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Sample records for autologous hematopoietic cell

  1. SECOND MALIGNANCIES AFTER AUTOLOGOUS HEMATOPOIETIC CELL TRANSPLANTATION IN CHILDREN

    OpenAIRE

    Danner-Koptik, Karina E; Majhail, Navneet S.; Brazauskas, Ruta; Wang, Zhiwei; Buchbinder, David; Cahn, Jean-Yves; Dilley, Kimberley J.; Frangoul, Haydar A.; Gross, Thomas G.; Hale, Gregory A.; Hayashi, Robert J.; Hijiya, Nobuko; Kamble, Rammurti T.; Lazarus, Hillard M.; Marks, David I.

    2012-01-01

    Childhood autologous hematopoietic cell transplant (AHCT) survivors can be at risk for secondary malignant neoplasms (SMNs). We assembled a cohort of 1,487 pediatric AHCT recipients to investigate the incidence and risk factors for SMNs. Primary diagnoses included neuroblastoma (39%), lymphoma (26%), sarcoma (18%), CNS tumors (14%), and Wilms tumor (2%). Median follow-up was 8 years (range,

  2. SHIPi Enhances Autologous and Allogeneic Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Sandra Fernandes

    2015-03-01

    Full Text Available Hematopoietic stem cell transplantation (HSCT is a highly effective procedure enabling long-term survival for patients with hematologic malignancy or heritable defects. Although there has been a dramatic increase in the success rate of HSCT over the last two decades, HSCT can result in serious, sometimes untreatable disease due to toxic conditioning regimens and Graft-versus-Host-Disease. Studies utilizing germline knockout mice have discovered several candidate genes that could be targeted pharmacologically to create a more favorable environment for transplant success. SHIP1 deficiency permits improved engraftment of hematopoietic stem-progenitor cells (HS-PCs and produces an immunosuppressive microenvironment ideal for incoming allogeneic grafts. The recent development of small molecule SHIP1 inhibitors has opened a different therapeutic approach by creating transient SHIP1-deficiency. Here we show that SHIP1 inhibition (SHIPi mobilizes functional HS-PC, accelerates hematologic recovery, and enhances donor HS-PC engraftment in both allogeneic and autologous transplant settings. We also observed the expansion of key cell populations known to suppress host-reactive cells formed during engraftment. Therefore, SHIPi represents a non-toxic, new therapeutic that has significant potential to improve the success and safety of therapies that utilize autologous and allogeneic HSCT.

  3. Current state and future directions of autologous hematopoietic stem cell transplantation in systemic lupus erythematosus

    OpenAIRE

    Illei, Gabor G.; Cervera, Ricard; Burt, Richard K.; Doria, Andrea; Hiepe, Falk; Jayne, David; Pavletic, Steven; Martin, Thierry; Marmont, Alberto; Saccardi, Riccardo; Voskuyl, Alexandre E; Farge, Dominique

    2011-01-01

    Autologous hematopoietic stem cell transplantation (AHSCT) has been proposed as a treatment modality which may arrest the autoimmune disease process and lead to sustained treatment-free remissions. Since the first consensus statement in 1997, approximately 200 autologous bone marrow or hematopoietic stem cell transplantations have been reported world-wide for SLE. The current state of AHSCT in SLE was reviewed at a recent meeting of the Autoimmune Working Party of the European Group for Blood...

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

    OpenAIRE

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

    2015-01-01

    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.

  5. 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...

  6. Incidence and predictors of congestive heart failure after autologous hematopoietic cell transplantation

    OpenAIRE

    Armenian, Saro H; Sun, Can-Lan; Shannon, Tabitha; Mills, George; Francisco, Liton; Venkataraman, Kalyanasundaram; Wong, F. Lennie; Forman, Stephen J.; Bhatia, Smita

    2011-01-01

    Advances in autologous hematopoietic cell transplantation (HCT) strategies have resulted in a growing number of long-term survivors. However, these survivors are at increased risk of developing cardiovascular complications due to pre-HCT therapeutic exposures and conditioning and post-HCT comorbidities. We examined the incidence and predictors of congestive heart failure (CHF) in 1244 patients undergoing autologous HCT for a hematologic malignancy between 1988 and 2002. The cumulative inciden...

  7. Serum after autologous transplantation stimulates proliferation and expansion of human hematopoietic progenitor cells.

    Directory of Open Access Journals (Sweden)

    Thomas Walenda

    Full Text Available Regeneration after hematopoietic stem cell transplantation (HSCT depends on enormous activation of the stem cell pool. So far, it is hardly understood how these cells are recruited into proliferation and self-renewal. In this study, we have addressed the question if systemically released factors are involved in activation of hematopoietic stem and progenitor cells (HPC after autologous HSCT. Serum was taken from patients before chemotherapy, during neutropenia and after hematopoietic recovery. Subsequently, it was used as supplement for in vitro culture of CD34(+ cord blood HPC. Serum taken under hematopoietic stress (4 to 11 days after HSCT significantly enhanced proliferation, maintained primitive immunophenotype (CD34(+, CD133(+, CD45(- for more cell divisions and increased colony forming units (CFU as well as the number of cobblestone area-forming cells (CAFC. The stimulatory effect decays to normal levels after hematopoietic recovery (more than 2 weeks after HSCT. Chemokine profiling revealed a decline of several growth-factors during neutropenia, including platelet-derived growth factors PDGF-AA, PDGF-AB and PDGF-BB, whereas expression of monocyte chemotactic protein-1 (MCP-1 increased. These results demonstrate that systemically released factors play an important role for stimulation of hematopoietic regeneration after autologous HSCT. This feedback mechanism opens new perspectives for in vivo stimulation of the stem cell pool.

  8. Fractionated stem cell infusions for patients with plasma cell myeloma undergoing autologous hematopoietic cell transplantation.

    Science.gov (United States)

    Landau, Heather; Wood, Kevin; Chung, David J; Koehne, Guenther; Lendvai, Nikoletta; Hassoun, Hani; Lesokhin, Alexander; Hoover, Elizabeth; Zheng, Junting; Devlin, Sean M; Giralt, Sergio

    2016-08-01

    We conducted a phase II trial investigating the impact of fractionated hematopoietic cell infusions on engraftment kinetics and symptom burden in patients with plasma cell myeloma (PCM) undergoing autologous hematopoietic cell transplant (AHCT). We hypothesized that multiple hematopoietic cell infusions would reduce duration of neutropenia and enhance immune recovery resulting in a better tolerated procedure. Twenty-six patients received high-dose melphalan followed by multiple cell infusions (Days 0, +2, +4, +6) and were compared to PCM patients (N = 77) who received high-dose melphalan and a single infusion (Day 0) (concurrent control group). The primary endpoint was number of days with ANC Inventory. Median duration of neutropenia was similar in study (4 days, range 3-5) and control patients (4 days, range 3-9) (p = 0.654). There was no significant difference in the number of red cell or platelet transfusions, days of fever, diarrhea, antibiotics, number of documented infections, or length of admission. Symptom burden surveys showed that AHCT was well-tolerated in both study and control patients. We conclude that fractionated stem cell infusions following high-dose melphalan do not enhance engraftment kinetics or significantly alter patients' clinical course following AHCT in PCM. PMID:26758672

  9. Stomatitis-Related Pain in Women with Breast Cancer Undergoing Autologous Hematopoietic Stem Cell Transplant

    OpenAIRE

    Fall-Dickson, Jane M.; Mock, Victoria; Berk, Ronald A.; Grimm, Patricia M.; Davidson, Nancy; Gaston-Johansson, Fannie

    2008-01-01

    The purpose of this cross-sectional, correlational study was to describe stomatitis-related pain in women with breast cancer undergoing autologous hematopoietic stem cell transplant. Hypotheses tested were that significant, positive relationships would exist between oral pain and stomatitis, state anxiety, depression, and alteration in swallowing. Stomatitis, sensory dimension of oral pain, and state anxiety were hypothesized to most accurately predict oral pain overall intensity. Thirty-two ...

  10. Renal function in high dose chemotherapy and autologous hematopoietic cell support treatment for breast cancer.

    Science.gov (United States)

    Merouani, A; Shpall, E J; Jones, R B; Archer, P G; Schrier, R W

    1996-09-01

    Autologous and allogeneic bone marrow grafting both require cytoreductive therapy but only the allogeneic procedure requires immunosuppressive agents. Allogeneic bone marrow transplantation has been reported to be associated with a high incidence of both renal failure and veno-occlusive disease (VOD) of the liver, the combination of which is associated with a high morbidity and mortality. There is less known about the frequency and severity of these complications in patients undergoing autologous bone marrow transplantation. In the present study renal, hepatic and other complications were examined in 232 patients with Stages II/III and IV breast cancer who were treated with high-dose chemotherapy and autologous hematopoietic cell support with either marrow or peripheral blood progenitor cells. The post-treatment severity of the renal dysfunction was classified as follows: Grade 0, normal renal function [ 25% decrement in GFR but twofold rise in serum creatinine but no need for dialysis; Grade 3 > than twofold rise in serum creatinine and need for dialysis. There were 102 patients (44%) who were classified as Grade 0 and 81 patients (35%) who were classified as Grade 1 renal dysfunction. Severe renal dysfunction (Grades 2 and 3) was observed in 49 of the 232 patients (21%). This severe renal dysfunction of 21% compares with a previously reported 53% incidence of severe renal dysfunction for allogeneic bone marrow transplantation. Similarly, the frequency of hepatic VOD was less (4.7% or 11 of 232 patients) in this autologous bone marrow transplant study as compared to a reported incidence of hepatic VOD ranging from 22 to 53% in large series of allogeneic bone marrow transplant patients. The severe renal dysfunction (Grades 2 and 3) in the present autologous hematopoietic cell support study correlated most significantly with sepsis, liver and pulmonary dysfunction. The major fall in GFR occurred during chemotherapy but before hematopoietic cell support, thus

  11. Physiological problems in patients undergoing autologous and allogeneic hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Sevgisun Kapucu

    2014-01-01

    Full Text Available Objective: Stem cell transplantation is usually performed in an effort to extend the patient′s life span and to improve their quality of life. This study was conducted to determine the postoperative physiological effects experienced by patients who had undergone autologous and allogeneic stem cell transplantation. Methods: The research is a descriptive study conducted with a sample of 60 patients at Stem Cell Transplantation Units in Ankara. Percentile calculation and chi-square tests were used to evaluate the data. Results: When a comparison was made between patients who had undergone allogeneic Hematopoietic stem cell transplantation (HSCT and those who had undergone autologous HSCT, results indicated that problems occurred more often for the allogeneic HSCT patients. The problems included: Digestion (94.3%, dermatological (76.7%, cardiac and respiratory (66.7%, neurological (66.7%, eye (56.7%, infections (26.7% and Graft Versus Host Disease (5 patients. Furthermore, the problems with pain (50%, numbness and tingling (40%, and speech disorders (3 patients were observed more often in autologous BMT patients. Conclusion: Autologous and allogeneic patients experienced most of physical problems due to they receive high doses of chemotherapy. Therefore, it is recommended that an interdisciplinary support team approach should be usedtohelp reduce and manage the problems that may arise during patient care.

  12. Autologous peripheral hematopoietic stem-cell transplantation in a patient with refractory pemphigus

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The aim of this study is to explore the effectiveness of autologous peripheral hematopoietic stem-cell transplantation in the treatment of refractory pemphigus.A 35-year-old male patient presented with a 4-year history of recurrent bullae on his trunk and extremities.The diagnosis of pemphigus was made on the basis of the clinical,histologic and immunofluorescence findings.The patient had shown resistance to conventional therapy with glucocorticoid and immunosuppressive agents.Two months before admission,he complained of hip joint pain.X-ray and CT scan revealed aseptic necrosis of the femoral head.Stem-cell mobilization was achieved by treatment with cyclophosphamide,granulocyte colony-stimulating factor (G-CSF)and rituximab.Peripheral blood stem cells were collected via leukapheresis and cryopreserved for later use.Immunoablation was accomplished by using cyclophosphamide(200 mg/kg;divided into 50 mg/kg on days-5,-4,-3,and-2),antithymocyte globulin(ATG;10 mg/kg;divided into 2.5 mg/kg on days-6,-5,-4,and-3),and rituximab (1200 mg/d;divided into 600 mg/d on days 0 and 7).Autologous peripheral hematopoietic stem cell transplantation was followed by reconstitution of the immune system which was monitored by flow cytometry.The glucocorticoid was withdrawn immediately after transplantation.The pemphigus titer turned negative 6 weeks after transplantation and remained negative.The patient was in complete drug-free remission with no evidence of residual clinical or serological activity of pemphigus during 1 year of followup.The patient's response suggests that autologous peripheral hematopoietic stem cell transplantation may be a potential "cure" for refractory pemphigus.However,further studies are needed to evaluate the risk-benefit ratio of this approach in patients with pemphigus showing resistance to conventional therapy.

