitis C Infection.

    Science.gov (United States)

    Fischler, Björn; Priftakis, Peter; Sundin, Mikael

    2016-06-01

    There have been no previous reports on the use of interferon-free combinations in pediatric patients with chronic hepatitis C infection. An infected adolescent with severe sickle cell disease underwent stem cell transplantation and subsequent treatment with sofosbuvir and simeprevir during ongoing immunosuppression. Despite the emergence of peripheral edema as a side effect, treatment was continued with sustained antiviral response.

  4. Neuro-immune interactions of neural stem cell transplants: from animal disease models to human trials.

    Science.gov (United States)

    Giusto, Elena; Donegà, Matteo; Cossetti, Chiara; Pluchino, Stefano

    2014-10-01

    Stem cell technology is a promising branch of regenerative medicine that is aimed at developing new approaches for the treatment of severely debilitating human diseases, including those affecting the central nervous system (CNS). Despite the increasing understanding of the mechanisms governing their biology, the application of stem cell therapeutics remains challenging. The initial idea that stem cell transplants work in vivo via the replacement of endogenous cells lost or damaged owing to disease has been challenged by accumulating evidence of their therapeutic plasticity. This new concept covers the remarkable immune regulatory and tissue trophic effects that transplanted stem cells exert at the level of the neural microenvironment to promote tissue healing via combination of immune modulatory and tissue protective actions, while retaining predominantly undifferentiated features. Among a number of promising candidate stem cell sources, neural stem/precursor cells (NPCs) are under extensive investigation with regard to their therapeutic plasticity after transplantation. The significant impact in vivo of experimental NPC therapies in animal models of inflammatory CNS diseases has raised great expectations that these stem cells, or the manipulation of the mechanisms behind their therapeutic impact, could soon be translated to human studies. This review aims to provide an update on the most recent evidence of therapeutically-relevant neuro-immune interactions following NPC transplants in animal models of multiple sclerosis, cerebral stroke and traumas of the spinal cord, and consideration of the forthcoming challenges related to the early translation of some of these exciting experimental outcomes into clinical medicines.

  5. Bone marrow-derived hematopoietic stem and progenitor cells infiltrate allogeneic and syngeneic transplants.

    Science.gov (United States)

    Fan, Z; Enjoji, K; Tigges, J C; Toxavidis, V; Tchipashivili, V; Gong, W; Strom, T B; Koulmanda, M

    2014-12-01

    Lineage (CD3e, CD11b, GR1, B220 and Ly-76) negative hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) infiltrate islet allografts within 24 h posttransplantation. In fact, lineage(negative) Sca-1(+) cKit(+) ("LSK") cells, a classic signature for HSCs, were also detected among these graft infiltrating cells. Lineage negative graft infiltrating cells are functionally multi-potential as determined by a standard competitive bone marrow transplant (BMT) assay. By 3 months post-BMT, both CD45.1 congenic, lineage negative HSCs/HPCs and classic "LSK" HSCs purified from islet allograft infiltrating cells, differentiate and repopulate multiple mature blood cell phenotypes in peripheral blood, lymph nodes, spleen, bone marrow and thymus of CD45.2 hosts. Interestingly, "LSK" HSCs also rapidly infiltrate syngeneic islet transplants as well as allogeneic cardiac transplants and sham surgery sites. It seems likely that an inflammatory response, not an adaptive immune response to allo-antigen, is responsible for the rapid infiltration of islet and cardiac transplants by biologically active HSCs/HPCs. The pattern of hematopoietic differentiation obtained from graft infiltrating HSCs/HPCs, cells that are recovered from inflammatory sites, as noted in the competitive BMT assay, is not precisely the same as that of intramedullary HSCs. This does not refute the obvious multi-lineage potential of graft infiltrating HSCs/HPCs.

  6. Non-human primate regulatory T cells: Current biology and implications for transplantation

    NARCIS (Netherlands)

    E.M. Dons (Eefje); G. Raimondi (Giorgio); D.K.C. Cooper (David); A.W. Thomson (Angus)

    2010-01-01

    textabstractRegulatory T cells (Treg) offer potential for improving long-term outcomes in cell and organ transplantation. The non-human primate model is a valuable resource for addressing issues concerning the transfer of Treg therapy to the clinic. Herein, we discuss the properties of non-human pri

  7. Advances in unrelated and alternative donor hematopoietic cell transplantation for nonmalignant disorders

    NARCIS (Netherlands)

    Shenoy, Shalini; Boelens, Jaap J.

    2015-01-01

    PURPOSE OF REVIEW: The role of hematopoietic cell transplantation in non-malignant disorders has increased exponentially with the recognition that multiple diseases can be controlled or cured if engrafted with donor-derived cells. This review provides an overview of advances made in alternative dono

  8. 75 FR 62843 - Advisory Council on Blood Stem Cell Transplantation; Notice of Meeting

    Science.gov (United States)

    2010-10-13

    ... HUMAN SERVICES Health Resources and Services Administration Advisory Council on Blood Stem Cell... Act, as amended) the Advisory Council on Blood Stem Cell Transplantation (ACBSCT) advises the.... L. 92-463), notice is hereby given of the following meeting: Name: Advisory Council on Blood...

  9. Evaluation of human hemopoietic stem cell assays for transplantation and gene therapy

    NARCIS (Netherlands)

    P.B. van Hennik

    2001-01-01

    textabstractHemopoietic stem cell transplantation has become an important treatment modality for various hematological and non-hematological diseases, e.g. leukemia, lymphoma, congenital immunodeficiencies, autoimmune disease as well as solid tumors. In addition, the use of hemopoietic stem cell tra

  10. Improvement of Thymopoiesis after Hematopoietic Stem Cell Transplantation by Cytokines: Translational studies in experimental animal models

    NARCIS (Netherlands)

    E-J. Wils (Evert-Jan)

    2011-01-01

    textabstractAllogeneic hematopoietic stem cell transplantation (AlloHSCT) is a powerful treatment modality that is frequently applied as part of treatment of hematological malignancies, aplastic anemia and inborn errors of hematopoietic progenitor cells. A major drawback of alloHSCT is the treatment

  11. Cellular islet autoimmunity associates with clinical outcome of islet cell transplantation.

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    Volkert A L Huurman

    Full Text Available BACKGROUND: Islet cell transplantation can cure type 1 diabetes (T1D, but only a minority of recipients remains insulin-independent in the following years. We tested the hypothesis that allograft rejection and recurrent autoimmunity contribute to this progressive loss of islet allograft function. METHODOLOGY/PRINCIPAL FINDINGS: Twenty-one T1D patients received cultured islet cell grafts prepared from multiple donors and transplanted under anti-thymocyte globulin (ATG induction and tacrolimus plus mycophenolate mofetil (MMF maintenance immunosuppression. Immunity against auto- and alloantigens was measured before and during one year after transplantation. Cellular auto- and alloreactivity was assessed by lymphocyte stimulation tests against autoantigens and cytotoxic T lymphocyte precursor assays, respectively. Humoral reactivity was measured by auto- and alloantibodies. Clinical outcome parameters--including time until insulin independence, insulin independence at one year, and C-peptide levels over one year--remained blinded until their correlation with immunological parameters. All patients showed significant improvement of metabolic control and 13 out of 21 became insulin-independent. Multivariate analyses showed that presence of cellular autoimmunity before and after transplantation is associated with delayed insulin-independence (p = 0.001 and p = 0.01, respectively and lower circulating C-peptide levels during the first year after transplantation (p = 0.002 and p = 0.02, respectively. Seven out of eight patients without pre-existent T-cell autoreactivity became insulin-independent, versus none of the four patients reactive to both islet autoantigens GAD and IA-2 before transplantation. Autoantibody levels and cellular alloreactivity had no significant association with outcome. CONCLUSIONS/SIGNIFICANCE: In this cohort study, cellular islet-specific autoimmunity associates with clinical outcome of islet cell transplantation under ATG

  12. Transplantation of olfactory ensheathing cells for promoting regeneration following spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    Kaijun Liu

    2007-01-01

    OBJECTIVE: To investigate the status of olfactory ensheathing cells (OECs) transplantation in facilitating the regeneration of spinal cord injury.DATA SOURCES: Articles about OECs transplantation in treating spinal cord injury were searched in Pubmed database published in English from January 1981 to December 2005 by using the keywords of "olfactory ensheathing cells, transplantation, spinal cord injury".STUDY SELECTION: The data were checked primarily, literatures related to OECs transplantation and the regeneration of spinal cord injury were selected, whereas the repetitive studies and reviews were excluded.DATA EXTRACTION: Totally 43 articles about OECs transplantation and the regeneration and repair of spinal cord injury were collected, and the repetitive ones were excluded.DATA SYNTHESIS: There were 35 articles accorded with the criteria. OECs are the olfactory ensheathing glias isolated from olfactory bulb and olfactory nerve tissue. OECs have the characters of both Schwann cells in central nervous system and peripheral astrocytes. The transplanted OECs can migrate in the damaged spinal cord of host, can induce and support the regeneration, growth and extension of damaged neuritis.Besides, transgenic technique can enable it to carry some exogenous genes that promote neuronal regeneration, and express some molecules that can facilitate neural regeneration, so as to ameliorate the internal environment of nerve injury, induce the regeneration of damaged spinal cord neurons, which can stimulate the regeneration potential of the damaged spinal cord to reach the purpose of spinal cord regeneration and functional recovery.CONCLUSION: OECs are the glial cells with the energy for growth at mature phase, they can myelinize axons, secrete various biological nutrition factors, and then protect and support neurons, also facilitate neural regeneration. OECs have been successfully isolated from nasal olfactory mucosa and olfactory nerve.Therefore, autologous transplantation

  13. Vascular smooth muscle cell apoptosis promotes transplant arteriosclerosis through inducing the production of SDF-1α.

    Science.gov (United States)

    Li, J; Liu, S; Li, W; Hu, S; Xiong, J; Shu, X; Hu, Q; Zheng, Q; Song, Z

    2012-08-01

    Transplant arteriosclerosis is a leading cause of late allograft loss. Medial smooth muscle cell (SMC) apoptosis is considered to be an important event in transplant arteriosclerosis. However, the precise contribution of medial SMC apoptosis to transplant arteriosclerosis and the underlying mechanisms remain unclear. We transferred wild-type p53 to induce apoptosis of cultured SMCs. We found that apoptosis induces the production of SDF-1α from apoptotic and neighboring viable cells, resulting in increased SDF-1α in the culture media. Conditioned media from Ltv-p53-transferred SMCs activated PI3K/Akt/mTOR and MAPK/Erk signaling in a SDF-1α-dependent manner and thereby promoted mesenchymal stem cell (MSC) migration and proliferation. In a rat aorta transplantation model, lentivirus-mediated BclxL transfer selectively inhibits medial SMC apoptosis in aortic allografts, resulting in a remarkable decrease of SDF-1α both in allograft media and in blood plasma, associated with diminished recruitment of CD90(+)CD105(+) double-positive cells and impaired neointimal formation. Systemic administration of rapamycin or PD98059 also attenuated MSC recruitment and neointimal formation in the aortic allografts. These results suggest that medial SMC apoptosis is critical for the development of transplant arteriosclerosis through inducing SDF-1α production and that MSC recruitment represents a major component of vascular remodeling, constituting a relevant target and mechanism for therapeutic interventions.

  14. Secondary monoclonal gammopathy of undetermined significance after allogeneic stem cell transplantation in multiple myeloma.

    Science.gov (United States)

    Schmitz, Marian F; Otten, Henny G; Franssen, Laurens E; van Dorp, Suzanne; Strooisma, Theo; Lokhorst, Henk M; van de Donk, Niels W C J

    2014-12-01

    In the course of multiple myeloma, patients may develop a M-protein band different from the original: secondary monoclonal gammopathy of undetermined significance. In this retrospective single center analysis, we describe the occurrence and clinical relevance of secondary monoclonal gammopathy of undetermined significance after allogeneic stem cell transplantation (post-transplant monoclonal gammopathy of undetermined significance). A total of 138 patients who had undergone 139 allogeneic stem cell transplantations (39.6% in the upfront setting and 60.4% for relapsed multiple myeloma) were included in the study. Sixty-seven (48.2%) patients developed secondary monoclonal gammopathy of undetermined significance, after a median latency of 6.9 months. Secondary monoclonal gammopathy of undetermined significance occurred more often in patients who achieved at least very good partial response after allogeneic stem cell transplantation, compared to partial response or less (54.8% vs. 26.5%; P=0.005). The incidence was also higher in the upfront setting as compared to relapsed disease, or with a sibling donor compared to matched unrelated donor, but less often after T-cell depletion. Importantly, development of post-transplant monoclonal gammopathy of undetermined significance as a time-dependent variable independently predicted for superior progression-free and overall survival (median progression-free survival 37.5 vs. 6.3 months, Pundetermined significance should not be confused with relapse or progression of disease. (Trial registered with trialregister.nl; HOVON 108: NTR 2958.).