  13. Controversies in autologous and allogeneic hematopoietic cell transplantation in peripheral T/NK-cell lymphomas.

    Science.gov (United States)

    Shustov, Andrei

    2013-03-01

    Peripheral T-cell and NK-cell lymphomas (PT/NKCL) are a heterogeneous group of lymphoid neoplasms with poor outcomes. There is no consensus on the best front line therapy or management of relapsed/refractory disease. The use of autologous and allogeneic hematopoietic cell transplantation (HCT) has been studied in both settings to improve outcomes. Multiple retrospective and several prospective trials were reported. While at first sight the outcomes in the relapsed/refractory setting appear similar in B-cell and T-cell lymphomas when treated with high dose therapy (HDT) and autologous HCT, it is becoming obvious that only specific subtypes of PTCL benefit from this approach (i.e. anaplastic large cell lymphoma [ALCL] and angioimmunoblastic lymphoma [AITL] in second CR). In less favorable histologies, HDT seems to provide limited benefit, with the majority of patients experiencing post-transplant relapse. The use of autologous HCT to consolidate first remission has been evaluated in several prospective trials. Again, the best results were observed in ALCL, but the superiority of this approach over chemotherapy alone needs confirmation in randomized trials. In less favorable histologies, high-dose consolidation resulted in low survival rates comparable to those obtained with chemotherapy alone, and without randomized trials it is hard to recommend this strategy to all patients with newly diagnosed PT/NKCL. Allogeneic HCT might provide potent and potentially curative graft-vs-lymphoma effect and overcome chemotherapy resistance. Only a few studies have been reported to date on allogeneic HCT in PT/NKCL. Based on available data, eligible patients benefit significantly from this approach, with 50% or more patients achieving long-term disease control or cure, although at the expense of significant treatment related mortality (TRM). Reduced-intensity conditioning regimens appear to have lower TRM and might extend this approach to older patients. With the recent approval of

  14. Analysis of the feasibility of early hospital discharge after autologous hematopoietic stem cell transplantation and the implications to nursing care

    OpenAIRE

    Alessandra Barban; Fabio Luiz Coracin; Priscila Tavares Musqueira; Andrea Barban; Lilian Piron Ruiz; Milton Artur Ruiz; Rosaura Saboya; Frederico Luiz Dulley

    2014-01-01

    INTRODUCTION: Autologous hematopoietic stem cell transplantation is a conduct used to treat some hematologic diseases and to consolidate the treatment of others. In the field of nursing, the few published scientific studies on nursing care and early hospital discharge of transplant patients are deficient. Knowledge about the diseases treated using hematopoietic stem cell transplantation, providing guidance to patients and caregivers and patient monitoring are important nursing activities in ...

  15. Immune reconstitution after autologous hematopoietic stem cell transplantation 

    OpenAIRE

    João, Cristina Maria Pires

    2007-01-01

    Abstract The investigation of the web of relationships between the different elements of the immune system has proven instrumental to better understand this complex biological system. This is particularly true in the case of the interactions between B and T lymphocytes, both during cellular development and at the stage of cellular effectors functions. The understanding of the B–T cells interdependency and the possibility to manipulate this relationship may be directly applicable t...

  16. Localized extramedullary relapse after autologous hematopoietic stem cell transplantation in multiple myeloma

    International Nuclear Information System (INIS)

    Extramedullary plasmacytomas are rare manifestation of plasma cell malignancies. After hematopoietic stem cell transplantation HSCT, presentation of localized plasmacytoma with extramedullary growth is very unusual. We report a case of a 56-year-old woman with Dune-Salmon stage IIIA immunoglobulin A-kappa multiple myeloma, which presented 120 days after autologous HSCT with extramedullary plasmacytoma arising from a lymph node in supraclavicular region. The patient had no pretransplant-history related with extramedullary disease. There was no increase of plasma cells in bone marrow or monoclonal protein in urine or serum. Aspiration smears of lymph node revealed a population of plasmacytoid cells at various stages of maturation. The patient was successfully treated with local radiotherapy and has remained progression-free for more than 20 months. (author)

  17. Preimmunization of donor lymphocytes enhances antitumor immunity of autologous hematopoietic stem cell transplantation

    International Nuclear Information System (INIS)

    Lymphopenia-induced homeostatic proliferation (HP) of T cells following autologous hematopoietic stem cell transplantation (HSCT) skews the T-cell repertoire by engaging tumor-associated antigens (TAAs), leading to an induction of antitumor immunity. Here, as the tumor-reactive lymphocytes preferentially proliferate during the condition of HP, we examined whether the priming of a donor lymphocytes to TAAs could enhance HP-induced antitumor immunity in autologous HSCT recipients. First, to examine whether the tumor-bearing condition of donor influences the antitumor effect of HSCT, the lymphocytes isolated from CT26 tumor-bearing mice were infused into lethally irradiated mice. The growth of tumors was substantially suppressed in the mice that received HSCT from a tumor-bearing donor compared with a naïve donor, suggesting that a fraction of donor lymphocytes from tumor-bearing mice are primed in response to TAAs and remain responsive upon transplantation. We previously reported that type I interferon (IFN) maturates the dendritic cells and promotes the priming of T cells. We then investigated whether the further priming of donor cells by IFN-α can strengthen the antitumor effect of HSCT. The intratumoral IFN-α gene transfer significantly increased the number of IFN-γ-positive lymphocytes in response to CT26 cells but not the syngeneic lymphocytes in donor mice. The infusion of primed donor lymphocytes markedly suppressed the tumor growth in recipient mice, and cured 64% of the treated mice. Autologous HSCT with the infusion of primed donor lymphocytes is a promising strategy to induce an effective antitumor immunity for solid cancers

  18. Long-term multilineage engraftment of autologous genome-edited hematopoietic stem cells in nonhuman primates.

    Science.gov (United States)

    Peterson, Christopher W; Wang, Jianbin; Norman, Krystin K; Norgaard, Zachary K; Humbert, Olivier; Tse, Collette K; Yan, Jenny J; Trimble, Richard G; Shivak, David A; Rebar, Edward J; Gregory, Philip D; Holmes, Michael C; Kiem, Hans-Peter

    2016-05-19

    Genome editing in hematopoietic stem and progenitor cells (HSPCs) is a promising novel technology for the treatment of many human diseases. Here, we evaluated whether the disruption of the C-C chemokine receptor 5 (CCR5) locus in pigtailed macaque HSPCs by zinc finger nucleases (ZFNs) was feasible. We show that macaque-specific CCR5 ZFNs efficiently induce CCR5 disruption at levels of up to 64% ex vivo, 40% in vivo early posttransplant, and 3% to 5% in long-term repopulating cells over 6 months following HSPC transplant. These genome-edited HSPCs support multilineage engraftment and generate progeny capable of trafficking to secondary tissues including the gut. Using deep sequencing technology, we show that these ZFNs are highly specific for the CCR5 locus in primary cells. Further, we have adapted our clonal tracking methodology to follow individual CCR5 mutant cells over time in vivo, reinforcing that CCR5 gene-edited HSPCs are capable of long-term engraftment. Together, these data demonstrate that genome-edited HSPCs engraft, and contribute to multilineage repopulation after autologous transplantation in a clinically relevant large animal model, an important step toward the development of stem cell-based genome-editing therapies for HIV and potentially other diseases as well. PMID:26980728

  19. High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation for adult histiocytic disorders with central nervous system involvement

    OpenAIRE

    Gaspar, Nathalie; Van Den Neste, Eric; Boudou, Pascaline; Haroche, Julien; Wechsler, Bertrand; Hoang-Xuan, Khe; Amoura, Zahir; Guillevin, Remy; Savatovski, Julien; Azar, Nabih; Piette, Jean-Charles; Leblond, Veronique

    2006-01-01

    We postulated that high-dose chemotherapy (HDC) followed by peripheral autologous hematopoietic stem cell transplantation might help to control refractory central nervous system (CNS) histiocytic disorders. Six patients with histiocytic CNS involvement were treated in this way. Two patients achieved non-active disease status, although one relapsed at 84 months. Two patients had regressive disease, one of whom progressed at 21 months. One patient had progressive disease at 14 months. One patie...

  20. Steroids prevent engraftment syndrome after autologous hematopoietic stem cell transplantation without increasing the risk of infection.

    Science.gov (United States)

    Mossad, S; Kalaycio, M; Sobecks, R; Pohlman, B; Andresen, S; Avery, R; Rybicki, L; Jarvis, J; Bolwell, B

    2005-02-01

    Engraftment syndrome (ES) following autologous hematopoietic stem cell transplantation (AHSCT) is characterized by fever and rash. In January 2002, we instituted steroid prophylaxis for ES from day +4 to +14. This study was conducted to assess whether this practice increased the risk of infection. In total, 194 consecutive patients were reviewed, 111 did not receive steroid prophylaxis (group A), and 83 did (group B). Initial antimicrobial prophylaxis was the same in both groups. There were no significant differences between groups in age, gender, race, prior radiation therapy, number of prior chemotherapy regimens, disease status at transplant, mobilization regimen, days of leukopheresis, CD34(+) cell dose, and days to platelet and neutrophil engraftment. Group B had significantly fewer patients with non-Hodgkin's lymphoma and multiple myeloma, shorter median duration from diagnosis to transplant, lower risk of ES, and shorter mean length of hospital stay. The incidence of early and late microbiologically confirmed infections was not significantly different between groups. Types of infections and types of organisms identified were similar in both groups. Hospital readmission rates were similar in both groups. Steroid prophylaxis significantly decreases the risk of ES following AHSCT, and is associated with shortened hospitalization, without increasing risk of infection. PMID:15640827

  1. Hodgkin's disease as unusual presentation of post-transplant lymphoproliferative disorder after autologous hematopoietic cell transplantation for malignant glioma

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    Scelsi Mario

    2005-08-01

    Full Text Available Abstract Background Post-transplant lymphoproliferative disorder (PTLD is a complication of solid organ and allogeneic hematopoietic stem cell transplantation (HSCT; following autologous HSCT only rare cases of PTLD have been reported. Here, a case of Hodgkin's disease (HD, as unusual presentation of PTLD after autologous HSCT for malignant glioma is described. Case presentation 60-years old man affected by cerebral anaplastic astrocytoma underwent subtotal neurosurgical excision and subsequent high-dose chemotherapy followed by autologous HSCT. During the post HSCT course, cranial irradiation and corticosteroids were administered as completion of therapeutic program. At day +105 after HSCT, the patient developed HD, nodular sclerosis type, with polymorphic HD-like skin infiltration. Conclusion The clinical and pathological findings were consistent with the diagnosis of PTLD.

  2. Epstein-Barr Virus–Associated Posttransplantation Lymphoproliferative Disorder after High-Dose Immunosuppressive Therapy and Autologous CD34-Selected Hematopoietic Stem Cell Transplantation for Severe Autoimmune Diseases

    OpenAIRE

    Nash, Richard A.; Dansey, Roger; Storek, Jan; Georges, George E.; Bowen, James D.; Holmberg, Leona A.; Kraft, George H.; Maureen D Mayes; McDonagh, Kevin T; Chen, Chien-Shing; DiPersio, John; LeMaistre, C. Fred; Pavletic, Steven; Sullivan, Keith M.; Sunderhaus, Julie

    2003-01-01

    High-dose immunosuppressive therapy followed by autologous hematopoietic stem cell transplantation (HSCT) is currently being evaluated for the control of severe autoimmune diseases. The addition of antithymocyte globulin (ATG) to high-dose chemoradiotherapy in the high-dose immunosuppressive therapy regimen and CD34 selection of the autologous graft may induce a higher degree of immunosuppression compared with conventional autologous HSCT for malignant diseases. Patients may be at higher risk...

  3. Improving Outcome of Hodgkins Disease with Autologous Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Raut, Shreeniwas; Shah, Sandip; Shah, Kamalesh; Patel, Kinnari; Talati, Shailesh; Parikh, Sonia; Anand, Asha; Panchal, Harsha; Patel, Apurva; Jain, Akhil

    2016-06-01

    We report analysis of all consecutive Hodgkins disease patients undergoing autologous hematopoietic stem cell transplant from September 1999 to December 2014. Out of total 38 patients 26 were males and 12 were females. 32 were adults and 6 were pediatric (<18 years). None were elderly. Median age was 28 years (9-61). All received BEAM protocol as conditioning regimen. Median engraftment time for granulocytes was 12 and 14 days for platelets. Thirty three (86.84 %) patients achieved complete remission out of which 8 (24.24 %) had further relapse. Transplant related mortality occurred in 4 (10 %) patients. Finally 26 (78.78 %) patients were disease free at median follow up of 60 months and median disease free survival (DFS) was 35 months. DFS was 66.66 and 65 %, respectively on 3 and 5 years. While overall survival was 70.83 and 70 % on 3 and 5  years, respectively. PMID:27065579

  4. A population-based cohort study of late mortality in adult autologous hematopoietic stem cell transplant recipients in Australia.

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    Ashton, Lesley J; Le Marsney, Renate E; Dodds, Anthony J; Nivison-Smith, Ian; Wilcox, Leonie; O'Brien, Tracey A; Vajdic, Claire M

    2014-07-01

    We assessed overall and cause-specific mortality and risk factors for late mortality in a nation-wide population-based cohort of 4547 adult cancer patients who survived 2 or more years after receiving an autologous hematopoietic stem cell transplantation (HSCT) in Australia between 1992 and 2005. Deaths after HSCT were identified from the Australasian Bone Marrow Transplant Recipient Registry and through data linkage with the National Death Index. Overall, the survival probability was 56% at 10 years from HSCT, ranging from 34% for patients with multiple myeloma to 90% for patients with testicular cancer. Mortality rates moved closer to rates observed in the age- and sex-matched Australian general population over time but remained significantly increased 11 or more years from HSCT (standardized mortality ratio, 5.9). Although the proportion of deaths from nonrelapse causes increased over time, relapse remained the most frequent cause of death for all diagnoses, 10 or more years after autologous HSCT. Our findings show that prevention of disease recurrence remains 1 of the greatest challenges for autologous HSCT recipients, while the increasing rates of nonrelapse deaths due to the emergence of second cancers, circulatory diseases, and respiratory diseases highlight the long-term health issues faced by adult survivors of autologous HSCT. PMID:24631736

  5. UPDATE ON THE ROLE OF AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION IN MULTIPLE MYELOMA

    Directory of Open Access Journals (Sweden)

    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.

  6. Spontaneous autologous graft-versus-host disease in plasma cell myeloma autograft recipients: flow cytometric analysis of hematopoietic progenitor cell grafts.

    Science.gov (United States)

    Lazarus, Hillard M; Sommers, Scott R; Arfons, Lisa M; Fu, Pingfu; Ataergin, S A; Kaye, N M; Liu, F; Kindwall-Keller, Tamila L; Cooper, Brenda W; Laughlin, Mary J; Creger, Richard J; Barr, Paul M; Gerson, Stanton L; Kaplan, David

    2011-07-01

    Nine plasma cell myeloma patients spontaneously developed histologically proven autologous graft-versus-host disease (GVHD) limited predominantly to the gastrointestinal tract within 1 month of initial autologous hematopoietic cell transplantation (AHCT) using high-dose melphalan conditioning. All recipients responded promptly to systemic and nonabsorbable oral corticosteroid therapy. All patients previously received systemic therapy with thalidomide, lenalidomide, or bortezomib before AHCT. Using enzymatic amplification staining-enhanced flow cytometry, we evaluated expression of selected transcription regulators, pathway molecules, and surface receptors on samples of the infused hematopoietic cell grafts. We demonstrated significantly enhanced expression of GATA-2, CD130, and CXCR4 on CD34(+) hematopoietic progenitor cells of affected patients compared with 42 unaffected AHCT controls. These 3 overexpressed markers have not been previously implicated in autologous GVHD. Although we did not specifically evaluate T cells, we postulate that exposure over time to the various immunomodulating therapies used for induction treatment affected not only the CD34(+) cells but also T cells or relevant T cell subpopulations capable of mediating GVHD. After infusion, the affected hematopoietic progenitor cells then encounter a host that has been further altered by the high-dose melphalan preparative regimen; such a situation leads to the syndrome. These surface markers could be used to develop a model to predict development of this syndrome. Autologous GVHD potentially is a serious complication of AHCT and should be considered in plasma cell myeloma patients with otherwise unexplained gastrointestinal symptoms in the immediate post-AHCT period. Prompt recognition of this condition and protracted treatment with nonabsorbable or systemic corticosteroids or the combination may lead to resolution. PMID:21440080

  7. Autologous Transplantation of Lentivector/Acid Ceramidase–Transduced Hematopoietic Cells in Nonhuman Primates

    OpenAIRE

    Walia, Jagdeep S; Neschadim, Anton; Lopez-Perez, Orlay; Alayoubi, Abdulfatah; Fan, Xin; Carpentier, Stéphane; Madden, Melissa; Lee, Chyan-Jang; Cheung, Fred; Jaffray, David A.; Levade, Thierry; McCart, J Andrea; Jeffrey A Medin

    2011-01-01

    Farber disease is a rare lysosomal storage disorder (LSD) that manifests due to acid ceramidase (AC) deficiencies and ceramide accumulation. We present a preclinical gene therapy study for Farber disease employing a lentiviral vector (LV-huAC/huCD25) in three enzymatically normal nonhuman primates. Autologous, mobilized peripheral blood (PB) cells were transduced and infused into fully myelo-ablated recipients with tracking for at least 1 year. Outcomes were assessed by measuring the AC speci...

  8. Analysis of the feasibility of early hospital discharge after autologous hematopoietic stem cell transplantation and the implications to nursing care

    Directory of Open Access Journals (Sweden)

    Alessandra Barban

    2014-07-01

    Full Text Available INTRODUCTION: Autologous hematopoietic stem cell transplantation is a conduct used to treat some hematologic diseases and to consolidate the treatment of others. In the field of nursing, the few published scientific studies on nursing care and early hospital discharge of transplant patients are deficient. Knowledge about the diseases treated using hematopoietic stem cell transplantation, providing guidance to patients and caregivers and patient monitoring are important nursing activities in this process. Guidance may contribute to long-term goals through patients' short-term needs. AIM: To analyze the results of early hospital discharge on the treatment of patients submitted to autologous transplantation and the influence of nursing care on this conduct. METHODS: A retrospective, quantitative, descriptive and transversal study was conducted. The hospital records of 112 consecutive patients submitted to autologous transplantation in the period from January to December 2009 were revisited. Of these, 12 patients, who remained in hospital for more than ten days after transplantation, were excluded from the study. RESULTS: The medical records of 100 patients with a median age of 48.5 years (19-69 years were analyzed. All patients were mobilized and hematopoietic stem cells were collected by leukapheresis. The most common conditioning regimes were BU12Mel100 and BEAM 400. Toxicity during conditioning was easily managed in the outpatient clinic. Gastrointestinal toxicity, mostly Grades I and II, was seen in 69% of the patients, 62% of patients had diarrhea, 61% of the patients had nausea and vomiting and 58% had Grade I and II mucositis. Ten patients required hospitalization due to the conditioning regimen. Febrile neutropenia was seen in 58% of patients. Two patients died before Day +60 due to infections, one with aplasia. The median times to granulocyte and platelet engraftment were 12 days and 15 days, respectively, with median red blood cell and

  9. UPDATE ON THE ROLE OF AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION IN MULTIPLE MYELOMA

    Directory of Open Access Journals (Sweden)

    Patrizia Tosi

    2012-01-01

    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.

  10. Quantification of Acute Lymphoblastic Leukemia Clonotypes in Leukapheresed Peripheral Blood Progenitor Cells Predicts Relapse Risk after Autologous Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Mannis, Gabriel N; Martin, Thomas G; Damon, Lloyd E; Andreadis, Charalambos; Olin, Rebecca L; Kong, Katherine A; Faham, Malek; Hwang, Jimmy; Ai, Weiyun Z; Gaensler, Karin M L; Sayre, Peter H; Wolf, Jeffrey L; Logan, Aaron C

    2016-06-01

    Since the incorporation of tyrosine kinase inhibitors into the treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), the notion that all patients with "high-risk" ALL uniformly require allogeneic (allo) hematopoietic cell transplantation (HCT) has received increasing scrutiny. Although multiple studies have shown superiority of alloHCT over autologous (auto) hematopoietic cell transplantation for high-risk patients, these findings may be explained, in part, by contamination of the peripheral blood progenitor cell (PBPC) leukapheresis product by residual leukemic cells in patients undergoing autoHCT. We retrospectively evaluated minimal residual disease (MRD) using next-generation sequencing (NGS) in the PBPC leukapheresis product of 32 ALL patients who underwent autoHCT. Twenty-eight patients (88%) had diagnostic samples with quantifiable immunoreceptor rearrangements to follow for MRD. Twelve (38%) patients had Ph+ B-ALL, 12 (38%) had Philadelphia chromosome-negative (Ph-) B-ALL, and 4 (14%) had T cell ALL. With a median follow-up of 41 months (range, 3 to 217), median relapse-free survival (RFS) and overall survival for the entire cohort were 3.2 and 4.2 years, respectively; at 5 years after transplantation, 42% of patients remain alive and relapse free. Using MRD detection at a threshold of ≥ 1 × 10(-6), median RFS for patients with detectable MRD was 6.5 months and was not reached for patients without detectable disease (P = .0005). In multivariate analysis, the only factor significantly associated with relapse was the presence of MRD ≥1 × 10(-6) (odds ratio, 23.8; confidence interval, 1.8 to 312.9; P = .0158). Our findings suggest that NGS for MRD detection can predict long-term RFS in patients undergoing autoHCT for high-risk ALL. PMID:26899561

  11. Less vasoocclusive disease after intravenous ersus oral busulfan for autologous hematopoietic cell transplantation : the Belgian pediatric experience

    OpenAIRE

    Huybrechts, S.; Beguin, Yves; Ferster, A; Laureys, G; UYTTEBROECK, A; Vermeylen, C

    2012-01-01

    Busulfan is commonly used in preparative conditioning regimens prior to hematopoietic stem cell transplantation in children and young adults for malignant and non-malignant disorders. For many years Busulfan was only available in an oral form, resulting in large inter- and intra-patients variability in plasma exposure, associated with higher graft failure rate as well as higher toxicity such as venoocclusive disease. With the development of an intravenous formulation of Busulfan, a more accur...

  12. Prognostic Value of EMT-Circulating Tumor Cells in Metastatic Breast Cancer Patients Undergoing High-Dose Chemotherapy with Autologous Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Michal Mego, Hui Gao, Bang-Ning Lee, Evan N. Cohen, Sanda Tin, Antonio Giordano, Qiong Wu, Ping Liu, Yago Nieto, Richard E. Champlin, Gabriel N. Hortobagyi, Massimo Cristofanilli, Naoto T. Ueno, James M. Reuben

    2012-01-01

    Full Text Available Background: Circulating tumor cells (CTCs are an independent prognostic factor in metastatic breast cancer (MBC patients treated by conventional dose chemotherapy. The aim of this study was to determine the role of CTCs and CTCs undergoing epithelial-mesenchymal transition (EMT in metastatic breast cancer. We used the platform of high-dose chemotherapy (HDCT and autologous hematopoietic stem cell transplantation (AHSCT to study the CTCs and CTCs with EMT.Patients and methods: CTCs were enumerated in 21 MBC patients before apheresis and 1 month after AHSCT. CD34-depleted apheresis products were analyzed for CD326+ epithelial and Aldefluor+ cancer stem cells (CSC by flow cytometry and were depleted of CD45+ cells and assessed for EMT-inducing transcription factors (EMT-TF by quantitative RT-PCR.Results: Patients with ≥ 5 CTCs/7.5 mL of peripheral blood 1 month after AHSCT had shorter progression-free survival (PFS (P=0.02 and overall survival (OS (P=0.02. Patients with apheresis products containing high percentages of CD326+ epithelial cells or overexpressing EMT-TF had shorter PFS. In multivariate analysis, low percentage of CD326+ epithelial cells and response to HDCT with AHSCT were associated with longer PFS, whereas lower CTCs after AHSCT was associated with longer OS. High CTCs, 1 month after AHSCT correlated with shorter PFS and OS in MBC patients undergoing HDCT and AHSCT, while CTCs with EMT and CSCs phenotype in apheresis products are associated with relapse.Conclusion: Our data suggest that CTC and CTCs with EMT are prognostic in MBC patients undergoing HDCT followed by AHSCT.

  13. Phase I study of temozolomide in combination with thiotepa and carboplatin with autologous hematopoietic cell rescue in patients with malignant brain tumors with minimal residual disease.

    Science.gov (United States)

    Egan, G; Cervone, K A; Philips, P C; Belasco, J B; Finlay, J L; Gardner, S L

    2016-04-01

    Recurrence of malignant brain tumors results in a poor prognosis with limited treatment options. High-dose chemotherapy with autologous hematopoietic cell rescue (AHCR) has been used in patients with recurrent malignant brain tumors and has shown improved outcomes compared with standard chemotherapy. Temozolomide is standard therapy for glioblastoma and has also shown activity in patients with medulloblastoma/primitive neuro-ectodermal tumor (PNET), particularly those with recurrent disease. Temozolomide was administered twice daily on days -10 to -6, followed by thiotepa 300 mg/m(2) per day and carboplatin dosed using the Calvert formula or body surface area on days -5 to -3, with AHCR day 0. Twenty-seven patients aged 3-46 years were enrolled. Diagnoses included high-grade glioma (n=12); medulloblastoma/PNET (n=9); central nervous system (CNS) germ cell tumor (n=4); ependymoma (n=1) and spinal cord PNET (n=1). Temozolomide doses ranged from 100 mg/m(2) per day to 400 mg/m(2) per day. There were no toxic deaths. Prolonged survival was noted in several patients including those with recurrent high-grade glioma, medulloblastoma and CNS germ cell tumor. Increased doses of temozolomide are feasible with AHCR. A phase II study using temozolomide, carboplatin and thiotepa with AHCR for children with recurrent malignant brain tumors is being conducted through the Pediatric Blood and Marrow Transplant Consortium. PMID:26726947

  14. Long-term outcomes of patients with intermediate-risk acute myeloid leukemia treated with autologous hematopoietic cell transplant in first complete remission.