  15. The need for xenotransplantation as a source of organs and cells for clinical transplantation.

    Science.gov (United States)

    Ekser, Burcin; Cooper, David K C; Tector, A Joseph

    2015-11-01

    The limited availability of deceased human organs and cells for the purposes of clinical transplantation remains critical worldwide. Despite the increasing utilization of 'high-risk', 'marginal', or 'extended criteria' deceased donors, in the U.S. each day 30 patients either die or are removed from the waiting list because they become too sick to undergo organ transplantation. In certain other countries, where there is cultural resistance to deceased donation, e.g., Japan, the increased utilization of living donors, e.g., of a single kidney or partial liver, only very partially addresses the organ shortage. For transplants of tissues and cells, e.g., pancreatic islet transplantation for patients with diabetes, and corneal transplantation for patients with corneal blindness (whose numbers worldwide are potentially in the millions), allotransplantation will never prove a sufficient source. There is an urgent need for an alternative source of organs and cells. The pig could prove to be a satisfactory source, and clinical xenotransplantation using pig organs or cells, particularly with the advantages provided by genetic engineering to provide resistance to the human immune response, may resolve the organ shortage. The physiologic compatibilities and incompatibilities of the pig and the human are briefly reviewed.

  16. Stem cell transplantation for treating stroke:status, trends and development

    Institute of Scientific and Technical Information of China (English)

    Wenxin Huo; Xiaoyang Liu; Cheng Tan; Yingying Han; Chunyang Kang; Wei Quan; Jiajun Chen

    2014-01-01

    The developing approaches of thrombolytic therapy, endovascular treatment, neuroprotective therapy, and stem cell therapy have enabled breakthroughs in stroke treatment. In this study, we summarize and analyze trends and progress in stem cell transplantation for stroke treatment by retrieval of literature from Thomson Reuters Web of Science database, the NIH Clinical Trial Planning Grant Program, and Clinical Trials Registration Center in North America. In the last 10 years, there has been an increasing number of published articles on stem cell transplantation for stroke treatment. In particular, research from the USA and China has focused on stem cell transplantation. A total of 2,167 articles addressing stem cell transplantation for stroke treatment from 2004 to 2013 were retrieved from the Thomson Reuters Web of Science database. The ma-jority of these articles were from the USA (854, 39.4%), with the journal Stroke publishing the most articles (145, 6.7%). Of the published articles, 143 were funded by the National Institutes of Health (accounting for 6.6%of total publications), and 91 by the National Natural Science Foundation of China. Between 2013 and 2014, the National Institutes of Health provided ifnan-cial support ($130 million subsidy) for 329 research projects on stroke therapy using stem cell transplantation. In 2014, 215 new projects were approved, receiving grants of up to$70,440,000. Ninety clinical trials focusing on stem cell transplantation for stroke were registered in the Clin-ical Trial Registration Center in North America, with 40 trials registered in the USA (ranked ifrst place). China had the maximum number of registered research or clinical trials (10 projects).

  17. A CLINICAL STUDY OF LIMBAL STEM CELL TRANSPLANTATION IN VARIOUS OCULAR SURFACE DISORDERS

    Directory of Open Access Journals (Sweden)

    Rashmi

    2015-10-01

    Full Text Available AIMS: The purpose of this study is to evaluate the various causes of limbal stem cell deficiency, to assess signs and symptoms in ocular surface disorder and improvement following stem cell transplantation, to carry out limbal stem cell transplantation in various ocular surface disorders and to assess various intraoperative and postoperative complications following stem cell transplantation. METHODS: This study included 40 cases of ocular surface disorders treated with limbal autograft transplantation. Patients were recorded in a predesigned proforma, including the detailed history and complete ophthalmological examination. All cases of ocular surface disorders were treated with conjunctivo-limbal autograft transplantation under peribulbar and facial anaesthesia. RESULT: Maximum number of patients belong to age group 30-40 years. Males were more commonly affected by ocular surface disorders than females. (1.8:1. various causes of limbal stem cell deficiency were reviewed. The most common etiology associated with limbal stem cell deficiency was pterygia (60% followed by vascularised leucomatous corneal opacity (20%, chemical burns (15% and epitheliopathy (5%. Most common symptoms reported by patients were redness (100%, foreign body sensation (90%, watering (85% and photophobia (50%. Most common signs found were conjunctival congestion (90%, corneal vascularization (70%, conjunctivalisation (70% and epithelial defects (30%. 72.5% of patients reported increased ocular comfort. Postoperative incidence of redness was reduced from 90% to 20%, watering from 85% to 15% and photophobia from 50% to 25%. Improvement in signs was noted as decrease in conjunctival congestion from 90% to 22.2%, vascularisation from 70% to 35%, conjunctivalisation from 70% to 21.5% and epithelial defects from 30% to 16.6%. CONCLUSIONS: Use of autologous limbal transplantation with corneal and conjunctival tissue as a vehicle was useful for ocular surface reconstruction in

  18. Matrix elasticity of void-forming hydrogels controls transplanted-stem-cell-mediated bone formation

    Science.gov (United States)

    Huebsch, Nathaniel; Lippens, Evi; Lee, Kangwon; Mehta, Manav; Koshy, Sandeep T.; Darnell, Max C.; Desai, Rajiv M.; Madl, Christopher M.; Xu, Maria; Zhao, Xuanhe; Chaudhuri, Ovijit; Verbeke, Catia; Kim, Woo Seob; Alim, Karen; Mammoto, Akiko; Ingber, Donald E.; Duda, Georg N.; Mooney, David J.

    2015-12-01

    The effectiveness of stem cell therapies has been hampered by cell death and limited control over fate. These problems can be partially circumvented by using macroporous biomaterials that improve the survival of transplanted stem cells and provide molecular cues to direct cell phenotype. Stem cell behaviour can also be controlled in vitro by manipulating the elasticity of both porous and non-porous materials, yet translation to therapeutic processes in vivo remains elusive. Here, by developing injectable, void-forming hydrogels that decouple pore formation from elasticity, we show that mesenchymal stem cell (MSC) osteogenesis in vitro, and cell deployment in vitro and in vivo, can be controlled by modifying, respectively, the hydrogel’s elastic modulus or its chemistry. When the hydrogels were used to transplant MSCs, the hydrogel’s elasticity regulated bone regeneration, with optimal bone formation at 60 kPa. Our findings show that biophysical cues can be harnessed to direct therapeutic stem cell behaviours in situ.

  19. Increasing magnetite contents of polymeric magnetic particles dramatically improves labeling of neural stem cell transplant populations.

    Science.gov (United States)

    Adams, Christopher F; Rai, Ahmad; Sneddon, Gregor; Yiu, Humphrey H P; Polyak, Boris; Chari, Divya M

    2015-01-01

    Safe and efficient delivery of therapeutic cells to sites of injury/disease in the central nervous system is a key goal for the translation of clinical cell transplantation therapies. Recently, 'magnetic cell localization strategies' have emerged as a promising and safe approach for targeted delivery of magnetic particle (MP) labeled stem cells to pathology sites. For neuroregenerative applications, this approach is limited by the lack of available neurocompatible MPs, and low cell labeling achieved in neural stem/precursor populations. We demonstrate that high magnetite content, self-sedimenting polymeric MPs [unfunctionalized poly(lactic acid) coated, without a transfecting component] achieve efficient labeling (≥90%) of primary neural stem cells (NSCs)-a 'hard-to-label' transplant population of major clinical relevance. Our protocols showed high safety with respect to key stem cell regenerative parameters. Critically, labeled cells were effectively localized in an in vitro flow system by magnetic force highlighting the translational potential of the methods used.

  20. Transplantation and stem cell research in neurosciences: where does India stand?

    Science.gov (United States)

    Tandon, Prakash N

    2009-01-01

    The nearly absent ability of the neurons to regenerate or multiply has prompted neuroscientists to search for the mean to replace damaged or dead cells. The failed attempts using adult tissue, initiated nearly a century ago, ultimately brought rays of hope when developing fetal neurons were used for transplantation in 1970s. The initial excitement was tempered by limited success and ethical issues. But these efforts unequivocally established the feasibility of successful neural transplantation provided appropriate tissue was available. The ability to derive embryonic stem cells with their totipotent potential by Thomson in 1998 rekindled the interest in their use for replacement therapy for damaged brain tissue. The present review surveys the current status of this promising field of stem cell research especially in respect to their therapeutic potentials for purposes of neural transplantation. A brief account is provided of the ongoing Indian efforts in this direction.

  1. Hyperbaric oxygen therapy combined with Schwann cell transplantation promotes spinal cord injury recovery

    Directory of Open Access Journals (Sweden)

    Chuan-gang Peng

    2015-01-01

    Full Text Available Schwann cell transplantation and hyperbaric oxygen therapy each promote recovery from spinal cord injury, but it remains unclear whether their combination improves therapeutic results more than monotherapy. To investigate this, we used Schwann cell transplantation via the tail vein, hyperbaric oxygen therapy, or their combination, in rat models of spinal cord contusion injury. The combined treatment was more effective in improving hindlimb motor function than either treatment alone; injured spinal tissue showed a greater number of neurite-like structures in the injured spinal tissue, somatosensory and motor evoked potential latencies were notably shorter, and their amplitudes greater, after combination therapy than after monotherapy. These findings indicate that Schwann cell transplantation combined with hyperbaric oxygen therapy is more effective than either treatment alone in promoting the recovery of spinal cord in rats after injury.

  2. UPDATE ON THE ROLE OF AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION IN MULTIPLE MYELOMA

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    Patrizia Tosi

    2012-11-01

    Full Text Available Autologous stem cell transplantation is considered the standard of care for multiple myeloma patients aged < 65 years with no relevant comorbidities. The addition of drugs acting both on bone marrow microenvironment and on neoplastic plasma cells has significantly increased the proportion of patients achieving a complete remission after induction therapy, and these results are mantained after high-dose melphalan, leading to a prolonged disease control. Studies are being carried out in order to evaluate whether short term consolidation or long-term maintenance therapy can result into disease eradication at the molecular level thus increasing also patients survival. The efficacy of these new drugs has raised the issue of deferring the transplant after achivng a second response upon relapse. Another controversial point is the optimal treatment strategy for high-risk patients, that do not benefit from autologous stem cell transplantation and for whom the efficacy of new drugs is still matter of debate.

  3. Hematopoietic stem cell transplantation monitoring in childhood. Hematological diseases in Serbia: STR-PCR techniques

    Directory of Open Access Journals (Sweden)

    Krstić Aleksandra D.

    2007-01-01

    Full Text Available Hematopoietic stem cell transplantation (HSCT is a very successful method of treatment for children with different aquired or inborn diseases. The main goal of post-transplantation chimerism monitoring in HSCT is to predict negative events (such as disease relapse and graft rejection, in order to intervene with appropriate therapy and improve the probability of long-term DFS (disease free survival. In this context, by quantifying the relative amounts of donor and recipient cells present in the peripheral blood sample, it can be determined if engraftment has taken place at all, or if full or mixed chimerism exists. In a group of patients who underwent hematopoietic stem cell transplantation at the Mother and Child Health Care Institute, we decided to use standard human identfication tests based on multiplex PCR analyses of short tandem repeats (STRs, as they are highly informative, sensitive, and fast and therefore represent an optimal methodological approach to engraftment analysis.

  4. High-Dose Y-90-Ibritumomab Tiuxetan Added to Reduced-Intensity Allogeneic Stem Cell Transplant Regimen for Relapsed or Refractory Aggressive B-Cell Lymphoma

    Science.gov (United States)

    2016-07-08

    Post-Transplant Lymphoproliferative Disorder; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Burkitt Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma

  5. In utero depletion of fetal hematopoietic stem cells improves engraftment after neonatal transplantation in mice.

    Science.gov (United States)

    Derderian, S Christopher; Togarrati, P Priya; King, Charmin; Moradi, Patriss W; Reynaud, Damien; Czechowicz, Agnieszka; Weissman, Irving L; MacKenzie, Tippi C

    2014-08-07

    Although in utero hematopoietic cell transplantation is a promising strategy to treat congenital hematopoietic disorders, levels of engraftment have not been therapeutic for diseases in which donor cells have no survival advantage. We used an antibody against the murine c-Kit receptor (ACK2) to deplete fetal host hematopoietic stem cells (HSCs) and increase space within the hematopoietic niche for donor cell engraftment. Fetal mice were injected with ACK2 on embryonic days 13.5 to 14.5 and surviving pups were transplanted with congenic hematopoietic cells on day of life 1. Low-dose ACK2 treatment effectively depleted HSCs within the bone marrow with minimal toxicity and the antibody was cleared from the serum before the neonatal transplantation. Chimerism levels were significantly higher in treated pups than in controls; both myeloid and lymphoid cell chimerism increased because of higher engraftment of HSCs in the bone marrow. To test the strategy of repeated HSC depletion and transplantation, some mice were treated with ACK2 postnatally, but the increase in engraftment was lower than that seen with prenatal treatment. We demonstrate a successful fetal conditioning strategy associated with minimal toxicity. Such strategies could be used to achieve clinically relevant levels of engraftment to treat congenital stem cell disorders.