    Science.gov (United States)

    Mannis, Gabriel N; Martin, Thomas G; Damon, Lloyd E; Logan, Aaron C; Olin, Rebecca L; Flanders, Michael D; Ai, Weiyun Z; Gaensler, Karin M L; Kaplan, Lawrence D; Sayre, Peter H; Smith, Catherine C; Wolf, Jeffrey L; Andreadis, Charalambos

    2016-07-01

    In 2014, autologous hematopoietic cell transplant (autoHCT) was removed from the National Comprehensive Cancer Network guidelines as a recommended treatment for patients with intermediate-risk AML in first complete remission (CR1). We reviewed the outcomes of all patients with intermediate-risk AML treated with autoHCT in CR1 at our institution. Of 334 patients who underwent autoHCT for AML between 1988 and 2013, 133 patients with intermediate-risk AML in CR1 were identified. Cytogenetics were diploid in 97 (73%). With a median follow-up of 4.1 years (range 0.1-17), median overall survival (OS) is 6.7 years; at 5 years post-transplant, 59% of patients remain alive and 43% remain relapse-free. Forty-eight percent of relapsing patients proceeded to salvage alloHCT. Our findings demonstrate that nearly half of patients with intermediate-risk AML in CR1 achieve sustained remissions, and that salvage alloHCT is feasible in those who relapse. AutoHCT therefore remains a reasonable option for intermediate-risk patients with AML in CR1. PMID:26490487

  15. Reduction in incidence of early fatal complications of high-dose chemotherapy with autologous hematopoietic stem cell transplantation in Hodgkin lymphoma patients

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    N. V. Zhukov

    2013-01-01

    Full Text Available Traditionally, the concern of fatal complication is a major obstacle to transfer patients with unfavorable course of Hodgkin’s lymphoma tonational transplantation centers. Early mortality after high-dose chemotherapy with autologous hematopoietic stem cell transplantation(HSCT in the Russia, Ukraine and Belarus was assessed in this retrospective multicenter study.Patients and methods. The study included 372 patients with unfavorable course of Hodgkin’s lymphoma received HSCT between 01.1990and 06.2013: 35.5 % patients with primary resistance, 30.6 % with early relapse, 33.1 % with late relapse and 0.8 % during consolidation offirst complete remission.Results. During first 100 days after HSCT died 14 (3.8 % patients, during first year – 31 (8.4 % patients. During the study period a significant decrease in the 100-day and 1-year mortality rate was observed (p < 0.0001 for both. Among patients received HSCT in 1990–1995, 1996–2000, 2001–2005 and 2006–2013 the 100-day mortality was 19.4 %, 6.3 %, 1.1 % and 0.6 %, respectively. 1-year mortality for the same intervals was 32.3 %, 14.7 %, 4.5 % and 1.9 %, respectively.Conclusions. Currently HSCT in patients with unfavorable course of Hodgkin's lymphoma in national transplant centers, accompanied by an extremely low risk of fatal toxicity.

  16. Reduction in incidence of early fatal complications of high-dose chemotherapy with autologous hematopoietic stem cell transplantation in Hodgkin lymphoma patients

    Directory of Open Access Journals (Sweden)

    N. V. Zhukov

    2014-07-01

    Full Text Available Traditionally, the concern of fatal complication is a major obstacle to transfer patients with unfavorable course of Hodgkin’s lymphoma tonational transplantation centers. Early mortality after high-dose chemotherapy with autologous hematopoietic stem cell transplantation(HSCT in the Russia, Ukraine and Belarus was assessed in this retrospective multicenter study.Patients and methods. The study included 372 patients with unfavorable course of Hodgkin’s lymphoma received HSCT between 01.1990and 06.2013: 35.5 % patients with primary resistance, 30.6 % with early relapse, 33.1 % with late relapse and 0.8 % during consolidation offirst complete remission.Results. During first 100 days after HSCT died 14 (3.8 % patients, during first year – 31 (8.4 % patients. During the study period a significant decrease in the 100-day and 1-year mortality rate was observed (p < 0.0001 for both. Among patients received HSCT in 1990–1995, 1996–2000, 2001–2005 and 2006–2013 the 100-day mortality was 19.4 %, 6.3 %, 1.1 % and 0.6 %, respectively. 1-year mortality for the same intervals was 32.3 %, 14.7 %, 4.5 % and 1.9 %, respectively.Conclusions. Currently HSCT in patients with unfavorable course of Hodgkin's lymphoma in national transplant centers, accompanied by an extremely low risk of fatal toxicity.

  17. Low Connexin Channel-Dependent Intercellular Communication in Human Adult Hematopoietic Progenitor/Stem Cells: Probing Mechanisms of Autologous Stem Cell Therapy

    OpenAIRE

    Yang, Jian; Darley, Richard L.; Hallett, Maurice; Evans, W. Howard

    2010-01-01

    Human bone marrow is a clinical source of autologous progenitor stem cells showing promise for cardiac repair following ischemic insult. Functional improvements following delivery of adult bone marrow CD34+ cells into heart tissue may require metabolic/electrical communication between participating cells. Since connexin43 (Cx43) channels are implicated in cardiogenesis and provide intercellular connectivity in the heart, the authors analyzed the expression of 20 connexins (Cx) in CD34+ cells ...

  18. A phase 1/2 study of an adjuvanted varicella-zoster virus subunit vaccine in autologous hematopoietic cell transplant recipients.

    Science.gov (United States)

    Stadtmauer, Edward A; Sullivan, Keith M; Marty, Francisco M; Dadwal, Sanjeet S; Papanicolaou, Genovefa A; Shea, Thomas C; Mossad, Sherif B; Andreadis, Charalambos; Young, Jo-Anne H; Buadi, Francis K; El Idrissi, Mohamed; Heineman, Thomas C; Berkowitz, Elchonon M

    2014-11-01

    Recombinant herpes zoster (HZ) vaccines may be an alternative to the live-attenuated HZ vaccine for immunocompromised individuals. This was a phase 1/2, randomized, observer-blind, placebo-controlled study in adults with multiple myeloma, non-Hodgkin lymphoma (B- or T-cell), Hodgkin lymphoma, or acute myeloid leukemia who had undergone autologous hematopoietic stem-cell transplant 50 to 70 days earlier. Subjects (N = 121) were randomized 1:1:1:1 to receive (at months 0, 1, 3) three doses of 50 μg varicella-zoster virus glycoprotein E (gE) adjuvanted with AS01B, 3 doses of gE adjuvanted with AS01E, 1 dose of saline followed by 2 doses of gE/AS01B, or 3 doses of saline. One month after the last dose (6 months after transplant), frequencies of CD4(+) T cells expressing ≥2 activation markers after induction with gE and anti-gE antibody concentrations were higher with all gE/AS01 regimens than with saline. Both responses persisted up to 1 year in subjects vaccinated with gE/AS01. Immune responses were higher in the gE/AS01B 3-dose group than in the gE/AS01B 2-dose group but not higher than in the gE/AS01E 3-dose group. One serious adverse event (pneumonia) was considered vaccine related. Both formulations and both schedules were immunogenic and well tolerated in this population. This study was registered at www.clinicaltrials.gov as #NCT00920218. PMID:25237196

  19. AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR HIGH-RISK ACUTE LYMPHOBLASTIC LEUKEMIA: NON-RANDOMIZED STUDY WITH A MAXIMUM FOLLOW-UP OF MORE THAN 22 YEARS

    Directory of Open Access Journals (Sweden)

    Grzegorz Helbig

    2014-06-01

    Full Text Available Objective. To evaluate the efficacy and toxicity of autologous hematopoietic stem cell transplantation (AHSCT for high-risk acute lymphoblastic leukemia (ALL. Material and methods. Overall, 128 high-risk ALL patients at a median age of 26 years (range 18-56 years at diagnosis received AHSCT between 1991-2008. Induction treatment was anthracycline-based in all patients. Conditioning regimen consisted of CAV (cyclophosphamide, cytarabine, etoposide in 125 patients whereas 3 subjects received cyclophosphamide and TBI (total body irridation. Bone marrow was stored for 72 hours in 4oC and re-infused 24 hours after conditioning completion. Bone marrow was a source of stem cells in 119 patients, peripheral blood in 2 and 7 subjects received both bone marrow and peripheral blood. Results. With a median follow-up after AHSCT of 1.6 years (range 0.1-22.3 years, the probability of leukemia-free survival (LFS for the whole group at 10 years was 27% and 23% at 20 years. Transplant-related mortality at 100 days after AHSCT was 3.2%.. There was a strong tendency for better LFS for MRD-negative patients if compared with patients who had positive or unknown MRD status at AHSCT (32% vs 23% and 25%, respectively; p=0.06. There was no difference in LFS between B- and T-lineage ALL as well as between patients transplanted in first complete remission (CR1 and CR2. LFS at 10 years for patients with detectable BCR-ABL at transplant was 20% and this was comparable with subjects with negative and missing BCR-ABL status (26% and 28%; p=0.97. Conclusions. The results of AHSCT for high-risk ALL remains unsatisfactory with low probability of long-term LFS.

  20. Comparative efficacy of tandem autologous versus autologous followed by allogeneic hematopoietic cell transplantation in patients with newly diagnosed multiple myeloma: a systematic review and meta-analysis of randomized controlled trials

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    Kharfan-Dabaja Mohamed A

    2013-01-01

    Full Text Available Abstract Background Despite advances in understanding of clinical, genetic, and molecular aspects of multiple myeloma (MM and availability of more effective therapies, MM remains incurable. The autologous-allogeneic (auto-allo hematopoietic cell transplantation (HCT strategy is based on combining cytoreduction from high-dose (chemo- or chemoradio-therapy with adoptive immunotherapy. However, conflicting results have been reported when an auto-allo HCT approach is compared to tandem autologous (auto-auto HCT. A previously published meta-analysis has been reported; however, it suffers from serious methodological flaws. Methods A systematic search identified 152 publications, of which five studies (enrolling 1538 patients met inclusion criteria. All studies eligible for inclusion utilized biologic randomization. Results Assessing response rates by achievement of at least a very good partial response did not differ among the treatment arms [risk ratio (RR (95% CI = 0.97 (0.87-1.09, p = 0.66]; but complete remission was higher in the auto-allo HCT arm [RR = 1.65 (1.25-2.19, p = 0.0005]. Event-free survival did not differ between auto-allo HCT group versus auto-auto HCT group using per-protocol analysis [hazard ratio (HR = 0.78 (0.58-1.05, p = 0.11] or using intention-to-treat analysis [HR = 0.83 (0.60-1.15, p = 0.26]. Overall survival (OS did not differ among these treatment arms whether analyzed on per-protocol [HR = 0.88 (0.33-2.35, p = 0.79], or by intention-to-treat [HR = 0.80 (0.48-1.32, p = 0.39] analysis. Non-relapse mortality (NRM was significantly worse with auto-allo HCT [RR (95%CI = 3.55 (2.17-5.80, p  Conclusion Despite higher complete remission rates, there is no improvement in OS with auto-allo HCT; but this approach results in higher NRM in patients with newly diagnosed MM. At present, totality of evidence suggests that an auto-allo HCT approach for patients with newly diagnosed

  1. Immunoselection techniques in hematopoietic stem cell transplantation.

    Science.gov (United States)

    Li Pira, Giuseppina; Biagini, Simone; Cicchetti, Elisabetta; Merli, Pietro; Brescia, Letizia Pomponia; Milano, Giuseppe Maria; Montanari, Mauro

    2016-06-01

    Hematopoietic Stem Cells Transplantation (HSCT) is an effective treatment for hematological and non-hematological diseases. The main challenge in autologous HSCT is purging of malignant cells to prevent relapse. In allogeneic HSCT graft-versus-host disease (GvHD) and opportunistic infections are frequent complications. Two types of graft manipulation have been introduced: the first one in the autologous context aimed at separating malignant cells from hematopoietic stem cells (HSC), and the second one in allogeneic HSCT aimed at reducing the incidence of GvHD and at accelerating immune reconstitution. Here we describe the manipulations used for cell purging in autologous HSCT or for T Cell Depletion (TCD) and T cell selection in allogeneic HSCT. More complex manipulations, requiring a Good Manufacturing Practice (GMP) facility, are briefly mentioned. PMID:27209628

  2. Role of autologous hematopoietic stem cell transplantation according to the NPM1/FLT3-ITD molecular status for cytogenetically normal AML patients: a GOELAMS study.