  6. Transplantation of placenta-derived mesenchymal stem cell-induced neural stem cells to treat spinal cord injur y

    Institute of Scientific and Technical Information of China (English)

    Zhi Li; Wei Zhao; Wei Liu; Ye Zhou; Jingqiao Jia; Lifeng Yang

    2014-01-01

    Because of their strong proliferative capacity and multi-potency, placenta-derived mesenchymal stem cells have gained interest as a cell source in the ifeld of nerve damage repair. In the present study, human placenta-derived mesenchymal stem cells were induced to differentiate into neural stem cells, which were then transplanted into the spinal cord after local spinal cord injury in rats. The motor functional recovery and pathological changes in the injured spinal cord were observed for 3 successive weeks. The results showed that human placenta-derived mesenchymal stem cells can differentiate into neuron-like cells and that induced neural stem cells contribute to the resto-ration of injured spinal cord without causing transplant rejection. Thus, these cells promote the recovery of motor and sensory functions in a rat model of spinal cord injury. Therefore, human placenta-derived mesenchymal stem cells may be useful as seed cells during the repair of spinal cord injury.

  7. Fatal EBV-related post-transplant lymphoproliferative disorder (LPD) after matched related donor nonmyeloablative peripheral blood progenitor cell transplant.

    Science.gov (United States)

    Zamkoff, K W; Bergman, S; Beaty, M W; Buss, D H; Pettenati, M J; Hurd, D D

    2003-02-01

    A 39-year-old male underwent a nonmyeloablative stem cell transplant (NMAPBPCT) from his HLA-matched sister for recurrent anaplastic large cell lymphoma in CR-2, receiving fludarabine, cyclophosphamide, and rabbit antithymocyte globulin for the preparative therapy. The patient was readmitted on day+33 for persistent culture-negative fevers. He rapidly developed marked elevations of alkaline phosphatase and bilirubin. Liver biopsy showed a periportal infiltrate of large immunoblastic appearing cells. The tumor cells did not stain for CD3/CD20/CD30 and alk protein, but did stain for CD79a/LCA and CD43. In situ hybridization for Epstein-Barr virus (EBV) RNA (EBER 1) was strongly positive in the periportal infiltrating lymphocytes. Fluorescence in situ hybridization (FISH) studies revealed female (XX) cells in the tumor cells and male (XY) in the surrounding hepatic parenchymal cells. The patient developed severe lactic acidosis, oliguric renal failure and expired on day+44. Both donor and patient had positive IgG serologies for EBV VCA and EBNA pretransplant. The donor also had a positive IgM titer for EBV VCA in the pretransplant specimen. The LPD may have been related to the intense immunosuppression of the preparative therapy and the presence of recent EBV infection in the donor.

  8. Transplantation of primary cultured embryonic mesencephalic neural precursor cells for treating Parkinsonian rats

    Institute of Scientific and Technical Information of China (English)

    Li Fei; Chengchuan Jiang; Linyin Feng; Yaodong Ji; Zhongliang Ding

    2006-01-01

    BACKGROUND: Choosing proper donor cells is one of keys in experimental and clinical studies on cell replacement therapy (CRT) for treating Parkinson disease (PD). Embryonic mesencephalic precursor cells (MPCs) can stably differentiate into dopaminergic neuron after in vitro proliferated culture. As compared with embryonic stem cell and neural stem cell strains, cell composition of embryonic MPCs after primary culture is also the most close to that of embryonic mesencephalic ventral cell suspension without proliferated culture. Successful experience accumulated in the latter suggests that primary cultured embryonic MPCs might be the most potential donor cells in clinical application with CRT for treating PD so far.OBJECTIVE: To investigate the feasibility of primary cultured embryonic precursor cells cultured primarily as donor cells in CRT for treating PD in rats.DESIGN: A randomized and controlled trial taking SD rats as experimental animals.SETTING: Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University.MATERIALS: This experiment was carried out at the Institute of Neuroscience, Shanghai Institute for Biological Science, Chinese Academy of Sciences from July 2003 to June 2004. Totally 26 female SD rats,with body mass of 200 to 220 g, were provided by Shanghai Experimental Animal Center of Chinese Academy of Sciences.METHODS: Stereotaxic injection of 6-hydroxydopamine into the medial forebrain bundle were perfored to develop PD model rat. Among 26 SD rats, 20 rats achieved a more than 5 turns/min in apomorphine induced rotation test, reaching the standard of PD model rats. Immunohistochemical detection was performed on 1out of 20 model rats after execution, and the other 19 rats were randomly divided into control group (n=5),sham transplantation group (n=5)and cell grafted group (n=9). Primary cultured E12 MPC cell suspension (1.2×1011 L-1)were used as donor cells. 4 μL primary cultured E12 MPC cell suspension prepared freshly was injected

  9. Chemical injury treated with autologous limbal epithelial stem cell transplantation and subconjunctival bevacizumab

    Directory of Open Access Journals (Sweden)

    Cavallini GM

    2014-08-01

    Full Text Available Gian Maria Cavallini,1 Graziella Pellegrini,2 Veronica Volante,1 Pietro Ducange,1 Michele De Maria,1 Giulio Torlai,1 Caterina Benatti,1 Matteo Forlini1 1Institute of Ophthalmology, 2Centre for Regenerative Medicine “Stefano Ferrari”, University of Modena e Reggio Emilia, Modena, Italy Background: Limbal stem cell (LSC deficiency leads to corneal opacity due to a conjunctivalization of the corneal surface. LSC transplantation, which can be followed by corneal keratoplasty, is an effective procedure to restore corneal transparency; however, a common cause of failure of this procedure is neovascularization (NV.Methods: A 59-year-old man with a 21-year history of a corneal chemical burn caused by phosphoric acid in his left eye was examined. He presented with unilateral total LSC deficiency with severe conjunctivalization and a corrected distance visual acuity that was limited to hand motion.Results: We reported the short-term in vivo efficacy of subconjunctival bevacizumab for progressive corneal NV in a patient with LSC deficiency that underwent LSC transplantation. Four months after autologous LSC transplantation and 1 month after the second subconjunctival bevacizumab injection, the patient’s corrected distance visual acuity was 1/10.Conclusion: Subconjunctival injection of bevacizumab can reduce the corneal NV, reducing conjunctival inflammation and supporting restoration of a stable ocular surface that is able to counteract graft failure, with no toxicity for the transplanted LSC. Keywords: stem cells, bevacizumab, limbal stem cell deficiency, transplantation

  10. Evaluation of febrile neutropenia in patients undergoing hematopoietic stem cell transplantation.

    Directory of Open Access Journals (Sweden)

    Shahideh Amini

    2014-01-01

    Full Text Available The aim of this study was to determine the incidence and causes of fever as a major problem contributing to transplantation related mortality among patients undergoing hematopoietic stem cell transplantation (HSCT and evaluation of antibiotic use, according to reliable guidelines.We retrospectively reviewed hospital records of 195 adult patients who underwent HSCT between 2009-2011 at hematology-oncology and bone marrow transplantation research center. Baseline information and also data related to fever and neutropenia, patient's outcomes, duration of hospitalization and antibiotic use pattern were documented.A total of 195 patients were analyzed and a total of 268 febrile episodes in 180 patients were recorded (mean 1.5 episodes per patient. About 222 episodes (82% were associated with neutropenia which one-fourth of them were without any documented infection sources. Microbiologic documents showed that the relative frequencies of gram positive and gram negative bacteria were 62.5% and 37.5%, respectively. The hospital stay duration was directly related to the numbers of fever episodes (P<0.0001.The rate of febrile episodes in autologous stem cell transplantation was significantly higher compared to allogeneic type (P<0.05.It is necessary to determine not only the local profile of microbiologic pattern, but also antibiotic sensitivities in febrile neutropenic patients following hematopoietic stem cell transplantation, and reassess response to antibiotic treatment to establish any necessity for modifications to treatment guidelines in order to prevent any fatal complications from infection.

  11. How to Improve the Survival of Transplanted Mesenchymal Stem Cell in Ischemic Heart?

    Directory of Open Access Journals (Sweden)

    Liangpeng Li

    2016-01-01

    Full Text Available Mesenchymal stem cell (MSC is an intensely studied stem cell type applied for cardiac repair. For decades, the preclinical researches on animal model and clinical trials have suggested that MSC transplantation exerts therapeutic effect on ischemic heart disease. However, there remain major limitations to be overcome, one of which is the very low survival rate after transplantation in heart tissue. Various strategies have been tried to improve the MSC survival, and many of them showed promising results. In this review, we analyzed the studies in recent years to summarize the methods, effects, and mechanisms of the new strategies to address this question.

  12. Autologous stem cell transplantation as first line treatment after incomplete excision of pancreatoblastoma.

    Science.gov (United States)

    Meneses, Clarice Franco; Osório, Carolina Dame; de Castro Junior, Claudio Galvão; Brunetto, Algemir Lunardi

    2013-01-01

    Pancreatoblastoma is a rare tumor and surgery with complete resection is the main treatment approach. Prognosis for patients with residual disease after surgery is usually dismal. A 14-year-old girl with pancreatoblastoma in the pancreatic body and tail was submitted to preoperative chemotherapy. She underwent surgery and the tumor was resected with microscopic margins. Postoperative chemotherapy was followed by high dose chemotherapy and autologous hematopoietic stem cell transplantation. After four years she remains very well with no evidence of disease. This is the first case reported of pancreatoblastoma that was treated with autologous hematopoietic stem cell transplantation as first line treatment without radiotherapy at the site of the microscopic disease.

  13. Black hairy tongue associated with allo peripheral blood hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    LUO Yi; ZOU Ping; LI Qiu-bai; YOU Yong

    2010-01-01

    @@ Tongue lesions resulting from mucositis are a frequent complication of high-dose chemotherapy and irradiation. They are very common in patients with hematopoietic stem cell transplantation, and tongue lesions due to other causes have also been reported. Black hairy tongue (BHT) is a special tongue lesion, not rare in the population with tobacco abuse, but so far it has not been reported after allo peripheral blood hematopoietic stem cell transplantation (allo-PBHST). Here we presented a patient who developed BHT after allo-PBHST and discussed the factors that may cause this condition.

  14. Hematopoietic Stem-Cell Transplantation in the Developing World: Experience from a Center in Western India

    Directory of Open Access Journals (Sweden)

    Chirag A. Shah

    2015-01-01

    Full Text Available We describe our experience of first 50 consecutive hematopoietic stem-cell transplants (HSCT done between 2007 and 2012 at the Apollo Hospital, Gandhinagar, 35 autologous HSCT and 15 allogeneic HSCT. Indications for autologous transplant were multiple myeloma, non-Hodgkin lymphoma, Hodgkin lymphoma, and acute myeloid leukemia, and indications for allogeneic transplants were thalassemia major, aplastic anaemia, chronic myeloid leukemia, and acute lymphoblastic and myeloid leukaemia. The median age of autologous and allogeneic patient’s cohort was 50 years and 21 years, respectively. Median follow-up period for all patients was 39 months. Major early complications were infections, mucositis, acute graft versus host disease, and venoocclusive disease. All of our allogeneic and autologous transplant patients survived during the first month of transplant. Transplant related mortality (TRM was 20% (N = 3 in our allogeneic and 3% (N = 1 in autologous patients. Causes of these deaths were disease relapse, sepsis, hemorrhagic complications, and GVHD. 46% of our autologous and 47% of our allogeneic patients are in complete remission phase after a median follow-up of 39 months. 34% of our autologous patients and 13% of our allogeneic patients had disease relapse. Overall survival rate in our autologous and allogeneic patients is 65.7% and 57.1%, respectively. Our results are comparable to many national and international published reports.

  15. 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....

  16. N-octanoyl Dopamine Attenuates the Development of Transplant Vasculopathy in Rat Aortic Allografts Via Smooth Muscle Cell Protective Mechanisms

    NARCIS (Netherlands)

    Wedel, Johannes; Hottenrott, Maximilia C.; Bulthuis, Marian; Huitema, Sippie; Yard, Benito A.; Hillebrands, Jan-Luuk

    2016-01-01

    Background Transplant vasculopathy (TV) is a major cause for late graft loss after cardiac transplantation. Endothelial damage and T cell infiltration play a pivotal role in the development of TV. Because N-octanoyl dopamine (NOD) inhibits vascular inflammation and suppresses T cell activation in vi

  17. Feasibility of early tapering of cyclosporine following reduced-intensity stem cell transplantation for advanced hematologic or solid malignancies.

    Science.gov (United States)

    Hori, Akiko; Kami, Masahiro; Ohnishi, Mutsuko; Murashige, Naoko; Kojima, Rie; Takaue, Yoichi

    2005-07-01

    Although some researchers have reported that early tapering of cyclosporine is feasible and beneficial to augment graft-versus-leukemia effects after conventional stem-cell transplantation, there is little information on the feasibility of this strategy following reduced-intensity stem cell transplantation (RIST). We summarized outcomes of 17 patients who underwent early tapering of cyclosporine following RIST from HLA-identical siblings.

  18. The Origin of Neointimal Smooth Muscle Cells in Transplant Arteriosclerosis from Recipient Bone-marrow Cells in Rat Aortic Allograft

    Institute of Scientific and Technical Information of China (English)

    SONG Zifang; LI Wei; ZHENG Qichang; SHANG Dan; SHU Xiaogang; GUAN Siming

    2007-01-01

    In order to investigate the origin of neointimal smooth muscle cells in transplant arteriosclerosis in rat aortic allograft, sex-mismatched bone marrow transplantation was performed from male Wistar rats to female Wistar rats. Four weeks after transplantation, the aortic transplant model was established by means of micro-surgery in rats. The recipients were divided into 4 groups: female Wistar-female Wistar aortic isografts, female SD-female Wistar aortic allografts, male SD-male Wistar aortic allografts, female SD-chimera Wistar aortic allografts. Eight weeks after transplantation, aortic grafts were removed at autopsy and processed for histological evaluation and immunohistochemistry. The results indicated that excessive accumulation of α-SMA-positive smooth muscle cells resulted in significant neointima formation and vascular lumen stricture in rat aortic allografts.Neointima assay revealed that the neointimal area and NIA/MA ratio of transplanted artery were significantly increased in all of aortic allograft groups as compared with those in aortic isograft group (P<0.01). Neointimal smooth muscle cells were harvested from cryostat sections of aortic allograft by microdissection method. The Sry gene-specific PCR was performed, and the result showed that a distinct DNA band of 225 bp emerged in the male-male aortic allograft group and chimera aortic allograft group respectively, but not in the female-female aortic allograft group. It was suggested that recipient bone-marrow cells, as the origin of neointimal smooth muscle cells, contributed to the pathological neointimal hyperplasia of aortic allograft and transplant arteriosclerosis.

  19. Loss of immune homeostasis dictates SHIV rebound after stem-cell transplantation

    Science.gov (United States)

    Peterson, Christopher W.; Benne, Clarisse; Polacino, Patricia; Kaur, Jasbir; McAllister, Cristina E.; Filali-Mouhim, Abdelali; Obenza, Willi; Pecor, Tiffany A.; Huang, Meei-Li; Baldessari, Audrey; Murnane, Robert D.; Woolfrey, Ann E.; Klatt, Nichole R.; DeRosa, Stephen; Sékaly, Rafick P.

    2017-01-01

    The conditioning regimen used as part of the Berlin patient’s hematopoietic cell transplant likely contributed to his eradication of HIV infection. We studied the impact of conditioning in simian-human immunodeficiency virus–infected (SHIV-infected) macaques suppressed by combination antiretroviral therapy (cART). The conditioning regimen resulted in a dramatic, but incomplete depletion of CD4+ and CD8+ T cells and CD20+ B cells, increased T cell activation and exhaustion, and a significant loss of SHIV-specific Abs. The disrupted T cell homeostasis and markers of microbial translocation positively correlated with an increased viral rebound after cART interruption. Quantitative viral outgrowth and Tat/rev–induced limiting dilution assays showed that the size of the latent SHIV reservoir did not correlate with viral rebound. These findings identify perturbations of the immune system as a mechanism for the failure of autologous transplantation to eradicate HIV. Thus, transplantation strategies may be improved by incorporating immune modulators to prevent disrupted homeostasis, and gene therapy to protect transplanted cells. PMID:28239658

  20. Allogeneic fetal stem cell transplantation to child with psychomotor retardation: A case report

    Directory of Open Access Journals (Sweden)

    Dajić Katerina

    2016-01-01

    Full Text Available Introduction. The consequences of autologous and allogeneic stem cell transplantation (stem cells of hematopoiesis, applied in adults and children suffering from leukemia or some other malignant disease, are well-known and sufficiently recognizable in pediatric clinical practice regardless of the indication for the treatment. However, the efficacy of fetal stem cell transplantation is unrecognizable when the indications are psychomotor retardation and epilepsy. Case Outline. With the exception of neurological psychiatric problems, a boy aged 9.5 years was in good general health before transplantation with allogeneic fetal stem cells. The main aim of allogeneic fetal stem cell transplantation was treatment of psychomotor retardation and epilepsy. After 13 months of treatment, he was admitted to hospital in a very serious, life-threatening condition due to sepsis and severe pleuropneumonia. The humoral immunity in the boy was adequate, unlike cellular immunity. The immune imbalance in terms of predominance of T-suppressor lymphocytes contributes to delayed and late development of sepsis and severe pleuropneumonia. The boy still shows the same severity of psychomotor retardation, dyslalia, epilepsy, strabismus and amblyopia. Conclusion. Implementation of fetal stem cell therapy for unconfirmed indications abuses the therapeutic approach, harms patients, misleads parents, and brings financial harm to the healthcare system of any country, including Serbia.

  1. Human umbilical cord blood mononuclear cell transplantation for delayed encephalopathy after carbon monoxide intoxication

    Directory of Open Access Journals (Sweden)

    Gong D

    2013-08-01

    Full Text Available Dianrong Gong,1 Haiyan Yu,1 Weihua Wang,2 Haixin Yang,1 Fabin Han1,21Department of Neurology, 2Centre for Stem Cells and Regenerative Medicine, Liaocheng People's Hospital, The Affiliated Liaocheng Hospital, Taishan Medical University, Shandong, People's Republic of ChinaAbstract: Stem cell transplantation is one of the potential treatments for neurological disorders. Since human umbilical cord stem cells have been shown to provide neuroprotection and promote neural regeneration, we have attempted to transplant the human umbilical cord blood mononuclear cells (hUCB-MNCs to treat patients with delayed encephalopathy after carbon monoxide intoxication (DEACOI. The hUCB-MNCs were isolated from fresh umbilical cord blood and were given to patients subarachnoidally. Physical examinations, mini-mental state examination scores, and computed tomography scans were used to evaluate the improvement of symptoms, signs, and pathological changes of the patient's brain before and after hUCB-MNC transplantation. A total of 12 patients with DEACOI were treated with hUCB-MNCs in this study. We found that most of the patients have shown significant improvements in movement, behavior, and cognitive function, and improved brain images in 1–4 months from the first transplantation of hUCB-MNCs. None of these patients have been observed to have any severe adverse effects. Our study suggests that the hUCB-MNC transplantation may be a safe and effective treatment for DEACOI. Further studies and clinical trials with more cases, using more systematic scoring methods, are needed to evaluate brain structural and functional improvements in patients with DEACOI after hUCB-MNC therapy.Keywords: human umbilical cord blood mononuclear cells, transplantation, delayed encephalopathy after carbon monoxide intoxication, MMSE

  2. Endometrial stem cell transplantation in MPTP- exposed primates: an alternative cell source for treatment of Parkinson's disease.

    Science.gov (United States)

    Wolff, Erin F; Mutlu, Levent; Massasa, Efi E; Elsworth, John D; Eugene Redmond, D; Taylor, Hugh S

    2015-01-01

    Parkinson's disease (PD) is a neurodegenerative disease caused by the loss of dopaminergic neurons in the substantia nigra. Cell-replacement therapies have emerged as a promising strategy to slow down or replace neuronal loss. Compared to other stem cell types, endometrium-derived stem cells (EDSCs) are an attractive source of stem cells for cellular therapies because of their ease of collection and vast differentiation potential. Here we demonstrate that endometrium-derived stem cells may be transplanted into an MPTP exposed monkey model of PD. After injection into the striatum, endometrium-derived stem cells engrafted, exhibited neuron-like morphology, expressed tyrosine hydroxylase (TH) and increased the numbers of TH positive cells on the transplanted side and dopamine metabolite concentrations in vivo. Our results suggest that endometrium-derived stem cells may provide a therapeutic benefit in the primate model of PD and may be used in stem cell based therapies.

  3. Renal transplant immunosuppression impairs natural killer cell function in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Olivier Morteau

    Full Text Available Despite an increasing awareness of the importance of innate immunity, the roles of natural killer (NK cells in transplant rejection and antiviral and cancer immunity during immunosuppression have not been clearly defined.To address this issue we have developed a quantitative assay of NK cell function that can be used on clinical samples and have studied the influence of immunosuppression on NK cell function. NK cell degranulation and intracellular interferon (IFN-γ production were determined by flow cytometry of peripheral blood samples.Overnight ex vivo treatment of peripheral blood cells from healthy controls with ciclosporin or tacrolimus inhibited NK cell degranulation and IFN-γ production in a dose-dependent manner. A similar impairment of function was seen in NK cells from patients treated in vivo with calcineurin inhibitors. In the early post-transplant period, there was a variable reduction of NK cell counts after treatment with alemtuzumab and basiliximab.The functional inhibition of NK cells in early transplant patients coincides with the period of maximum susceptibility to viral infections. The ability to assay NK cell function in clinical samples allows assessment of the impact of immunosuppression on these effector cells. This information may be helpful in guiding the titration of immunosuppression in the clinical setting.

  4. Zhichan decoction induces differentiation of dopaminergic neurons in Parkinson’s disease rats after neural stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    Huifen Shi; Jie Song; Xuming Yang

    2014-01-01

    The goal of this study was to increase the dopamine content and reduce dopaminergic metab-olites in the brain of Parkinson’s disease rats. Using high-performance liquid chromatography, we found that dopamine and dopaminergic metabolite (dihydroxyphenylacetic acid and homo-vanillic acid) content in the midbrain of Parkinson’s disease rats was increased after neural stem cell transplantation + Zhichan decoction, compared with neural stem cell transplantation alone. Our genetic algorithm results show that dihydroxyphenylacetic acid and homovanillic acid levels achieve global optimization. Neural stem cell transplantation + Zhichan decoction increased dihydroxyphenylacetic acid levels up to 10-fold, while transplantation alone resulted in a 3-fold increment. Homovanillic acid levels showed no apparent change. Our experimental findings show that after neural stem cell transplantation in Parkinson’s disease rats, Zhichan decoction can promote differentiation of neural stem cells into dopaminergic neurons.

  5. Quantitative assessment of T-cell repertoire recovery after hematopoietic stem cell transplantation

    Science.gov (United States)

    van Heijst, Jeroen W J; Ceberio, Izaskun; Lipuma, Lauren B; Samilo, Dane W; Wasilewski, Gloria D; Gonzales, Anne Marie R; Nieves, Jimmy L; van den Brink, Marcel R M; Perales, Miguel A; Pamer, Eric G

    2012-01-01

    Delayed T-cell recovery and restricted T-cell receptor (TCR) diversity after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are associated with increased risks of infection and cancer relapse. Technical challenges have limited faithful measurement of TCR diversity following allo-HSCT. Here we combined 5′-RACE PCR with deep sequencing, to quantify TCR diversity in 28 allo-HSCT recipients using a single oligonucleotide pair. Analysis of duplicate blood samples confirmed that the frequency of individual TCRs was accurately determined. After 6 months, cord blood graft recipients approximated the TCR diversity of healthy individuals, whereas recipients of T-cell-depleted peripheral blood stem cell grafts had a 28-fold and 14-fold lower CD4+ and CD8+ T-cell diversity, respectively. After 12 months, these deficiencies had improved for the CD4+, but not the CD8+ T-cell compartment. Overall, this method provides unprecedented views of T-cell repertoire recovery after allo-HSCT and may identify patients at high risk of infection or relapse. PMID:23435170

  6. Transplantation of microencapsulated umbilical-cord-bloodderived hepatic-like cells for treatment of hepatic failure

    Institute of Scientific and Technical Information of China (English)

    Fang-Ting Zhang; Hui-Juan Wan; Ming-Hua Li; Jing Ye; Mei-Jun Yin; Chun-Qiao Huang; Jie Yu

    2011-01-01

    AIM:To investigate intraperitoneal transplantation of microencapsulated hepatic-like cells from human umbilical cord blood for treatment of hepatic failure in rats.METHODS:CD34+ cells in umbilical cord blood cells were isolated by magnetic cell sorting.In the in vitro experiment,sorted CD34+ cells were amplified and induced into hepatic-like cells by culturing with a combination of fibroblast growth factor 4 and hepatocyte growth factor.Cultures without growth factor addition served as controls.mRNA and protein levels for hepatic- like cells were analyzed by reverse transcriptionpolymerase chain reaction,immunohistochemistry and immunofluorescence.In the in vivo experiment,the hepatic-like cells were encapsulated and transplanted into the abdominal cavity of acute hepatic failure (AHF) rats at 48 h after D-galactosamine induction of acute hepatic failure.Transplantation with PBS and unencapsulated hepatic-like cells served as controls.The mortality rate,hepatic pathological changes and serum biochemical indexes were determined.The morphology and structure of microcapsules in the greater omentum were observed.RESULTS:Human albumin,alpha-fetoprotein and GATA-4 mRNA and albumin protein positive cells were found among cultured cells after 16 d.Albumin level in culture medium was significantly increased after culturing with growth factors in comparison with culturing without growth factor addition (P < 0.01).Compared with the unencapsulated group,the mortality rate of the encapsulated hepatic-like cell-transplanted group was significantly lower (P < 0.05).Serum biochemical parameters,alanine aminotransferase,aspartate aminotransferase and total bilirubin in the encapsulated group were significantly improvement compared with the PBS control group (P < 0.01).Pathological staining further supported these findings.At 1-2 wk post-transplantation,free microcapsules with a round clear structure and a smooth surface were observed in peritoneal lavage fluid,surviving cells

  7. System for tracking transplanted limbal epithelial stem cells in the treatment of corneal stem cell deficiency (Conference Presentation)

    Science.gov (United States)

    Boadi, Joseph; Matcher, Stephen; MacNeil, Sheila; Sangwan, Virender S.