    Science.gov (United States)

    Guièze, Romain; Cornillet-Lefebvre, Pascale; Lioure, Bruno; Blanchet, Odile; Pigneux, Arnaud; Recher, Christian; Bonmati, Caroline; Fegueux, Nathalie; Bulabois, Claude-Eric; Bouscary, Didier; Vey, Norbert; Delain, Martine; Turlure, Pascal; Himberlin, Chantal; Harousseau, Jean-Luc; Dreyfus, Francois; Béné, Marie C; Ifrah, Norbert; Chevallier, Patrice

    2012-12-01

    The choice of postremission therapy for acute myeloid leukemia (AML) patients is now based on the blasts' cytogenetic and molecular profile. However, the potential benefit of autologous hematopoietic stem cell transplantation (auto-HSCT) according to the NPM1/FLT3-ITD status has been poorly studied in AML patients with a normal karyotype (NK). Therefore, we evaluated the NPM1/FLT3-ITD molecular status in 135 NK-AML patients treated by allogeneic HSCT (allo-HSCT), auto-HSCT, or chemotherapy as consolidation therapy within the GOELAMS LAM-2001 trial. In univariate analyzes, 4-year leukemia-free survival (LFS) and overall survival (OS) were significantly higher for NPM1+/FLT3-ITD- patients compared with patients presenting another molecular profile (61 vs. 43% and 72 vs. 48%, P = 0.02 and P = 0.01, respectively). In the NPM1+/FLT3-ITD- subgroup, there was no benefit for allo-HSCT or auto-HSCT vs. chemotherapy (4-year LFS: 71, 56, and 60%; 4-year OS: 73, 71, and 60%, respectively; P = NS). For patients with other NPM1/FLT3-ITD molecular profiles, allo-HSCT was found to be the best consolidation therapy, whereas auto-HSCT was associated with a better outcome when compared with chemotherapy (allo-HSCT-, auto-HSCT-, and chemotherapy-related 4-year LFS: 68, 44, and 36%, P = 0.004; 4-year OS: 68, 52, and 29%, respectively, P = 0.02). Our study indicates that allo-HSCT and auto-HSCT provide similar outcomes compared with chemotherapy as consolidation for NPM1+/FLT3-ITD- NK-AML patients. For NK-AML patients with an adverse molecular profile, auto-HSCT could represent an alternative therapeutic approach when no human leukocyte antigen-matched allogeneic donor is available. PMID:22911473

  3. Prospective evaluation of pulmonary function in cancer patients treated with total body irradiation, high-dose melphalan, and autologous hematopoietic stem cell transplantation

    International Nuclear Information System (INIS)

    Pulmonary function tests (standard vital capacity, SVC; total lung capacity, TLC; forced expiratory volume in 1 second-forced vital capacity ratio, FEV1/FVC; carbon monoxide transfer factor, DLCO) were prospectively evaluated in patients (median age 25 years, 13-52 years; median follow-up 20 months, 6-51 months) with Hodgkin's disease (15 patients), non-Hodgkin's lymphoma (9 patients), and inflammatory breast cancer (3 patients) treated with sequential high-dose therapy comprising the following phases over approximately 2 months: (a) cyclophosphamide (7 g/m2); (b) vincristine (1.4 mg/m2), methotrexate (8 g/m2), and cisplatinum (120 mg/m2) or etoposide (2 g/m2); (c) total body irradiation (TBI; 12.5 gy, 5 fractions over 48 hours), intravenous melphalan (120-180 mg/m2), and transplantation of autologous peripheral blood and/or bone marrow hematopoietic stem cells. Within 2 months after transplantation, 12 patients also received 25 Gy radiotherapy boost to mediastinum and clavicular regions. In vivo dosimetry evaluations of fractionated TBI treatments showed that mean radiation dose absorbed by lungs was 12.18 Gy (97.4% of TBI dose). Despite such a high radiation dose, we observed only transient and subclinical decrease of SVC, TLC, and DLCO. The decrease of SVC, TLC, and DLCO was more evident and prolonged in patients receiving radiotherapy boost. All parameters progressively recovered to normal values within 2 years after transplantation. In contrast, FEV1/FVC remained within normal limits in all patients, thus demonstrating the absence of obstructive ventilatory changes. In addition, no interstitial pneumonia was observed

  4. Plerixafor for autologous CD34+ cell mobilization

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    Huda Salman

    2011-02-01

    Full Text Available Huda Salman, Hillard M LazarusDivision of Hematology-Oncology, Blood and Marrow Transplant Program, University Hospitals Case Medical Center, Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH, USAAbstract: High-dose chemotherapy and autologous transplantation of hematopoietic cells is a crucial treatment option for hematologic malignancy patients. Current mobilization regimes often do not provide adequate numbers of CD34+ cells. The chemokine receptor CXCR4 and ligand SDF-1 are integrally involved in homing and mobilization of hematopoietic progenitor cells. Disruption of the CXCR4/SDF-1 axis by the CXCR4 antagonist, plerixafor, has been demonstrated in Phase II and Phase III trials to improve mobilization when used in conjunction with granulocyte colony-stimulating factor (G-CSF. This approach is safe with few adverse events and produces significantly greater numbers of CD34+ cells when compared to G-CSF alone. New plerixafor initiatives include use in volunteer donors for allogeneic hematopoietic cell transplant and in other disease targets.Keywords: plerixafor, autologous hematopoietic cell transplant, CD34, lymphoma, myeloma, granulocyte colony-stimulating factor (G-CSF

  5. Parasitic Infections in Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Jarque, Isidro; Salavert, Miguel; Pemán, Javier

    2016-01-01

    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. PMID:27413527

  6. PARASITIC INFECTIONS IN HEMATOPOIETIC STEM CELL TRANSPLANTATION

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    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.

  7. Transplante de células-tronco hematopoéticas no diabete melito do tipo I Autologous hematopoietic stem cell transplantation in type I diabetes mellitus

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    Júlio C. Voltarelli

    2004-03-01

    Full Text Available Transplantes autólogos de células-tronco hematopoéticas (TACTH para doenças auto-imunes (DAÍ graves e refratárias à terapia convencional têm sido realizados desde 1996, principalmente dirigidos a doenças reumáticas e neurológicas, com resultados encorajadores. De modo geral, dois terços dos pacientes alcançam remissão duradoura da doença auto-imune, embora a morbimortalidade relacionada ao transplante ou à recidiva e progressão da DAI ainda constituam problemas significativos. Baseados nesses resultados e no efeito benéfico da imunossupressão moderada na evolução do diabete melito do tipo I (DM-I, iniciamos, em dezembro de 2003, um protocolo clínico de TACTH para esta doença, em cooperação com a Universidade Northwestern de Chicago, da Universidade de Miami e do National Institutes of Health. Pacientes com DM-I abaixo de 35 anos, diagnosticados há menos de seis semanas ou na fase assintomática ("lua-de-mel" da doença têm suas CTH mobilizadas com ciclofosfamida (2 g/m² e G-CSF, coletadas do sangue periférico e criopreservadas. Após o condicionamento com ciclofosfamida (200 mg/kg e globulina antitimocitária de coelho (4,5 mg/kg e a infusão das CTH autólogas, os pacientes são seguidos por cinco anos em relação aos aspectos clínicos, endocrinológicos e imunológicos do diabete. Este estudo clínico poderá representar uma importante contribuição científica do transplante de medula óssea brasileiro à moderna era de terapia celular de doenças inflamatórias e degenerativas.Autologous hematopoietic stem cell transplantation (AHSCT for severe and refractory autoimmune diseases has been performed since 1996 with encouraging results. In general, two thirds of the patients achieve durable remissions, although morbidity and mortality related to transplantation or to relapse and progression of autoimmune diseases are still significant. Based on those results and on beneficial effects of moderate immunosuppression

  8. Autologous hematopoietic stem cell transplantation and conventional insulin therapy in the treatment of children with newly diagnosed type 1 diabetes: long term follow-up

    Institute of Scientific and Technical Information of China (English)

    Gu Yi; Gong Chunxiu; Peng Xiaoxia; Wei Liya; Su Chang; Qin Miao; Wang Xi'ou

    2014-01-01

    Background It has been indicated that autologous hematopoietic stem cell transplantation (AHST) is a promising treatment to adults with type 1 diabetes,however,the application of AHST therapy to children with type 1 diabetes still needs more data.The aim of this study was to assess the clinical effect of immune intervention combined with AHST and conventional insulin therapy in the treatment of children with newly diagnosed type 1 diabetes.Methods This 1:2 matched case-control study was comprised of 42 children who were newly diagnosed with type 1 diabetes in the Department of Endocrinology,Beijing Children's Hospital from 2009-2010.The case group included 14 patients,who were treated with AHST within the first 3 months after being diagnosed with diabetes at request of their parents during 2009-2010.The control group included 28 patients with newly diagnosed type 1 diabetes at the same period of hospitalization.We compared the baseline and follow-up data of them,including ketoacidosis onset,clinical variables (glycosylated hemoglobin (HbA1c),insulin dosage and serum C-peptide).Results The clinical characteristics of the patients was comparable between the case group and the control group.At 6-12 months ((10.7±4.2) months) after AHST treatment,we found 11 patients in the case group did not stop the insulin therapy,three cases stopped insulin treatment for 2,3 and 11 months,respectively.No diabetic ketoacidosis (DKA) occurred after transplantation in all the patients in the case group.HbA1c in the control group was significant lower than that in the case group (P <0.01),while the insulin dosage and serum C-peptide were not significant different between the two groups (P >0.05).In order to eliminate the honeymoon effect,we performed final follow-up at the 3-5 years ((4.2±1.8) years) after AHST treatment,and found that HbA1c in the control group was still lower than that in the case group (P <0.01); however,the insulin dosage and serum C-peptide were not

  9. Sequential myeloablative autologous stem cell transplantation and reduced intensity allogeneic hematopoietic cell transplantation is safe and feasible in children, adolescents and young adults with poor-risk refractory or recurrent Hodgkin and non-Hodgkin lymphoma.

    Science.gov (United States)

    Satwani, P; Jin, Z; Martin, P L; Bhatia, M; Garvin, J H; George, D; Chaudhury, S; Talano, J; Morris, E; Harrison, L; Sosna, J; Peterson, M; Militano, O; Foley, S; Kurtzberg, J; Cairo, M S

    2015-02-01

    The outcome of children, adolescents and young adults (CAYA) with poor-risk recurrent/refractory lymphoma is dismal (⩽30%). To overcome this poor prognosis, we designed an approach to maximize an allogeneic graft vs lymphoma effect in the setting of low disease burden. We conducted a multi-center prospective study of myeloablative conditioning (MAC) and autologous stem cell transplantation (AutoSCT), followed by a reduced intensity conditioning (RIC) and allogeneic hematopoietic cell transplantation (AlloHCT) in CAYA, with poor-risk refractory or recurrent lymphoma. Conditioning for MAC AutoSCT consisted of carmustine/etoposide/cyclophosphamide, RIC consisted of busulfan/fludarabine. Thirty patients, 16 Hodgkin lymphoma (HL) and 14 non-Hodgkin lymphoma (NHL), with a median age of 16 years and median follow-up of 5years, were enrolled. Twenty-three patients completed both MAC AutoSCT and RIC AlloHCT. Allogeneic donor sources included unrelated cord blood (n=9), unrelated donor (n=8) and matched siblings (n=6). The incidence of transplant-related mortality following RIC AlloHCT was only 12%. In patients with HL and NHL, 10 year EFS was 59.8% and 70% (P=0.613), respectively. In summary, this approach is safe, and long-term EFS with this approach is encouraging considering the poor-risk patient characteristics and the use of unrelated donors for RIC AlloHCT in the majority of cases. PMID:24938649

  10. Co-infusion of autologous adipose tissue derived insulin-secreting mesenchymal stem cells and bone marrow derived hematopoietic stem cells: Viable therapy for type III.C. a diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Umang G Thakkar

    2014-12-01

    Full Text Available Transition from acute pancreatitis to insulin-dependent diabetes mellitus (IDDM is a rare manifestation of primary hyperparathyroidism caused by parathyroid adenoma because of impaired glucose tolerance and suppresses insulin secretion. We report the case of a 26-year-old male with pancreatic diabetes caused by parathyroid adenoma induced chronic pancreatitis. He had serum C-peptide 0.12 ng/ml, glutamic acid decarboxylase antibody 5.0 IU/ml, and glycosylated hemoglobin (HbA1C 8.9%, and required 72 IU/day of biphasic-isophane insulin injection for uncontrolled hyperglycemia. We treated him with his own adipose tissue derived insulin-secreting mesenchymal stem-cells (IS-ADMSC along with his bone marrow derived hematopoietic stem cells (BM-HSC. Autologous IS-ADMSC + BM-HSC were infused into subcutaneous tissue, portal and thymic circulation without any conditioning. Over a follow-up of 27 months, the patient is maintaining fasting and postprandial blood sugar levels of 132 and 165 mg/dl, respectively, with HbA1C 6.8% and requiring 36 IU/day of biphasic-isophane insulin. Co-infusion of IS-ADMSC + BM-HSC offers a safe and viable therapy for type III.C.a Diabetes Mellitus.

  11. Co-infusion of autologous adipose tissue derived insulin-secreting mesenchymal stem cells and bone marrow derived hematopoietic stem cells: viable therapy for type III.C. a diabetes mellitus.