    2016-04-01

    The prevailing hypothesis for the existence and healing of the avascular corneal epithelium is that this layer of cells are continually produced by stem cells in the limbus and transported onto the cornea to mature into corneal epithelium. In the event that the cornea is damaged and the limbal stem cell population is severely reduced, this condition known as Limbal Stem Cell Deficiency and can lead to blindness. There are numerous treatments but most have high long term failure rates. Most treatment methods include the transplantation of limbal stem cells into damaged limbus with hope of repopulating the region and regenerating at healthy corneal epithelium. Optical Coherence Tomography (OCT) is well known for its high resolution in vivo images. A bespoke OCT has been built to investigate the trajectories of these limbal stem cells after transplantation to see whether if they do repopulate the damaged limbus or not. In the experimentation magneto-labelling was used to track the limbal stem cells. For the magneto-labelling a mixture of limbal stem cells and cornea epithelium are cultured with super paramagnetic iron (Fe3O4) nanoparticles (20-30nm in size) for 24hours, to allow for uptake. The cells are then transplanted onto the denuded cornea. The transplanted cell mixture with the encapsulated magnetic nanoparticles is actuated with an external magnetic field 0.08T leading to a phase modulation on the signal. A Phase sensitive Magneto-motive OCT is used to locate the transplanted cells. The location of the cells with embed SPIOs were located both in 2D and 3D.

  8. Reconstruction of the adenosine system by bone marrow-derived mesenchymal stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    Huicong Kang; Qi Hu; Xiaoyan Liu; Yinhe Liu; Feng Xu; Xiang Li; Suiqiang Zhu

    2012-01-01

    In the present study, we transplanted bone marrow-derived mesenchymal stem cells into the CA3 area of the hippocampus of chronic epilepsy rats kindled by lithium chloride-pilocarpine. Immunofluorescence and western blotting revealed an increase in adenosine A1 receptor expression and a decrease in adenosine A2a receptor expression in the brain tissues of epileptic rats 3 months after transplantation. Moreover, the imbalance in the A1 adenosine receptor/A2a adenosine receptor ratio was improved. Electroencephalograms showed that frequency and amplitude of spikes in the hippocampus and frontal lobe were reduced. These results suggested that mesenchymal stem cell transplantation can reconstruct the normal function of the adenosine system in the brain and greatly improve epileptiform discharges.

  9. Disseminated toxoplasmosis after allogeneic stem cell transplantation in a seronegative recipient.

    Science.gov (United States)

    Osthoff, M; Chew, E; Bajel, A; Kelsey, G; Panek-Hudson, Y; Mason, K; Szer, J; Ritchie, D; Slavin, M

    2013-02-01

    Toxoplasmosis is increasingly diagnosed after hematopoietic stem cell transplantation (HSCT) and is associated with considerable morbidity and mortality. In the majority of cases, reactivation of latent disease secondary to impaired cellular and humoral immunity after HSCT is believed to be the main pathogenetic mechanism. Hence, primary toxoplasmosis is rarely considered in the differential diagnosis of infections after HSCT in a recipient who is seronegative for Toxoplasma gondii pre-transplant. We herein report a seronegative patient with acute T-cell lymphoblastic leukemia, who developed primary disseminated toxoplasmosis 5 months after HSCT from a seronegative unrelated donor. A review of all reported cases of primary toxoplasmosis after HSCT revealed significantly increased morbidity and mortality. Patients with negative pre-transplant Toxoplasma serology should therefore be considered at risk for toxoplasmosis after allogeneic HSCT. Possible prevention and monitoring strategies for seronegative recipients are reviewed and discussed in detail.

  10. Derivation of Traceable and Transplantable Photoreceptors from Mouse Embryonic Stem Cells

    Directory of Open Access Journals (Sweden)

    Sarah Decembrini

    2014-06-01

    Full Text Available Retinal degenerative diseases resulting in the loss of photoreceptors are one of the major causes of blindness. Photoreceptor replacement therapy is a promising treatment because the transplantation of retina-derived photoreceptors can be applied now to different murine retinopathies to restore visual function. To have an unlimited source of photoreceptors, we derived a transgenic embryonic stem cell (ESC line in which the Crx-GFP transgene is expressed in photoreceptors and assessed the capacity of a 3D culture protocol to produce integration-competent photoreceptors. This culture system allows the production of a large number of photoreceptors recapitulating the in vivo development. After transplantation, integrated cells showed the typical morphology of mature rods bearing external segments and ribbon synapses. We conclude that a 3D protocol coupled with ESCs provides a safe and renewable source of photoreceptors displaying a development and transplantation competence comparable to photoreceptors from age-matched retinas.

  11. Reverse seroconversion of hepatitis B virus after hematopoietic stem cell transplantation.

    Science.gov (United States)

    Goyama, S; Kanda, Y; Nannya, Y; Kawazu, M; Takeshita, M; Niino, M; Komeno, Y; Nakamoto, T; Kurokawa, M; Tsujino, S; Ogawa, S; Aoki, K; Chiba, S; Motokura, T; Shiratori, Y; Hirai, H

    2002-11-01

    Hepatitis B virus (HBV) reactivation in patients previously positive for hepatitis B surface antibody (HBsAb), so-called reverse seroconversion, has been considered to be a rare complication after hematopoietic stem cell transplantation (HSCT). We experienced two patients who developed reverse seroconversion among nine who were HBsAb positive and Hepatitis B core antibody (HBcAb) positive before HSCT; one after autologous bone marrow transplantation (BMT) and another after allogeneic peripheral blood stem cell transplantation (PBSCT). We reviewed the literature and considered that reverse seroconversion of HBV after HSCT is not uncommon among HBsAb positive recipients. The use of corticosteroids, the lack of HBsAb in donor, and a decrease in serum HBsAb and HBcAb levels may predict reverse seroconversion after HSCT.

  12. New strategies in hematopoietic stem cell transplantation: G-CSF-mobilized unprocessed whole blood

    Directory of Open Access Journals (Sweden)

    A.M. Dräger

    1998-01-01

    Full Text Available Transplantation of mobilized peripheral blood stem cells (PBSC for rescue of bone marrow function after high-dose chemo-/radiotherapy is widely used in hematologic malignancies and solid tumors. Mobilization of stem cells to the peripheral blood can be achieved by cytokine treatment of the patients. The main advantage of autologous PBSC transplantation over bone marrow transplantation is the faster recovery of neutrophil and platelet counts. The threshold number of PBSC required for adequate rescue of bone marrow is thought to be about 2 x 106 CD34+ cells/kg, if the stem cells are collected by leukapheresis and subsequently cryopreserved. We show that this critical number could be further reduced to as few as 0.2 x 106 cells/kg. In 30 patients with multiple myeloma and 25 patients with bad risk lymphoma 1 liter of granulocyte colony-stimulating factor (G-CSF-mobilized unprocessed whole blood (stored at 4oC for 1-3 days was used for transplantation. Compared to a historical control group, a significant reduction in the duration of neutropenia, thrombocytopenia and the length of hospital stay was documented. Furthermore, the effect of stem cell support was reflected by a lower need for platelet and red cell transfusions and a reduced antibiotic use. Considering the data as a whole, a cost saving of about 50% was achieved. To date, this easy to perform method of transplantation is only feasible following high-dose therapies that are completed within 72 h, since longer storage of unprocessed blood is accompanied by a substantial loss of progenitor cell function. Ongoing investigations include attempts to prolong storage times for whole blood

  13. Optimal Route for Mesenchymal Stem Cells Transplantation after Severe Intraventricular Hemorrhage in Newborn Rats.

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    So Yoon Ahn

    Full Text Available Recently, we showed that intracerebroventricular (IC transplantation of human umbilical cord blood (UCB-derived mesenchymal stem cells (MSCs significantly attenuates posthemorrhagic hydrocephalus (PHH and brain damage after severe IVH in newborn rats. This study was performed to determine the optimal route for transplanting MSCs for severe IVH by comparing IC transplantation, intravenous (IV transplantation, and IV transplantation plus mannitol infusion. Severe IVH was induced by injecting 100 uL of blood into each ventricle of Sprague-Dawley rats on postnatal day 4 (P4. After confirming severe IVH with brain magnetic resonance imaging (MRI at P5, human UCB-derived MSCs were transplanted at P6 by an IC route (1×105, an IV route (5×105, or an IV route with mannitol infused. Follow-up brain MRIs and rotarod tests were performed. At P32, brain tissue samples were obtained for biochemical and histological analyses. Although more MSCs localized to the brain after IC than after IV delivery, both methods were equally effective in preventing PHH; attenuating impaired rotarod test; increasing the number of TUNEL-positive cells, inflammatory cytokines, and astrogliosis; and reducing corpus callosal thickness and myelin basic protein expression after severe IVH regardless of mannitol co-infusion. Despite the superior delivery efficacy with IC than with the IV route, both IC and IV transplantation of MSCs had equal therapeutic efficacy in protecting against severe IVH. These findings suggest that the less invasive IV route might be a good alternative for clinically unstable, very preterm infants that cannot tolerate a more invasive IC delivery of MSCs.

  14. Differentiations of transplanted mouse spermatogonial stem cells in the adult mouse renal parenchyma in vivo

    Institute of Scientific and Technical Information of China (English)

    Da-peng WU; Da-lin HE; Xiang LI; Zhao-hui LIU

    2008-01-01

    Aim:Spermatogonial stem cells can initiate the process of cellular differentia-tion to generate mature spermatozoa, but whether it possess the characteristic of pluripotency and plasticity, similar to embryonic stem cells, has not been elucidated. This study was designed to evaluate the differentiation potential of spermatogonial stem cells into renal cells in vivo. Methods: Neonatal mouse spermatogonial stem cells were transplanted into mature male mice lacking en-dogenous spermatogenesis. The restoration of fertility in recipient males was observed. Spermatogonial stem cells were then injected into renal parenchyma of mature female mice to make a new extracellular environment for differentia-tion. Fluorescence in situ hybridization technology (FISH) was used to detect the expression of chromosome Y in recipient renal tissues. To determine the type of cells differentiated from spermatogonial stem cells, the expression of ricinus communis agglutinin, vimentin, CD45, and F4/80 proteins were examined in the renal tissues by immunohistochemistry. Results: The proliferation of seminiferous epithelial cells was distinctly observed in seminiferous tubules of transplanted testes, whereas no regeneration of spermatogenesis was observed in non-transplanted control testes. In transplanted female renal tissues, FISH showed a much stronger immuno-fluorescence signal of chromosome Y in the nucleolus of epithelial cells of the renal tubule and podocytes of the glomerulus. Conclusion: The spermatogonial stem cells were successfully purified from mouse testicles. This finding demonstrated that spermatogonial stem cells could not only restore damaged spermatogenesis, but were also capable of differentiat-ing into mature renal parenchyma cells in vivo.

  15. Influence of the extracellular matrix on endogenous and transplanted stem cells after brain damage

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    Lars eRoll

    2014-08-01

    Full Text Available The limited regeneration capacity of the adult central nervous system requires strategies to improve recovery of patients. In this context, the interaction of endogenous as well as transplanted stem cells with their environment is crucial. An understanding of the molecular mechanisms could help to improve regeneration by targeted manipulation.In the course of reactive gliosis, astrocytes upregulate Glial fibrillary acidic protein (GFAP and start, in many cases, to proliferate. Beside GFAP, subpopulations of these astroglial cells coexpress neural progenitor markers like Nestin. Although cells express these markers, the proportion of cells that eventually give rise to neurons is limited in many cases in vivo compared to the situation in vitro. In the first section, we present the characteristics of endogenous progenitor-like cells and discuss the differences in their neurogenic potential in vitro and in vivo.As the environment plays an important role for survival, proliferation, migration, and other processes, the second section of the review describes changes in the extracellular matrix (ECM, a complex network that contains numerous signaling molecules. It appears that signals in the damaged central nervous system lead to an activation and de-differentiation of astrocytes, but do not effectively promote neuronal differentiation of these cells. Factors that influence stem cells during development are upregulated in the damaged brain as part of an environment resembling a stem cell niche. We give a general description of the ECM composition, with focus on stem cell-associated factors like the glycoprotein Tenascin-C.Stem cell transplantation is considered as potential treatment strategy. Interaction of transplanted stem cells with the host environment is critical for the outcome of stem cell-based therapies. Possible mechanisms involving the ECM by which transplanted stem cells might improve recovery are discussed in the last section.

  16. Periodontal regeneration in swine after cell injection and cell sheet transplantation of human dental pulp stem cells following good manufacturing practice

    OpenAIRE

    2016-01-01

    Background Periodontitis, one of the most prevalent infectious diseases in humans, results in the destruction of tooth-supporting tissues. The purpose of the present study is to evaluate the effect of cell injection and cell sheet transplantation on periodontal regeneration in a swine model. Methods In the present study, human dental pulp stem cells (hDPSCs) were transplanted into a swine model for periodontal regeneration. Twelve miniature pigs were used to generate periodontitis with bone d...

  17. Transplantability of human lymphoid cell line, lymphoma, and leukemia in splenectomized and/or irradiated nude mice

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, S.; Shimosato, Y.; Kuroki, M.; Sato, Y.; Nakajima, T.