    Science.gov (United States)

    Thakkar, Umang G; Vanikar, Aruna V; Trivedi, Hargovind L

    2013-01-01

    Transition from acute pancreatitis to insulin-dependent diabetes mellitus (IDDM) is a rare manifestation of primary hyperparathyroidism caused by parathyroid adenoma because of impaired glucose tolerance and suppresses insulin secretion. We report the case of a 26-year-old male with pancreatic diabetes caused by parathyroid adenoma induced chronic pancreatitis. He had serum C-peptide 0.12 ng/ml, glutamic acid decarboxylase antibody 5.0 IU/ml, and glycosylated hemoglobin (HbA1C) 8.9%, and required 72 IU/day of biphasic-isophane insulin injection for uncontrolled hyperglycemia. We treated him with his own adipose tissue derived insulin-secreting mesenchymal stem-cells (IS-ADMSC) along with his bone marrow derived hematopoietic stem cells (BM-HSC). Autologous IS-ADMSC + BM-HSC were infused into subcutaneous tissue, portal and thymic circulation without any conditioning. Over a follow-up of 27 months, the patient is maintaining fasting and postprandial blood sugar levels of 132 and 165 mg/dl, respectively, with HbA1C 6.8% and requiring 36 IU/day of biphasic-isophane insulin. Co-infusion of IS-ADMSC + BM-HSC offers a safe and viable therapy for type III.C.a Diabetes Mellitus. PMID:24385073

  12. Lymphoscintigraphy and autologous stem cell implantation

    International Nuclear Information System (INIS)

    Lymphoscintigraphy is the criterion standard technique for the diagnosis of lymphedema. Advances of the application of autologous hematopoietic stem cells in ischemic disorders of lower limbs have increased the attention of researchers in this field. Aim: To determine the usefulness of lymphoscintigraphy for the assessment the efficacy of autologous stem cell implantation in patients with chronic lymphedema of the upper and lower limbs. Methods: Sixty-five patients were included. Clinical evaluation and lymphoscintigraphy were performed before and six months after stem cells implantation. The stem cells implantations were carried out by multiple superficial and deep injections in the trajectory of the lymphatic vessels and also in the inguinal region. A volume of 0.75 to 1.00 mL of cell suspension (1.0-2.2 x 109 stem cells) was administered in each injection site. Lymphoscintigraphy: Whole-body scans were acquired at 20 minutes, 1 hour, and 3 hours after administration of 185 to 259 MBq (5–7mCi) of 99mTc-albumin nanocolloids in the interdigital space of both limbs. The anatomy and function of the lymphatic system were evaluated. Results: Functional assessment before implantation of stem cells showed that 69.2% of the patients had severe lymphatic insufficiency. The 61.5% of patients showed clinical improvement, confirmed by the results of the lymphoscintigraphy. The 46.1% of the cases evaluated showed a clear improvement. The study showed that the isotopic lymphography can evaluate the therapeutic response and its intensity. Conclusion: Lymphoscintigraphy is a useful technique for the evaluation and monitoring of autologous stem cell transplantation in patients with chronic lymphedema. (author)

  13. Chiaroscuro hematopoietic stem cell.

    OpenAIRE

    Quesenberry, P.; Habibian, M. (PhD); Dooner, M; Zhong, S.; Reilly, J; Peters, S.; De Becker, P; Grimaldi, C.; Carlson, J; REDDY, P; Nilsson, S.; Stewart, F. M.

    1998-01-01

    These observations suggest several immediate clinical strategies. In gene therapy, approaches could be targeted to obtain cycling of hematopoietic stem cells and gene-carrying retrovirus vector integration followed by engraftment at an appropriate time interval which favors engraftment. The same type of approach can be utilized for stem cell expansion approaches. Alternatively marrow or peripheral stem cell engraftment can be obtained with minimal to no toxicity in allochimeric strategies in ...

  14. Hematopoietic stem cell transplantation

    OpenAIRE

    Eleftheria Hatzimichael; Mark Tuthill

    2010-01-01

    Eleftheria Hatzimichael1, Mark Tuthill21Department of Haematology, Medical School of Ioannina, University of Ioannina, Ioannina, Greece; 2Department of Medical Oncology, Hammersmith Hospital, Imperial College National Health Service Trust, London, UKAbstract: More than 25,000 hematopoietic stem cell transplantations (HSCTs) are performed each year for the treatment of lymphoma, leukemia, immune-deficiency illnesses, congenital metabolic defects, hemoglobinopathies, and myelodysplastic and mye...

  15. Efficacy and safety of autologous bone marrow derived hematopoietic stem cell transplantation in patients with type 2 DM: A 15 months follow-up study

    Directory of Open Access Journals (Sweden)

    Anil Bhansali

    2014-01-01

    Full Text Available Background: there are dearths of studies describing the effect of autologous bone marrow derived stem cell transplantation (ABMSCT through targeted approach in Type 2 Diabetes Mellitus.This study reports the efficacy and safety of super-selective injection of ABMSCT in T2DM. Materials and Methods: Ten patients (8 men and 2 women with T2DM, with duration of disease >5 years and with documented triple drug failure receiving insulin (0.7 U/Kg/day, metformin and pioglitazone underwent super-selective injection of stem cells into superior pancreaticoduodenal artery under fluoroscopic guidance. The primary outcome measure was decrease in insulin requirement by ≥50% (defined as responders, while secondary endpoints were improvement in glucagon stimulated C-peptide levels, changes in weight, HbA1c, lipid profile and quality of life (QOL at the end of 15 months. Results: Six patients (60% were ′responders′ at 15 months of follow-up showing a reduction in mean insulin requirement by 74% as compared to baseline and one patient was off-insulin till the end of the study. Mean HbA1c reduction in ′responders′ was 1.1% (8.1 ± 0.5% to 7.0 ± 0.6%, P = 0.03, accompanied with a significant improvement in glucagon stimulated C-peptide levels (P = 0.03, Homeostasis Model Assessment -β (P = 0.03 and QOL scores. However, ′non-responders′ did not show any significant alterations in these parameters. No serious adverse events were noted. Conclusion: Our observations indicate that ABMSCT is effective in management of T2DM and its efficacy is maintained over a period of 15 months without any adverse events. However, more number of patients and longer duration of follow-up are required to substantiate these observations.

  16. Autologous hematopoietic stem cell transplantation in combination with immunoablative protocol in secondary progressive multiple sclerosis: A 10-year follow-up of the first transplanted patient

    Directory of Open Access Journals (Sweden)

    Obradović Dragana

    2016-01-01

    Full Text Available Introduction. Multiple sclerosis (MS is an immunemediated disease of the central nervous system that affects young individuals and leads to severe disability. High dose immunoablation followed by autologous hemopoietic stem cell transplantation (AHSCT has been considered in the last 15 years as potentialy effective therapeutic approach for agressive MS. The most recent long-time follow-up results suggest that AHSCT is not only effective for highly aggressive MS, but for relapsing-remitting MS as well, providing long-term remission, or maybe even cure. We presented a 10- year follow-up of the first MS patient being treated by immunoablation therapy and AHSCT. Case report. A 27-year-old male experienced the first symptoms - intermitent numbness and paresthesia of arms and legs of what was treated for two years by psychiatrist as anxiety disorder. After he developed severe paraparesis he was admitted to the Neurology Clinic and diagnosed with MS. Our patient developed aggressive MS with frequent relapses, rapid disability progression and transition to secondary progressive form 6 years after MS onset [the Expanded Disability Status Scale (EDSS 7.0 Ambulation Index (AI 7]. AHSCT was performed, cyclophosphamide was used for hemopoietic stem cell mobilization and the BEAM protocol was used as conditionig regimen. No major adverse events followed the AHSCT. Neurological impairment improved, EDSS 6.5, AI 6 and during a 10-year followup remained unchanged. Brain MRI follow-up showed the absence of gadolinium enhancing lesions and a mild progression of brain atrophy. Conclusion. The patient with rapidly evolving, aggressive, noninflammatory MS initialy improved and remained stable, without disability progression for 10 years, after AHSCT. This kind of treatment should be considered in aggressive MS, or in disease modifying treatment nonresponsive MS patients, since appropriately timed AHSCT treatment may not only prevent disability progression but reduce

  17. A phase 1/2 study of an adjuvanted varicella-zoster virus subunit vaccine in autologous hematopoietic cell transplant recipients

    OpenAIRE

    Stadtmauer, Edward A.; Sullivan, Keith M.; Marty, Francisco M.; Dadwal, Sanjeet S; Papanicolaou, Genovefa A.; Shea, Thomas C.; Mossad, Sherif B.; Andreadis, Charalambos; Young, Jo-Anne H.; Buadi, Francis K; El Idrissi, Mohamed; Heineman, Thomas C.; Berkowitz, Elchonon M.

    2014-01-01

    HCT recipients have increased susceptibility to herpes zoster, but live-attenuated vaccines are not appropriate for highly immunocompromised people.An adjuvanted subunit vaccine against herpes zoster elicits strong immune responses with an acceptable safety profile in adult autologous HCT recipients.

  18. Thrombopoietin and hematopoietic stem cells

    OpenAIRE

    de Graaf, Carolyn A.; Metcalf, Donald

    2011-01-01

    Thrombopoietin (TPO) is the cytokine that is chiefly responsible for megakaryocyte production but increasingly attention has turned to its role in maintaining hematopoietic stem cells (HSCs). HSCs are required to initiate the production of all mature hematopoietic cells, but this differentiation needs to be balanced against self-renewal and quiescence to maintain the stem cell pool throughout life. TPO has been shown to support HSC quiescence during adult hematopoiesis, with the loss of TPO s...

  19. Autologous tumor cell lysate-loaded dendritic cells and cytokine-induced killer cells in combination with autologous hematopoietic stem cell transplatation in the treatment of refractory lymphoma%负载自体肿瘤抗原的DC-CIK细胞联合自体造血干细胞移植治疗难治性淋巴瘤的临床研究

    Institute of Scientific and Technical Information of China (English)

    苏毅; 邵文军; 闵敏; 李莉; 陈健; 范方教; 易海; 付利; 刘阳阳; 邓涛; 孙浩平; 孙薏; 钟国成

    2009-01-01

    目的 观察负载自体肿瘤抗原的DE-CIK细胞联合自体造血干细胞移植治疗难治性淋巴瘤的疗效.方法 选取难治性淋巴瘤35例,采用MAC预处理方案,用自体淋巴瘤抗原致敏DC-CIK细胞,于移植预处理后5-10d,将DC-CIK细胞回输给患者.结果 35例难治性淋巴瘤中,29例完全缓解(82.86%),4例部分缓解(14.43%),移植过程中死亡2例(5.71%)(均死于严重混合性感染).所有完全缓解和部分缓解病例均随访3-49个月:4名部分缓解患者分别于移植后3、6、10、13个月后病情进展死亡;完全缓解患者中有3人于移植后11、17、20个月再次复发死亡;现存活26例.结论 负载自体肿瘤抗原的DC-CIK细胞联合自体造血千细胞移植治疗难治性淋巴瘤高于单纯自体外周血造血干细胞的疗效,且无明显毒副作用.%Objective To study the efficacy and side effect of autologons tumor cell lysate-loaded DC-CIK plus autologous hematopoietic stem cell transplantation in the treatment of refractory lymphoma.Methods Thirty-five cases of refractory lymphoma were recruited,lymphoma antigen-pulsed autologous DE-CIK cells were infused 5-10 days after the MAC conditioning regimen.Results Out of the 35 Cases,complete remission Was achieved in 29(82.8%),partial remission in 4(14.4%).Two patients died during transplantation due to severe mixed infections,with a transplant-related mortality rate of 5.7%.All cases of complete remission and partial remission were followed-up for 3-49 months,4 cases with partial remission died 3,6,10,13 months after transplantation.Three cases with complete remission relapsed 11,17,20 months after transplantation.and the other 26 cases survived until now.Conclusion Autologous tumor cell lysate-loaded DE-CIK combined with autologous hematopoietic stem cell transplantation in the treatment of refractory lymphoma is safe and effective.

  20. Autologous hematopoietic stem cell transplantation for peripheral T cell lymphoma%自体造血干细胞移植治疗外周T细胞淋巴瘤

    Institute of Scientific and Technical Information of China (English)

    潘耀柱; 白海; 王存邦; 葸瑞; 张茜; 王晓靖

    2015-01-01

    BACKGROUND:The incidence rate of peripheral T cel lymphoma is high in Asia, and peripheral T cel lymphoma is aggressive with generaly poor prognosis. However, there is no standard treatment strategy. OBJECTIVE:To retrospectively analyze the therapeutic effect of autologous hematopoietic stem cel transplantation on peripheral T cel lymphoma as wel as relevant toxic and side effects. METHODS:A retrospective review was conducted in 35 patients with peripheral T cel lymphoma who underwent autologous hematopoietic stem cel transplantation from March 2003 to April 2014, including 22 cases of extranodal NK/T-cel lymphoma (nasal type), 1 case of angioimmunoblastic T-cel lymphoma, 8 cases of peripheral T cel lymphoma (non-specific), 3 cases of ALK-positive anaplastic large cel lymphoma, and 1 case of ALK-negative anaplastic large cel lymphoma. Al of 35 patients were classified pathologicaly according to WHO pathological type in 2001 and 2008, and received the high-dose chemotherapy with vincristine, cytarabine, etoposide, mitoxantrone, semustine, cyclophosphamide, and total body irradiation. RESULTS AND CONCLUSION: After a median folow-up of 54 (9-120) months, the probabilities of overal survival and disease-free survival after transplantation were 80% (n=28) and 71% (n=25), respectively. Eight cases (23%) relapsed after transplantation, seven of which died. It was safe with mild and moderate transplantation related side-effects on opportunistic infections, oral cavity mucosa and bladder responses and so on, and there were no severe, life-threatening late complications. Autologous hematopoietic stem cel transplantation may be an effective and safe treatment for peripheral T cel lymphoma, and there is a better benefit in peripheral T cel lymphoma patients with first complete remission.%背景:外周T细胞淋巴瘤亚洲地区发病率高,具有侵袭性,预后普遍较差,目前尚无标准治疗策略。目的:评价自体造血干细胞移植治疗外周T细胞

  1. 自体造血干细胞移植治疗恶性淋巴瘤的研究进展%Recent advance in the treatment of malignant lymplhoma by using autologous hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    杨磊; 徐小红

    2011-01-01

    大剂量化疗联合自体造血干细胞移植(HDT-ASCT)是目前治疗复发难治的弥漫大B细胞淋巴瘤的标准方案,但其在滤泡性淋巴瘤、套细胞淋巴瘤及外周T细胞淋巴瘤治疗上的作用及地位存在争议.根据2010年NCCN非霍奇金淋巴瘤治疗指南建议,HDT-ASCT仍是治疗复发滤泡性淋巴瘤、初治套细胞淋巴瘤及外周T细胞淋巴瘤的重要方法,但需大规模的前瞻性临床试验证实其作用及验证不同类型淋巴瘤最佳的诱导、动员及维持治疗方案.对于HDT-ASCT在霍奇金淋巴瘤中的应用有很多问题需要解决,如预处理方案的选择、自体造血干细胞移植前的最佳化疗周期数、放疗在HDT-ASCT中的应用及二重癌发生的风险等.现就ASCT近年来的研究进展作一综述.%High-dose therapy and autologous hematopoietic stem cell transplant (HDT-ASCT) is the standard treatment for relapsed and refractory diffuse large B cell lymphoma and Hodgkin's lymphoma; however, the role for HDT-ASCT in the treatment of follicular lymphoma ( FL), mantle cell lymphoma ( MCL), and peripheral T cell lymphoma (PTCL) is controversial.According to 2009 NCCN non-Hodgkin's lymphoma clinical practice guidelines, HDT-ASCT is an important element of the treatment of relapsed FL,untreated MCL and PTCL.However, large prospective studies are needed to confirm its role and identify the most optimal induction,mobilization and maintenance regimens.For Hodgkin's lymphoma, there are lots of issues need to be solved, such as the option of chemotherapy-conditioning regimens (preprocessing), the optimal number of chemotherapy cycles prior to HSCT, the use of radiation in ASCT and the risk of second malignancies.This review aims to summarize recent advances in ASCT.

  2. FIFTY YEARS OF MELPHALAN USE IN HEMATOPOIETIC STEM CELL TRANSPLANTATION

    OpenAIRE

    Bayraktar, Ulas D.; Bashir, Qaiser; Qazilbash, Muzaffar; Champlin, Richard E.; Ciurea, Stefan O.

    2012-01-01

    Melphalan remains the most widely used agent in preparative regimens for hematopoietic stem-cell transplantation. From its initial discovery more than 50 years ago, it has been gradually incorporated in the conditioning regimens for both autologous and allogeneic transplantation due to its myeloablative properties and broad antitumor effects as a DNA alkylating agent. Melphalan remains the mainstay conditioning for multiple myeloma and lymphomas; and has been used successfully in preparative ...

  3. Clinical Analysis of Allogeneic Hematopoietic Stem Cell Transplantation for Hodgkin's Lymphoma First Autologous Stem Cell transplant Relapse%异基因造血干细胞移植治疗首例自体移植复发霍奇金淋巴瘤的临床分析

    Institute of Scientific and Technical Information of China (English)

    郭智; 陈惠仁; 刘晓东; 楼金星; 何学鹏

    2012-01-01

    目的 探讨霍奇金淋巴瘤自体移植复发后行异基因造血干细胞2次移植的可能性和安全性.方法 对1例10年前行自体造血干细胞移植复发的霍奇金淋巴瘤患者,行异基因造血干细胞移植,供者为患者母亲,采用外周血干细胞移植,预处理方案采用氟达拉滨+马法兰+兔抗人淋巴细胞免疫球蛋白,预防移植物抗宿主病采用环孢素A、霉酚酸酯、甲氨蝶呤,输注单个核细胞数14.03×108/kg,CD34+细胞6.57×106/kg.结果 2次移植后移植物成功植入,形成完全供者来源造血,移植后第20天骨髓初步植活,造血功能恢复后患者出现皮肤植物抗宿主病,FISH嵌合状态供者细胞植入率为100%,随访至今一直长期无病生存.结论 异基因造血干细胞移植,可有效治疗自体移植复发的霍奇金淋巴瘤,是安全有效的挽救治疗措施.%To investigate the possibility and security of Hodgkin s lymphoma with autologous transplantation relapse treated with allogeneic hematopoietic stem cell transplantation for the second time . Methods A case of autologous hema -topoietic stem cell transplant relapse of Hodgkin s lymphoma patients first treated 10 years ago was treated with allogeneic hemato -poietic stem cell transplantation , donor was the patient s mother, using blood stem cell transplantation , conditioning regimen was fu- dalabin Melphalan anti -THmocyte globulin. Prevention of graft -versus-host disease with cyclosporin A , mycophenolate mofetil, methotrexate. Infusion of the mononuclear cell 14.03 ×108 /kg,CD34+ cells 6. 57 × 106 /kg. Results The second post-transplant graft was successfully implanted to form a complete source of donor hematopoietic and immune function after second hematopoietic stem cell transplantation. Patients had skin graft-versus-host disease after hematopoietic recovery ,20 days later the second transplant of bone marrow preliminary engraftment and follow -up has been a long-term disease-free survival

  4. [Tandem transplantation with peripheral autologous hematopoietic blood stem cells in treatment of oncologic and hematologic malignancies. Initial results of the Donauspital, Vienna].

    Science.gov (United States)

    Ruckser, R; Kier, P; Sebesta, C; Kittl, E; Kurz, M; Selleny, S; Höniger, S; Scherz, M; Habertheuer, K H; Zelenka, P

    1995-01-01

    10 patients were subjected to tandem transplantation for breast cancer (n = 3), ovarian cancer (n = 2) and multiple myeloma (n = 5), at the Second Department of Medicine, Donauspital, Vienna. The breast cancer patients were in stages 2 and 3, respectively, at diagnosis and entered complete remission thereafter. 2 of them developed lymph node metastasis and additional local recurrence, the 3rd patient presented with distant metastasis. The 2 patients with ovarian cancer were in stages Figo III and IV, respectively, at the time of diagnosis, and showed minimal residual disease at second-look-operation. 5 patients with multiple myeloma were in stage 3 pretransplant. Peripheral stem cells were obtained after either high-dose cyclophosphamide or FEC induction and application of cytokines. In 4 patients, tandem transplantation has been completed. 1 patient with multiple myeloma, who had received total body irradiation in combination with chemotherapy for the 2nd transplant, succumbed from idiopathic interstitial pneumonia. No severe clinical complications were observed in all other patients. All patients with solid tumors entered complete remission after the 1st transplantation. 3 of them completed tandem transplantation. Of these, 2 remain in continuous complete remission, the 3rd patient relapsed in lymph nodes day 485. In patients who received only 1 course of high dose chemotherapy with stem cell transplantation, relapses occurred on days 29 and 75, respectively. All patients with multiple myeloma entered only partial remission. We conclude that supralethal chemotherapy with peripheral blood stem cell support is a safe procedure that may at least induce prolonged remissions in solid tumors and hematologic malignancies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7762251

  5. Seguimiento del periodo inmediato post-autotrasplante de células progenitoras hematopoyéticas Follow-up of immediate period of post-autologous hematopoietic progenitor cells transplant

    Directory of Open Access Journals (Sweden)

    Benjamín Ospino

    2012-10-01

    Full Text Available Introducción: el objetivo de este estudio fue describir el comportamiento clínico y de laboratorio presentado en autotrasplante de células progenitoras hematopoyéticas en un grupo de pacientes del Hospital Militar Central en el periodo de enero 2007 a octubre de 2010. Material y métodos: es un estudio descriptivo retrospectivo a través de la revisión de las historias clínicas de estos pacientes obteniendo la información sobre tiempo de alta pos trasplante, requerimiento transfusional, periodo aplásico (neutropenia absoluta, trombocitopenia severa, anemia severa y presentación de neutropenia febril, número de células madre trasplantadas, fuente y criopreservación o no. Los resultados de las diferentes variables por medir fueron tabulados y almacenados en una base para su posterior análisis descriptivo univariado cualitativo y cuantitativo. Resultados: todos los pacientes injertaron adecuadamente. El injerto de neutrófilos ocurrió entre 11-23 días, con una media de 14.44; el injerto de plaquetas ocurrió entre 13-25 días, con una media de 16.33, y la duración de la neutropenia absoluta fue de 5-14 días, con una media de 7.28. Conclusiones: la recuperación de los pacientes fue similar a lo descrito en la literatura internacional. (Acta Med Colomb 2012; 37: 172-176.Introduction: the aim of this study was to describe the clinical and laboratory performance in autologous transplants of hematopoietic progenitor cells in a group of patients in the Hospital Militar Central in the period january 2007 to october 2010. Material and methods: we performed a retrospective descriptive study by reviewing the medical records of these patients in regard to the time of discharge from hospital after transplantation, transfusion requirement, aplastic period (absolute neutropenia, severe thrombocytopenia, severe anemia and febrile neutropenia presentation , number of transplanted stem cells, source, and whether there was or not cryopreservation

  6. [Successful long-term control of recurrent primary central nervous system anaplastic large cell lymphoma after autologous hematopoietic stem cell transplantation with concurrent whole brain and spinal cord radiotherapy].

    Science.gov (United States)

    Hiroshima, Yuki; Kaiume, Hiroko; Kirihara, Takehiko; Takeda, Wataru; Kurihara, Taro; Sato, Keijiro; Shimizu, Ikuo; Ueki, Toshimitsu; Sumi, Masahiko; Ueno, Mayumi; Ichikawa, Naoaki; Asano, Naoko; Watanabe, Masahide; Kobayashi, Hikaru

    2015-12-01

    A 24-year-old woman was hospitalized with seizures in 2002. Magnetic resonance imaging demonstrated an intraspinal mass and inhomogeneous gadolinium enhancement along the cerebrospinal meninges. Cerebrospinal fluid (CSF) cytology showed large atypical cells expressing CD2, cytoplasmic CD3, CD7, CD13 and CD30. The patient was finally diagnosed with primary central nervous system anaplastic large cell lymphoma (ALCL). She completed 5 courses of methotrexate (MTX)/ procarbazine (PCZ)/ vincristine (VCR) (MPV) chemotherapy, followed by 2 courses of high dose cytarabine (AraC) and achieved a complete remission. In 2003, she suffered from headache. CSF analysis showed atypical lymphoid cells expressing CD 30. First CNS relapse was diagnosed. She then underwent autologous peripheral blood stem cell transplantation (auto-PBSCT) after administration of thiotepa, buslfan, and cyclophosphamide. However, second CNS relapse occurred in 2004. She received 5 courses of MPV chemotherapy followed by 36 Gy of craniospinal irradiation. Although there was no recurrence of the CNS disease, a third relapse was detected in the right breast in 2009. Pathological and immunohistochemistry analysis revealed ALK-1 positive ALCL. She was treated with 6 courses of cyclophosphamide/adriamycin/vincristine/predonine (CHOP) chemotherapy and 30.6 Gy of local radiation therapy. She has remained in remission for 6 years, to date, since the last therapy and has an excellent quality of life. PMID:26725359

  7. Co-infusion of autologous adipose tissue derived neuronal differentiated mesenchymal stem cells and bone marrow derived hematopoietic stem cells, a viable therapy for post-traumatic brachial plexus injury: A case report

    Directory of Open Access Journals (Sweden)

    Umang G Thakkar

    2014-08-01

    Full Text Available Stem cell therapy is emerging as a viable approach in regenerative medicine. A 31-year-old male with brachial plexus injury had complete sensory-motor loss since 16 years with right pseudo-meningocele at C5-D1 levels and extra-spinal extension up to C7-D1, with avulsion on magnetic resonance imaging and irreversible damage. We generated adipose tissue derived neuronal differentiated mesenchymal stem cells (N-AD-MSC and bone marrow derived hematopoietic stem cells (HSC-BM. Neuronal stem cells expressed β-3 tubulin and glial fibrillary acid protein which was confirmed on immunofluorescence. On day 14, 2.8 ml stem cell inoculum was infused under local anesthesia in right brachial plexus sheath by brachial block technique under ultrasonography guidance with a 1.5-inch-long 23 gauge needle. Nucleated cell count was 2 × 10 4 /μl, CD34+ was 0.06%, and CD45-/90+ and CD45-/73+ were 41.63% and 20.36%, respectively. No untoward effects were noted. He has sustained recovery with re-innervation over a follow-up of 4 years documented on electromyography-nerve conduction velocity study.