    1980-07-01

    The effects of splenectomy and/or whole-body irradiation of nude mice before xenotransplantation of lymphoid cell lines, lymphoma, and leukemia were studied. Transplantation after whole-body irradiation resulted in the increased ''take'' rate of three cultured cell lines (two of T-cell-derived acute lymphocytic leukemia and one of B-cell derived acute lymphocytic leukemia) and in the tumorous growth of Burkitt-derived Raji and spontaneously transformed lymphoblastoid cell lines. With splenectomy plus irradiation as a pretreatment, tumorous growth occurred in four other cell lines which were not transplantable after irradiation only (two cell lines of Epstein-Barr virus-transformed cord blood cells and one each of null acute lymphocytic leukemia and nodular lymphoma-derived cell lines). Direct transplantation of leukemia and lymphoma cells into the pretreated mice was successful in 7 of 24 cases (29%). B-cell-derived diffuse large lymphoid lymphoma was transplantable in three of seven cases (43%). However, lymphoma and leukemia of peripheral T-cell origin was difficult to transplant even with pretreatment, and only one pleomorphic T-cell lymphoma grew to a significant size (2 cm). One tumor each of B-cell-derived diffuse large lymphoid and T-cell diffuse lymphoblastic lymphoma became transplantable.

  18. Intravenous transplantation of bone marrow-derived mononuclear cells prevents memory impairment in transgenic mouse models of Alzheimer's disease.

    Science.gov (United States)

    Kanamaru, Takuya; Kamimura, Naomi; Yokota, Takashi; Nishimaki, Kiyomi; Iuchi, Katsuya; Lee, Hyunjin; Takami, Shinya; Akashiba, Hiroki; Shitaka, Yoshitsugu; Ueda, Masayuki; Katsura, Ken-Ichiro; Kimura, Kazumi; Ohta, Shigeo

    2015-04-24

    Stem cell transplantation therapy is currently in clinical trials for the treatment of ischemic stroke, and several beneficial aspects have been reported. Similarly, in Alzheimer's disease (AD), stem cell therapy is expected to provide an efficient therapeutic approach. Indeed, the intracerebral transplantation of stem cells reduced amyloid-β (Aβ) deposition and rescued memory deficits in AD model mice. Here, we show that intravenous transplantation of bone marrow-derived mononuclear cells (BMMCs) improves cognitive function in two different AD mouse models, DAL and APP mice, and prevents neurodegeneration. GFP-positive BMMCs were isolated from tibiae and femurs of 4-week-old mice and then transplanted intravenously into DAL and APP mice. Transplantation of BMMCs suppressed neuronal loss and restored memory impairment of DAL mice to almost the same level as in wild-type mice. Transplantation of BMMCs to APP mice reduced Aβ deposition in the brain. APP mice treated with BMMCs performed significantly better on behavioral tests than vehicle-injected mice. Moreover, the effects were observed even with transplantation after the onset of cognitive impairment in DAL mice. Together, our results indicate that intravenous transplantation of BMMCs has preventive effects against the cognitive decline in AD model mice and suggest a potential therapeutic effect of BMMC transplantation therapy.

  19. Treating non-motor symptoms of Parkinson's disease with transplantation of stem cells.

    Science.gov (United States)

    Pantcheva, Paolina; Reyes, Stephanny; Hoover, Jaclyn; Kaelber, Sussannah; Borlongan, Cesar V

    2015-10-01

    Parkinson's disease (PD) treatment-based research has focused on developing therapies for the management of motor symptoms. Non-motor symptoms do not respond to treatments targeting motor deficits, thus necessitating an urgent need to develop new modalities that cater to both motor and non-motor deficits. Stem cell transplantation is potentially therapeutic for PD, but the disease non-motor symptoms have been primarily neglected in such cell therapy regimens. Many types of stem cells are currently available for transplantation therapy, including adult tissue (e.g., bone marrow, placenta)-derived mesenchymal stem cells. The fact that mesenchymal stem cells can replace and rescue degenerated dopaminergic and non-dopaminergic cells suggests their potential for the treatment of motor as well as non-motor symptoms of PD, which is discussed in this article.

  20. Neuromuscular electrical stimulation as a method to maximize the beneficial effects of muscle stem cells transplanted into dystrophic skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Giovanna Distefano

    Full Text Available Cellular therapy is a potential approach to improve the regenerative capacity of damaged or diseased skeletal muscle. However, its clinical use has often been limited by impaired donor cell survival, proliferation and differentiation following transplantation. Additionally, functional improvements after transplantation are all-too-often negligible. Because the host microenvironment plays an important role in the fate of transplanted cells, methods to modulate the microenvironment and guide donor cell behavior are warranted. The purpose of this study was to investigate whether the use of neuromuscular electrical stimulation (NMES for 1 or 4 weeks following muscle-derived stem cell (MDSC transplantation into dystrophic skeletal muscle can modulate the fate of donor cells and enhance their contribution to muscle regeneration and functional improvements. Animals submitted to 4 weeks of NMES after transplantation demonstrated a 2-fold increase in the number of dystrophin+ myofibers as compared to control transplanted muscles. These findings were concomitant with an increased vascularity in the MDSC+NMES group when compared to non-stimulated counterparts. Additionally, animals subjected to NMES (with or without MDSC transplantation presented an increased maximal specific tetanic force when compared to controls. Although cell transplantation and/or the use of NMES resulted in no changes in fatigue resistance, the combination of both MDSC transplantation and NMES resulted in a faster recovery from fatigue, when compared to non-injected and non-stimulated counterparts. We conclude that NMES is a viable method to improve MDSC engraftment, enhance dystrophic muscle strength, and, in combination with MDSC transplantation, improve recovery from fatigue. These findings suggest that NMES may be a clinically-relevant adjunct approach for cell transplantation into skeletal muscle.

  1. Neuroprotective effects of ginsenoside Rg1-induced neural stem cell transplantation on hypoxic-ischemic encephalopathy

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    Ying-bo Li

    2015-01-01

    Full Text Available Ginsenoside Rg1 is the major pharmacologically active component of ginseng, and is reported to have various therapeutic actions. To determine whether it induces the differentiation of neural stem cells, and whether neural stem cell transplantation after induction has therapeutic effects on hypoxic-ischemic encephalopathy, we cultured neural stem cells in 10-80 µM ginsenoside Rg1. Immunohistochemistry revealed that of the concentrations tested, 20 mM ginsenoside Rg1 had the greatest differentiation-inducing effect and was the concentration used for subsequent experiments. Whole-cell patch clamp showed that neural stem cells induced by 20 µM ginsenoside Rg1 were more mature than non-induced cells. We then established neonatal rat models of hypoxic-ischemic encephalopathy using the suture method, and ginsenoside Rg1-induced neural stem cells were transplanted via intracerebroventricular injection. These tests confirmed that neural stem cells induced by ginsenoside had fewer pathological lesions and had a significantly better behavioral capacity than model rats that received saline. Transplanted neural stem cells expressed neuron-specific enolase, and were mainly distributed in the hippocampus and cerebral cortex. The present data suggest that ginsenoside Rg1-induced neural stem cells can promote the partial recovery of complicated brain functions in models of hypoxic-ischemic encephalopathy.

  2. Analysis of CD8+CD28- T-suppressor cells in living donor liver transplant recipients

    Institute of Scientific and Technical Information of China (English)

    Yi-Xin Lin; Lan-Lan Wang; Lu-Nan Yan; Pei Cai; Bo Li; Tian-Fu Wen; Yong Zeng

    2009-01-01

    BACKGROUND: Human CD8+CD28- T-suppressor (Ts) cells have been considered to indicate a reduced need for immunosuppression in pediatric liver-intestine transplant recipients and recipients of deceased heart-kidney transplants. However, in adult-to-adult living donor liver transplantation (A-A LDLT) little information is available and the clinical signiifcance is still unknown. METHODS: Flow cytometry was used to detect the population of CD8+CD28- Ts cells present in peripheral blood in A-A LDLT recipients (n=31), patients with end-stage liver disease (n=24) and healthy controls (n=19). Meanwhile, we tested the graft function and trough levels of immunosuppression in recipients. The clinical and follow-up data of 31 transplant recipients were analyzed. RESULTS: Compared with diseased controls (P=0.007) and healthy individuals (P=0.000), a notable expansion of CD8+CD28- Ts cells was found in recipients of A-A LDLT. This was associated with graft function, levels of immunosuppression and rejection episodes. CONCLUSIONS: To monitor the CD8+CD28- Ts cells levels is important to evaluate the immune state of recipients. Meanwhile, it is also important to promote expansion of CD8+CD28- Ts cells in recipients of A-A LDLT, not only to sustain good graft function and decrease the dosage of immunosuppressants, but also to reduce the occurrence of rejection.

  3. Molecular Mechanisms Mediating Retinal Reactive Gliosis Following Bone Marrow Mesenchymal Stem Cell Transplantation.

    Science.gov (United States)

    Tassoni, Alessia; Gutteridge, Alex; Barber, Amanda C; Osborne, Andrew; Martin, Keith R

    2015-10-01

    A variety of diseases lead to degeneration of retinal ganglion cells (RGCs) and their axons within the optic nerve resulting in loss of visual function. Although current therapies may delay RGC loss, they do not restore visual function or completely halt disease progression. Regenerative medicine has recently focused on stem cell therapy for both neuroprotective and regenerative purposes. However, significant problems remain to be addressed, such as the long-term impact of reactive gliosis occurring in the host retina in response to transplanted stem cells. The aim of this work was to investigate retinal glial responses to intravitreally transplanted bone marrow mesenchymal stem cells (BM-MSCs) to help identify factors able to modulate graft-induced reactive gliosis. We found in vivo that intravitreal BM-MSC transplantation is associated with gliosis-mediated retinal folding, upregulation of intermediate filaments, and recruitment of macrophages. These responses were accompanied by significant JAK/STAT3 and MAPK (ERK1/2 and JNK) cascade activation in retinal Muller glia. Lipocalin-2 (Lcn-2) was identified as a potential new indicator of graft-induced reactive gliosis. Pharmacological inhibition of STAT3 in BM-MSC cocultured retinal explants successfully reduced glial fibrillary acidic protein expression in retinal Muller glia and increased BM-MSC retinal engraftment. Inhibition of stem cell-induced reactive gliosis is critical for successful transplantation-based strategies for neuroprotection, replacement, and regeneration of the optic nerve.

  4. Cumulative Doses of T-Cell Depleting Antibody and Cancer Risk after Kidney Transplantation.

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    Jenny H C Chen

    Full Text Available T-cell depleting antibody is associated with an increased risk of cancer after kidney transplantation, but a dose-dependent relationship has not been established. This study aimed to determine the association between cumulative doses of T-cell depleting antibody and the risk of cancer after kidney transplantation. Using data from the Australian and New Zealand Dialysis and Transplant Registry between 1997-2012, we assessed the risk of incident cancer and cumulative doses of T-cell depleting antibody using adjusted Cox regression models. Of the 503 kidney transplant recipients with 2835 person-years of follow-up, 276 (55%, 209 (41% and 18 (4% patients received T-cell depleting antibody for induction, rejection or induction and rejection respectively. The overall cancer incidence rate was 1,118 cancers per 100,000 patient-years, with 975, 1093 and 1377 cancers per 100,000 patient-years among those who had received 1-5 doses, 6-10 doses and >10 doses, respectively. There was no association between cumulative doses of T cell depleting antibody and risk of incident cancer (1-5: referent, 6-10: adjusted hazard ratio (HR 1.19, 95%CI 0.48-2.95, >10: HR 1.42, 95%CI 0.50-4.02, p = 0.801. This lack of association is contradictory to our hypothesis and is likely attributed to the low event rates resulting in insufficient power to detect significant differences.

  5. Spermatogonial stem cell transplantation into rhesus testes regenerates spermatogenesis producing functional sperm.

    Science.gov (United States)

    Hermann, Brian P; Sukhwani, Meena; Winkler, Felicity; Pascarella, Julia N; Peters, Karen A; Sheng, Yi; Valli, Hanna; Rodriguez, Mario; Ezzelarab, Mohamed; Dargo, Gina; Peterson, Kim; Masterson, Keith; Ramsey, Cathy; Ward, Thea; Lienesch, Maura; Volk, Angie; Cooper, David K; Thomson, Angus W; Kiss, Joseph E; Penedo, Maria Cecilia T; Schatten, Gerald P; Mitalipov, Shoukhrat; Orwig, Kyle E

    2012-11-02

    Spermatogonial stem cells (SSCs) maintain spermatogenesis throughout a man's life and may have application for treating some cases of male infertility, including those caused by chemotherapy before puberty. We performed autologous and allogeneic SSC transplantations into the testes of 18 adult and 5 prepubertal recipient macaques that were rendered infertile with alkylating chemotherapy. After autologous transplant, the donor genotype from lentivirus-marked SSCs was evident in the ejaculated sperm of 9/12 adult and 3/5 prepubertal recipients after they reached maturity. Allogeneic transplant led to donor-recipient chimerism in sperm from 2/6 adult recipients. Ejaculated sperm from one recipient transplanted with allogeneic donor SSCs were injected into 85 rhesus oocytes via intracytoplasmic sperm injection. Eighty-one oocytes were fertilized, producing embryos ranging from four-cell to blastocyst with donor paternal origin confirmed in 7/81 embryos. This demonstration of functional donor spermatogenesis following SSC transplantation in primates is an important milestone for informed clinical translation.

  6. Islet Transplantation

    Science.gov (United States)

    ... transplanted islet cells failed. But in recent years, scientists have begun to make rapid advances in transplant technology, and some of the most exciting new research comes to us from researchers at the University of ... Canada. These scientists have used a new procedure called the Edmonton ...

  7. Bone marrow stromal cell transplantation mitigates radiation-induced gastrointestinal syndrome in mice.

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    Subhrajit Saha

    Full Text Available BACKGROUND: Nuclear accidents and terrorism presents a serious threat for mass casualty. While bone-marrow transplantation might mitigate hematopoietic syndrome, currently there are no approved medical countermeasures to alleviate radiation-induced gastrointestinal syndrome (RIGS, resulting from direct cytocidal effects on intestinal stem cells (ISC and crypt stromal cells. We examined whether bone marrow-derived adherent stromal cell transplantation (BMSCT could restitute irradiated intestinal stem cells niche and mitigate radiation-induced gastrointestinal syndrome. METHODOLOGY/PRINCIPAL FINDINGS: Autologous bone marrow was cultured in mesenchymal basal medium and adherent cells were harvested for transplantation to C57Bl6 mice, 24 and 72 hours after lethal whole body irradiation (10.4 Gy or abdominal irradiation (16-20 Gy in a single fraction. Mesenchymal, endothelial and myeloid population were characterized by flow cytometry. Intestinal crypt regeneration and absorptive function was assessed by histopathology and xylose absorption assay, respectively. In contrast to 100% mortality in irradiated controls, BMSCT mitigated RIGS and rescued mice from radiation lethality after 18 Gy of abdominal irradiation or 10.4 Gy whole body irradiation with 100% survival (p<0.0007 and p<0.0009 respectively beyond 25 days. Transplantation of enriched myeloid and non-myeloid fractions failed to improve survival. BMASCT induced ISC regeneration, restitution of the ISC niche and xylose absorption. Serum levels of intestinal radioprotective factors, such as, R-Spondin1, KGF, PDGF and FGF2, and anti-inflammatory cytokines were elevated, while inflammatory cytokines were down regulated. CONCLUSION/SIGNIFICANCE: Mitigation of lethal intestinal injury, following high doses of irradiation, can be achieved by intravenous transplantation of marrow-derived stromal cells, including mesenchymal, endothelial and macrophage cell population. BMASCT increases blood levels of

  8. Ex vivo expansions and transplantations of mouse bone marrow-derived hematopoietic stem/progenitor cells

    Institute of Scientific and Technical Information of China (English)

    WANG Jin-fu(王金福); WU Yi-fan(吴亦凡); HARRINTONG Jenny; McNIECE Ian K.

    2004-01-01

    To examine the effects of co-culture with bone marrow mesenchymal stem cells on expansion of hematopoietic stem/progenitor cells and the capacities of rapid neutrophil engraftment and hematopoietic reconstitution of the expanded cells, we expanded mononuclear cells (MNCs) and CD34+/c-kit+ cells from mouse bone marrow and transplanted the expanded cells into the irradiated mice. MNCs were isolated from mouse bone marrow and CD34+/c-kit+ cells were selected from MNCs by using MoFlo Cell Sorter. MNCs and CD34+/c-kit+ cells were co-cultured with mouse bone marrow-derived mesenchymal stem cells (MSCs) under a two-step expansion. The expanded cells were then transplanted into sublethally irradiated BDF1 mice. Results showed that the co-culture with MSCs resulted in expansions of median total nucleated cells,CD34+ cells, GM-CFC and HPP-CFC respectively by 10.8-, 4.8-, 65.9- and 38.8-fold for the mononuclear cell culture, and respectively by 76.1-, 2.9-, 71.7- and 51.8-fold for the CD34+/c-kit+ cell culture. The expanded cells could rapidly engraft in the sublethally irradiated mice and reconstitute their hematopoiesis. Co-cultures with MSCs in conjunction with two-step expansion increased expansions of total nucleated cells, GM-CFC and HPP-CFC, which led us to conclude MSCs may create favorable environment for expansions of hematopoietic stem/progenitor cells. The availability of increased numbers of expanded cells by the co-culture with MSCs may result in more rapid engraftment ofneutrophils following infusion to transplant recipients.

  9. Animal experiments and clinical application of olfactory ensheathing cell transplantation for treatment of spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    Nan Liu; Wei Liu; Baiyu Zhou; Jing Wang; Bing Li

    2008-01-01

    BACKGROUND: The olfactory epithelium can still generate new neurons after arresting its growth and development in the human body. Axons can still be generated and pass through peripheral tissue to reach the olfactory bulb. Thus, olfactory cells have been widely used in the repair of spinal cord injury.OBJECTIVE: Using animal experiments in conjunction with a clinical study of olfactory ensheathing cells, this paper was designed to clarify the function and application prospects of olfactory ensheathing cells, as well as the existing problems with their application. RETRIEVAL STRATEGY: Using the terms "olfactory ensheathing cells, spinal cord injury", we retrieved manuscripts published from January 1990 to June 2007. The languages were limited to English and Chinese. Inclusion criteria: studies addressing the characteristics, basic study, clinical application and prospects of olfactory ensheathing cells; studies that were recently published or were published in high-impact journals. Exclusion criteria: repetitive studies.LITERATURE EVALUATION: The included 29 manuscripts were primarily clinical or basic experimental studies. DATA SYNTHESIS: Following spinal cord injury, spinal neurons die, neurotrophic factors are lacking, and the existing glial scar and cavities hinder axonal growth. One method to repair spinal cord injury is to interfere with the above-mentioned factors based on animal experiments. Myelination and axonal regeneration are the keys to spinal cord injury therapy. Olfactory ensheathing cells can secrete several neurotrophic factors, inhibit horizontal cell reactions, have noticeable neuroprotective effects, and possess a very strong reproductive activity, so they have many advantages in the fields of cell transplantation and gene therapy. However, there still exist many questions and uncertainties, such as the best time window and dose, as well as complications of olfactory ensheathing cell transplantation; precise mechanism of action after olfactory

  10. Matched unrelated donor allogeneic transplantation provides comparable long-term outcome to HLA-identical sibling transplantation in relapsed diffuse large B-cell lymphoma

    NARCIS (Netherlands)

    Avivi, I.; Canals, C.; Vernant, J.P.; Wulf, G.; Nagler, A.; Hermine, O.; Petersen, E.; Yakoub-Agha, I.; Craddock, C.; Schattenberg, A.V.; Niederwieser, D.; Thomson, K.; Blaise, D.; Attal, M.; Pfreundschuh, M.; Passweg, J.; Russell, N.; Dreger, P.; Sureda, A.

    2014-01-01

    The objective of this retrospective analysis was to compare outcomes of patients with diffuse large B-cell lymphoma (DLBCL) who received either a matched sibling (sib) or an unrelated donor (URD) allogeneic hematopoietic cell transplantation (allo-HCT). Long-term outcome of 172 DLBCL patients receiv

  11. Therapeutic effect of bortezomib for primary plasma cell leukemia followed by auto/allo stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Ozasa R

    2012-07-01

    Full Text Available Ryotaro Ozasa, Masaaki Hotta, Hideaki Yoshimura, Takahisa Nakanishi, Takeshi Tamaki, Shinya Fujita, Naoto Nakamichi, Michihiko Miyaji, Kazuyoshi Ishii, Tomoki Ito, Shosaku NomuraFirst Department of Internal Medicine, Kansai Medical University, Osaka, JapanAbstract: Plasma cell leukemia (PCL is a rare disease that represents approximately 4% of plasma cell malignant disorders. PCL consists of two variants: primary PCL presents in patients with no previous history of multiple myeloma, while secondary PCL consists of a leukemic transformation in a previously recognized multiple myeloma. Primary PCL is an extremely resistant, rapidly progressive, fatal disease, with a median overall survival of 6.8 months. There is no standard therapeutic strategy, because no treatment option has been prospectively evaluated. We describe a successful case of newly diagnosed primary PCL, treated with a regimen that included bortezomib, followed by auto stem cell transplantation and nonmyeloablative allogeneic stem cell transplantation. Our patient has maintained remission status for over 12 months since undergoing the allogeneic stem cell transplantation. This strategy is promising for PCL, which, though an extremely resistant disease, may become curable.Keywords: plasma cell leukemia, multiple myeloma, bortezomib, stem cell transplantation

  12. Haploidentical Natural Killer Cells Infused before Allogeneic Stem Cell Transplantation for Myeloid Malignancies: A Phase I Trial.

    Science.gov (United States)

    Lee, Dean A; Denman, Cecele J; Rondon, Gabriela; Woodworth, Glenda; Chen, Julianne; Fisher, Tobi; Kaur, Indreshpal; Fernandez-Vina, Marcelo; Cao, Kai; Ciurea, Stefan; Shpall, Elizabeth J; Champlin, Richard E

    2016-07-01

    Allogeneic stem cell transplantation is an effective treatment for high-risk myeloid malignancies, but relapse remains the major post-transplantation cause of treatment failure. Alloreactive natural killer (NK) cells mediate a potent antileukemic effect and may also enhance engraftment and reduce graft-versus-host disease (GVHD). Haploidentical transplantations provide a setting in which NK cell alloreactivity can be manipulated, but they are associated with high rates of GVHD. We performed a phase I study infusing escalating doses of NK cells from an HLA haploidentical-related donor-selected for alloreactivity when possible-as a component of the preparative regimen for allotransplantation from a separate HLA-identical donor. The goal of infusing third-party alloreactive NK cells was to augment the antileukemic effect of the transplantation without worsening GVHD and, thus, improve the overall outcome of hematopoietic transplantation. Twenty-one patients with high-risk acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or chronic myelogenous leukemia refractory or beyond first remission received a preparative regimen with busulfan and fludarabine followed by infusion of apheresis-derived, antibody-selected, and IL-2-activated NK cells. Doses were initially based on total nucleated cell (TNC) content and later based on CD56(+) cells to reduce variability. CD56(+) content ranged from .02 to 8.32 × 10(6)/kg. IL-2, .5 × 10(6) units/m(2) subcutaneously was administered daily for 5 days in the final cohort (n = 10). CD3(+) cells in the NK cell product were required to be transplantation-related causes, and 11 patients died of relapse. Despite the small sample size, survival was highly associated with CD56(+) cells delivered (P = .022) and development of ≥ grade 3 GVHD (P = .006). There were nonsignificant trends toward higher survival rates in those receiving NK cells from KIR ligand-mismatched donors and KIR-B haplotype donors. There was no

  13. Infusion of donor spleen cells and rejection in liver transplant recipients.

    Science.gov (United States)

    Scornik, J C; Lauwers, G Y; Reed, A I; Howard, R J; Dickson, R C; Rosen, C B

    2000-02-01

    Intact or inactivated donor lymphoid cells have been found to downregulate the alloimmune response in a number of experimental models. We conducted a randomized, prospective, double blind, and placebo-controlled trial to determine whether heat-treated donor spleen cells would affect early rejection after liver transplantation. Donor spleen was obtained during organ procurement for 40 patients undergoing liver transplantation. All patients were treated with cyclosporine, azathioprine and steroids. The patients were randomized after surgery to receive either heat-treated (45 degrees C for 1 h) spleen cells or placebo. Patients underwent protocol biopsies at 1 wk, 4 and 12 months, or as needed. Biopsies were reviewed in a blind fashion and scored according to the Banff consensus criteria. Randomization resulted in 19 patients in the spleen cell group and 21 in the placebo group. One-yr graft survival was 94 and 100%, respectively. Early rejection was more frequent in the spleen cell group (61 vs. 35%, p, not significant). The histopathological rejection activity index at 7 d was also higher for the patients in the spleen cell group: 39% of spleen cell treated patients had a score of 4 or higher as opposed to 5% in the placebo group (p spleen cell group versus 1.3 + 1.7 for the placebo group (p = 0.034). It is concluded that heat-treated donor spleen cells given within 24 h after liver transplantation were not clinically beneficial and increased the intensity of rejection in 7-d protocol liver biopsies.

  14. Blood Stem Cell Transplant in Treating Patients With Hematologic Cancer

    Science.gov (United States)

    2014-06-05

    Adult Langerhans Cell Histiocytosis; Childhood Langerhans Cell Histiocytosis; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms

  15. 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.

  16. Allogeneic haematopoietic stem cell transplantation as a promising treatment for natural killer-cell neoplasms.

    Science.gov (United States)

    Murashige, Naoko; Kami, Masahiro; Kishi, Yukiko; Kim, Sung-Won; Takeuchi, Masami; Matsue, Kosei; Kanda, Yoshinobu; Hirokawa, Makoto; Kawabata, Yoshinari; Matsumura, Tomoko; Kusumi, Eiji; Hirabayashi, Noriyuki; Nagafuji, Koji; Suzuki, Ritsuro; Takeuchi, Kengo; Oshimi, Kazuo

    2005-08-01

    The efficacy of allogeneic haematopoietic stem-cell transplantation (allo-HSCT) for natural killer (NK)-cell neoplasms is unknown. We investigated the results of allo-HSCT for NK-cell neoplasms between 1990 and 2003 through questionnaires. After reclassification by a haematopathologist, of 345 patients who underwent allo-HSCT for malignant lymphoma, 28 had NK-cell neoplasms (World Health Organization classification): extranodal NK/T-cell lymphoma (n=22), blastic NK-cell lymphoma (n=3), and aggressive NK-cell leukaemia (n=3). Twelve were chemosensitive and 16 chemorefractory. Twenty-two had matched-related donors. Stem-cell source was bone marrow in eight and mobilised peripheral blood in 20. Conditioning regimens were myeloablative (n=23) and non-myeloablative (n=5). Grade 2-4 acute graft-versus-host disease (GVHD) and chronic GVHD developed in 12 and 8 respectively. Eight died of disease progression, three of infection, two of acute GVHD, one of veno-occlusive disease, one of interstitial pneumonitis, and one of thrombotic microangiopathy. Two-year progression-free and overall survivals were 34% and 40% respectively (median follow-up, 34 months). All patients who did not relapse/progress within 10 months achieved progression-free survival (PFS) during the follow-up. In multivariate analysis, stem cell source (BM versus peripheral blood; relative risk 3.03), age (>or=40 years vs. <40 years; relative risk 2.85), and diagnoses (extranodal NK/T-cell lymphoma versus others; relative risk 3.94) significantly affected PFS. Allo-HSCT is a promising treatment for NK-cell neoplasms.

  17. Recent Advances in Application of Male Germ Cell Transplantation in Farm Animals

    Directory of Open Access Journals (Sweden)

    Ali Honaramooz

    2011-01-01

    Full Text Available Transplantation of isolated germ cells from a fertile donor male into the seminiferous tubules of infertile recipients can result in donor-derived sperm production. Therefore, this system represents a major development in the study of spermatogenesis and a unique functional assay to determine the developmental potential and relative abundance of spermatogonial stem cells in a given population of testis cells. The application of this method in farm animals has been the subject of an increasing number of studies, mostly because of its potential as an alternative strategy in producing transgenic livestock with higher efficiency and less time and capital requirement than the current methods. This paper highlights the salient recent research on germ cell transplantation in farm animals. The emphasis is placed on the current status of the technique and examination of ways to increase its efficiency through improved preparation of the recipient animals as well as isolation, purification, preservation, and transgenesis of the donor germ cells.

  18. Liver Graft versus Host Disease after Allogeneic Peripheral Stem Cell Transplantation: Update on Etiopathogenesis and Diagnosis.

    Science.gov (United States)

    Mihăilă, R-G

    2016-01-01

    Graft versus host disease (GVHD) is the main complication of allogeneic hematopoietic cell transplantation and is more frequent after peripheral stem cell transplants. Graft versus leukemia or lymphoma component of them is beneficial to eradicate residual tumor mass after previous treatment and conditioning regimen. A severe GVHD may endanger the patient's life. The most important liver manifestations of GVHD are increased serum alkaline phosphatase and bilirubin values. The last allows to estimate the GVHD severity. Sometimes, an increase of aminotransferases can mimic an acute hepatitis. Donor-derived hematopoietic cells appeared to turn in mesenchymal liver cells. Activated CD4(+) T cells, humoral and complement activation, a large number of cytokines and cytokine receptors are involved in GVHD development. Correct and early recognition of GVHD and its differentiation from the other liver diseases are essential for the medical practice.

  19. Optimal time for mesenchymal stem cell transplantation in rats with myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    Chen-yang JIANG; Chun GUI; Ai-na HE; Xin-yang HU; Jie CHEN; Yun JIANG; Jian-an WANG

    2008-01-01

    Background:Bone marrow mesenehymal stem cell(MSC)transplantation is a promising strategy in the treatment of myocardial infarction(MI).However,the time for transplanting cells remains controversial.The aim of this study was to find an optimal time point for cell transplantation.Methods:MSCs were isolated and cultured from Sprague-Dawley(SD) rats.MI model was set up in SD rats by permanent ligation of left anterior descending coronary artery.MSCs were directly injected into the infarct berder zone at 1 h,1 week and 2 weeks after MI,respectively.Sham-operated and MI centrel groups received equal volume of phosphate buffered saline(PBS).At 4 weeks after MI,cardiac function Was assessed by echocardiography;vessel density Was analyzed on hematoxylin-eosin stained slides by light microscopy;the apoptosis of cardiomyocytes Was evaluated by terminal deoxynucleotidy1 transferase-mediated dUTP nick end-labeling(TUNEL) assay;the expressions of proteins were analyzed by Western blot.Results:MSC transplantation improved cardiac function.reduced the apoptosis of cardiomyocytes and increased vessel density.These benefits were more obvious in l-week group than in 1-h and 2-week groups.There are more obvious increases in the ratio of bc1-2/bax and the expression of vascular endothelial growth factor(VEGF)and more obvious decreases in the expression of cleaved-caspase-3 in 1-week group than those in other two groups.Conclusion:MSC transplantation was beneficial for the recovery of cardiac function.MSC transplantation at l week post-MI exerted the best effects on increases of cardiac function,anti-apoptosis and angiogenesis.

  20. Migration and distribution of bone marrow stromal cells in injured spinal cord with different transplantation techniques

    Institute of Scientific and Technical Information of China (English)

    FAN Li; DU Fei; CHENG Bang-chang; PENG Hao; LIU Shi-qing

    2008-01-01

    To study the regularity of migration and distribution of bone marrow stromal cells (BMSCs)in iniured spinal cord with intradural space transplantation.Methods:Forty Wistar rats were randomly assigned into 4 groups. The spinal cord injury,model was prepared according to the modified Allen method. BMSCs were labeled by CM-Dil. And 5.0×10 6 cells were transplanted by different channels including intraventricular injection(Group A),injured spinal cord intrathecally injection(Group B),remote intrathecally injection at the L3-L4 level(Group C),and intravenous injection(Group D). Spinal cord was dissected at 24 hours,1,2,3 and 4 weeks after transplantation.Sections of 4 μm were cut on a cryostat and observed under fluorescence microscopy.Results:No fluorescence was observed 24 hours after transplantation in spinal cord injury parenchyma except Group B. One week later,BMSCs in Groups A and C began to migrate to the injured parenchyma;2-4 weeks later,BMSCs penetrated into the injured parenchyma except Group D.The number of BMSCS decreased at 3-4 weeks after transplantation. The number of cells in Group B decreased faster than that of Groups A and C.Conclusions:BMSCs transplanted through intraventricular injection,injured spinal cord intrathecally injection and remote intrathecal injection could migrate to the injured parenchyma of spinal cord effectively. The number of BMSCs migrated into injured spinal cord parenchyma is rare by intravenous injection.

  1. Expanded autologous adipose derived stem cell transplantation for type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Phuong Thi-Bich Le

    2016-12-01

    Full Text Available Introduction: Type 2 diabetes mellitus (T2D is the most common form of diabetes mellitus, accounting for 90% of diabetes mellitus in patients. At the present time, althoughT2D can be treated by various drugs and therapies using insulin replacement, reports have shown that complications including microvascular, macrovascular complications and therapy resistance can occur in patients on long term treatment. Stem cell therapy is regarded as a promising therapy for diabetes mellitus, including T2D. The aim of this study was to evaluate the safety and therapeutic effect of expanded autologous adipose derived stem cell (ADSC transplantation for T2D treatment; the pilot study included 3 patients who were followed for 3 months. Methods: The ADSCs were isolated from stromal vascular fractions, harvested from the belly of the patient,and expanded for 21 days per previously published studies. Before transplantation, ADSCs were evaluated for endotoxin, mycoplasma contamination, and karyotype.All patients were transfused with ADSCs at 1-2x106 cells/kg of body weight.Patients were evaluated for criteria related to transplantation safety and therapeutic effects; these included fever, blood glucose level before transplantation of ADSCs, and blood glucose level after transplantation (at 1, 2 and 3 months. Results: The results showed that all samples of ADSCs exhibited the MSC phenotype with stable karyotype (2n=46, there was no contamination of mycoplasma, and endotoxin levels were low (<0.25 EU/mL. No adverse effects were detected after 3 months of transplantation. Decreases of blood glucose levels were recorded in all patients. Conclusion: The findings from this initial study show that expanded autologous ADSCs may be a promising treatment for T2D.

  2. Optimization of pediatric haematopoietic stem cell transplant outcomes through the application of pharmacokinetics and supportive care

    NARCIS (Netherlands)

    Dupuis, L.L.E.

    2013-01-01

    The research described in this thesis aims to optimize drug-related outcomes in children undergoing haematopoietic stem cell transplant (HSCT). The use of pharmacokinetics to individualize exposure to busulfan and cyclosporine; the assessment of the symptom burden of children receiving chemotherapy

  3. Interleukin-8 transcripts in mononuclear cells determine impaired graft function after kidney transplantation

    DEFF Research Database (Denmark)

    Borst, Christoffer; Xia, Shengqiang; Bistrup, Claus

    2015-01-01

    OBJECTIVE: Interleukin-8 (IL-8) has been associated with ischemia reperfusion injury after renal allograft transplantation. Impaired allograft function may cause major impact on patient morbidity and health care costs. We investigated whether transcript levels in mononuclear cells including IL-8 ...

  4. Salisphere derived c-Kit(+) cell transplantation restores tissue homeostasis in irradiated salivary gland

    NARCIS (Netherlands)

    Nanduri, Lalitha S. Y.; Lombaert, Isabelle M. A.; van der Zwaag, Marianne; Faber, Hette; Brunsting, Jeanette F.; van Os, Ronald P.; Coppes, Robert P.

    2013-01-01

    Introduction: During radiotherapy salivary glands of head and neck cancer patients are unavoidably co-irradiated, potentially resulting in life-long impairment. Recently we showed that transplantation of salisphere-derived c-Kit expressing cells can functionally regenerate irradiated salivary glands

  5. Infection and Coinfection of Human Rhinovirus C in Stem Cell Transplant Recipients

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    Filippo Canducci

    2013-01-01

    Full Text Available In 54 adult stem cell transplant recipients, the presence and persistence of human rhinoviruses (including the novel lineage C were evaluated by molecular detection and phylogenetic analysis, independently from respiratory symptoms. In the same group of patients, the presence of other coinfecting respiratory pathogens, including the novel enterovirus 109, was also evaluated.

  6. 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...

  7. Human bone marrow mesenchymal stem cell transplantation attenuates axonal injur y in stroke rats

    Institute of Scientific and Technical Information of China (English)

    Yi Xu; Shiwei Du; Xinguang Yu; Xiao Han; Jincai Hou; Hao Guo

    2014-01-01

    Previous studies have shown that transplantation of human bone marrow mesenchymal stem cells promotes neural functional recovery after stroke, but the neurorestorative mechanisms remain largely unknown. We hypothesized that functional recovery of myelinated axons may be one of underlying mechanisms. In this study, an ischemia/reperfusion rat model was established using the middle cerebral artery occlusion method. Rats were used to test the hypothesis that in-travenous transplantation of human bone marrow mesenchymal stem cells through the femoral vein could exert neuroprotective effects against cerebral ischemia via a mechanism associated with the ability to attenuate axonal injury. The results of behavioral tests, infarction volume analysis and immunohistochemistry showed that cerebral ischemia caused severe damage to the myelin sheath and axons. After rats were intravenously transplanted with human bone marrow mesenchymal stem cells, the levels of axon and myelin sheath-related proteins, including mi-crotubule-associated protein 2, myelin basic protein, and growth-associated protein 43, were elevated, infarct volume was decreased and neural function was improved in cerebral ischemic rats. These ifndings suggest that intravenously transplanted human bone marrow mesenchymal stem cells promote neural function. Possible mechanisms underlying these beneifcial effects in-clude resistance to demyelination after cerebral ischemia, prevention of axonal degeneration, and promotion of axonal regeneration.

  8. Mitochondrial Neurogastrointestinal Encephalomyopathy Treated with Stem Cell Transplantation: A Case Report and Review of Literature.

    Science.gov (United States)

    Peedikayil, Musthafa Chalikandy; Kagevi, Eje Ingvar; Abufarhaneh, Ehab; Alsayed, Moeenaldeen Dia; Alzahrani, Hazzaa Abdulla

    2015-06-01

    Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive disorder. The mutation in the ECGF1 gene causes severe deficiency of thymidine phosphorylase (TP), which in turn increases thymidine and deoxyuridine in the blood, serum, and tissue. The toxic levels of these products cause malfunction of the mitochondrial respiratory chain and mitochondrial DNA. Commonly, patients become symptomatic between 15 and 20 years of age (range 5 months to 35 years). The most commonly affected systems are gastrointestinal, followed by ocular, and nervous system. The disease is often fatal; high mortality rate is reported between 20 and 40 years of age. Treatment modalities that can increase thymidine phosphorylase activity and decrease thymidine and deoxy-uridine have shown symptomatic improvements in patients with MNGIE. Platelet transfusion, hemodialysis, peritoneal dialysis or allogeneic hematopoietic stem cell transplantation (HSCT) have been tried. The survival and long-term benefits of these measures are still not clear. Engrafted patients after stem cell transplantation have showed improvements in serum thymidine and deoxyuridine. We are reporting a case of MNGIE from Saudi Arabia, who underwent allogeneic hematopoietic stem cell transplantation. No MNGIE case has been previously reported from Saudi Arabia or the Gulf Arab countries. From the available literature, so far only 11 patients with MNGIE have undergone stem cell transplantation.

  9. The prognostic value of YKL-40 concentrations in nonmyeloablative conditioning allogeneic hematopoietic cell transplantation

    DEFF Research Database (Denmark)</