  8. Autologous antibodies that bind neuroblastoma cells.

    Science.gov (United States)

    Sun, Yujing; Sholler, Giselle S; Shukla, Girja S; Pero, Stephanie C; Carman, Chelsea L; Zhao, Ping; Krag, David N

    2015-11-01

    Antibody therapy of neuroblastoma is promising and our goal is to derive antibodies from patients with neuroblastoma for developing new therapeutic antibodies. The feasibility of using residual bone marrow obtained for clinical indications as a source of tumor cells and a source of antibodies was assessed. From marrow samples, neuroblastoma cells were recovered, grown in cell culture and also implanted into mice to create xenografts. Mononuclear cells from the marrow were used as a source to generate phage display antibody libraries and also hybridomas. Growth of neuroblastoma patient cells was possible both in vitro and as xenografts. Antibodies from the phage libraries and from the monoclonal hybridomas bound autologous neuroblastoma cells with some selectivity. It appears feasible to recover neuroblastoma cells from residual marrow specimens and to generate human antibodies that bind autologous neuroblastoma cells. Expansion of this approach is underway to collect more specimens, optimize methods to generate antibodies, and to evaluate the bioactivity of neuroblastoma-binding antibodies. PMID:26210205

  9. Sweet Syndrome After Autologous Stem Cell Transplant.

    Science.gov (United States)

    Alkan, Ali; İdemen, Celal; Okçu Heper, Aylin; Utkan, Güngör

    2016-02-01

    Sweet syndrome (acute febrile neutrophilic dermatosis) is a rare clinical entity characterized by skin lesions, neutrophilia, fever, and neutrophilic infiltration of the dermis. It may be a consequence of malignant disease, comorbidities, or drugs. We present a case of acute febrile neutrophilic dermatosis in a patient after autologous stem cell transplant. PMID:25748978

  10. High-Dose [131I]Tositumomab (anti-CD20) Radioimmunotherapy and Autologous Hematopoietic Stem Cell Transplantation for Adults (ge) 60 Years Old with Relapsed or Refractory B-Cell Lymphoma

    International Nuclear Information System (INIS)

    Purpose: The majority of patients with relapsed or refractory B-cell, non-Hodgkin's lymphoma (NHL) are over 60 years of age, yet they are often denied potentially curative high-dose therapy and autologous stem cell transplants (ASCT) due to the risk of excessive treatment-related morbidity and mortality. Myeloablative anti-CD20 radioimmunotherapy (RIT) can deliver curative radiation doses to tumor sites while limiting exposure to normal organs and may be particularly suited for older adults requiring high-dose therapy. Methods: Patients over age 60 with relapsed B-NHL received infusions of tositumomab anti-CD20 antibody labeled with 5-10mCi I-131 tracer for dosimetry purposes followed 10 days later by individualized therapeutic infusions of I-131-tositumomab (median 525 mCi, range 328-1154 mCi) to deliver 25-27Gy to the critical normal organ receiving the highest radiation dose. ASCT was performed approximately 2 weeks after therapy. Results: Twenty-four patients with a median age of 64 (range 60-76) who had received a median of four prior regimens (range 2-14) were treated. Thirteen (54%) had chemotherapy-resistant disease. The estimated 3-year overall and progression-free survivals were 59% and 51%, respectively with a median follow-up of 2.9 years (range 1-6 years). All patients experienced expected myeloablation with engraftment of platelets ((ge) 20K/(micro)L) and neutrophils ((ge)500/(micro)L) occurring a median of 9 and 15 days, respectively following ASCT. There were no treatment-related deaths, and only two patients experienced grade 4 non-hematologic toxicity. Conclusions: Myeloablative RIT and ASCT is a safe and effective therapeutic option for older adults with relapsed B-NHL

  11. Treatment of massive gastrointestinal bleeding occurred during autologous stem cell transplantation with recombinant activated factor VII and octreotide

    Directory of Open Access Journals (Sweden)

    Erman Atas

    2015-01-01

    Full Text Available After hematopoietic stem cell transplantation (HSCT, patients may suffer from bleeding. One of the bleeding type is gastrointestinal (GI which has serious morbidity and mortality in children with limited treatment options. Herein, we presented a child with upper GI bleeding post autologous HSCT controlled successfully by using recombinant activated factor VII (rFVIIa and octreotide infusion.

  12. 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. PMID:24750320

  13. Generation of induced pluripotent stem cells as a potential source of hematopoietic stem cells for transplant in PNH patients.

    Science.gov (United States)

    Phondeechareon, Tanapol; Wattanapanitch, Methichit; U-Pratya, Yaowalak; Damkham, Chanapa; Klincumhom, Nuttha; Lorthongpanich, Chanchao; Kheolamai, Pakpoom; Laowtammathron, Chuti; Issaragrisil, Surapol

    2016-10-01

    Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic anemia caused by lack of CD55 and CD59 on blood cell membrane leading to increased sensitivity of blood cells to complement. Hematopoietic stem cell transplantation (HSCT) is the only curative therapy for PNH, however, lack of HLA-matched donors and post-transplant complications are major concerns. Induced pluripotent stem cells (iPSCs) derived from patients are an attractive source for generating autologous HSCs to avoid adverse effects resulting from allogeneic HSCT. The disease involves only HSCs and their progeny; therefore, other tissues are not affected by the mutation and may be used to produce disease-free autologous HSCs. This study aimed to derive PNH patient-specific iPSCs from human dermal fibroblasts (HDFs), characterize and differentiate to hematopoietic cells using a feeder-free protocol. Analysis of CD55 and CD59 expression was performed before and after reprogramming, and hematopoietic differentiation. Patients' dermal fibroblasts expressed CD55 and CD59 at normal levels and the normal expression remained after reprogramming. The iPSCs derived from PNH patients had typical pluripotent properties and differentiation capacities with normal karyotype. After hematopoietic differentiation, the differentiated cells expressed early hematopoietic markers (CD34 and CD43) with normal CD59 expression. The iPSCs derived from HDFs of PNH patients have normal levels of CD55 and CD59 expression and hold promise as a potential source of HSCs for autologous transplantation to cure PNH patients. PMID:27465155

  14. Experiments on Gene Transferring to Primary Hematopoietic Cells by Liposome

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Liposomes have showed many advantages in mediating exogenous gene into many cell types in vitro and in vivo. But few data are available concerning gene transfer into hematopoietic cells. In this report, we described two-marker genes (Neo R and Lac Z) co-transferred into hematopoietic cells of human and mouse by using liposome in vitro. The efficiency of gene transfer was tested by Xgal staining and observation of colony formation. The X-gal blue staining rate of transduced cells was about (13.33±2. 68) % in human and about (16. 28±2.95) % in mouse without G418 selection. After G418 selection, the blue cell rate was (46. 06±3.47)%in human and (43. 45±4. 1) % in mouse, which were markedly higher than those before selection, suggesting that high-efficiency gene transfer and expression could be attained in primary hematopoietic cells using this easy and harmless transduction protocol. At the same time, this protocol provided experimental data for clinicians to investigate the biology of marrow reconstitution and trace the origin of relapse after autologous bone marrow transplantation for the patients with leukemia.

  15. Transplante de células-tronco hematopoéticas para tumores sólidos: recomendações do Consenso Brasileiro de Transplante de Medula Óssea Autologous hematopoietic stem cell transplantation in solid tumors: the Brazilian Consensus on Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Décio Lerner

    2010-05-01

    Full Text Available O transplante de células-tronco hematopoéticas autólogo permite o escalonamento de dose de drogas quimioterápicas e é uma estratégia atraente para tratamento de tumores sólidos, principalmente em doenças recaídas. Não há, no entanto, estudos randomizados fase III que demonstrem benefício deste procedimento em tumor sólido. Em tumor germinativo de testículo, há estudos fase II com excelentes resultados, proporcionando cura para doentes refratários a platina ou que estão em terceira linha de quimioterapia. Com base nisto, o transplante de células-tronco hematopoéticas autólogo é considerado tratamento padrão para tumor germinativo recaído. Para câncer de mama, o papel desta modalidade de tratamento permanece controverso apesar dos vinte anos de experiência. Ainda é utilizado em ensaios clínicos e talvez exista algum subgrupo que se beneficie. O procedimento não oferece benefício para câncer de ovário, pulmão ou tumor cerebral. O transplante alogeneico de células-tronco hematopoéticas para tumores sólidos se baseia no efeito enxerto-contra-tumor, que é observado para algumas doenças: câncer mamário, colorretal, ovariano, pancreático e, finalmente, renal, em que há a maior experiência. Porém, o tratamento ainda é considerado experimental.Autologous hematopoietic stem cell transplantation, which allows chemotherapy dose-escalonation, is an attractive strategy for solid tumors treatment, specially relapsed diseases. However, there are no phase III trials showing benefits. There are phase II trials showing excellent results for germ cell tumors, including cure for platinrefractory and heavily pretreated patients. Because of this, autologous stem cell transplantation is considered standard of care for relapsed germ cell tumor. The role of this treatment remains controversial for breast cancer despite twenty years of experience. It’s still done in clinical trials and it may benefit a subgroup of patients. The

  16. Autologous cell sources in therapeutic vasculogenesis

    DEFF Research Database (Denmark)

    Szöke, Krisztina; Reinisch, Andreas; Østrup, Esben;

    2016-01-01

    BACKGROUND AIMS: Autologous endothelial cells are promising alternative angiogenic cell sources in trials of therapeutic vasculogenesis, in the treatment of vascular diseases and in the field of tissue engineering. A population of endothelial cells (ECs) with long-term proliferative capability...... functional assays, we wanted to evaluate the potential of these EC populations for use in clinical neovascularization. RESULTS: Global gene expression profiling of ECFCs, AT-ECs and the classical EC population, human umbilical vein ECs, showed that the EC populations clustered as unique populations, but very...

  17. Impact of autologous hematopoietic stem cell transplantation on the quality of life of type 1 diabetes mellitus patients Impacto do transplante de células-tronco hematopoéticas sobre a qualidade de vida de pacientes com diabetes mellitus tipo 1

    Directory of Open Access Journals (Sweden)

    Manoel Antônio dos Santos

    2011-01-01

    Full Text Available The present study aimed at assessing the health-related quality of life (HRQoL of patients with type 1 diabetes mellitus (DM1 submitted to autologous hematopoietic stem cell transplantation (HSCT. This study is part of a pioneering research protocol which tests the applicability of autologous hematopoietic stem cell transplantation as a new therapeutic approach to DM1. The study was conducted on 14 patients admitted to the ward of the Bone Marrow Transplantation Unit of a university hospital during the period from October 2006 to December 2007. The patients were evaluated at admission and on the occasion of the ambulatory return visit 100 days after transplantation. They answered the SF-36 quality of life questionnaire and the data were analyzed according to literature recommendations. The results showed that 100 days after transplantation the value of the patients' quality of life was higher compared to the pre-HSCT value, with significant differences in the Physical Domains (Role Limitations due to Physical Problems (p = .009, Vitality (p = .02 and Mental Health (p = .04, demonstrating significant appreciation of those domains after the procedure. The results indicate an improvement in HRQoL after HSCT. The SF-36 proved to be a useful instrument for the assessment of quality of life in patients with DM1 submitted to HSCT.Este estudo teve como objetivo avaliar a qualidade de vida relacionada à saúde (QVRS de pacientes com diabetes mellitus tipo 1 (DM1 submetidos ao Transplante de Células-Tronco Hematopoéticas (TCTH. O estudo é parte de um protocolo de pesquisa pioneiro no mundo, que testa a aplicabilidade do TCTH como nova abordagem terapêutica no DM1. Foram investigados 14 pacientes, que constituíram a população de pessoas internadas na enfermaria da Unidade de Transplante de Medula Óssea de um hospital universitário, no período de outubro de 2006 a dezembro de 2007. Os pacientes foram avaliados na admissão e no retorno

  18. Consenso expandido do BCTRIMS para o tratamento da esclerose múltipla: I. As evidências para o uso de imunossupressores, plasmaférese e transplante autólogo de células tronco The BCTRIMS Expanded Consensus on treatment of multiple sclerosis: I. The evidences for the use of immunossupressive agents, plasma exchange and autologous hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Dagoberto Callegaro

    2002-09-01

    Full Text Available O tratamento da esclerose múltipla (EM com imunossupressores teve início na década de 60. As observações laboratoriais e clínicas de que a doença tinha um caráter inflamatório induziu os clínicos a utilizarem medicamentos citostáticos e imunossupressores. Foram assim incorporados ao arsenal terapêutico da EM as drogas utilizadas em outras doenças inflamatórias sistêmicas como a artrite reumatóide e o lupus eritematoso sistêmico. As drogas imunossupressoras mais utilizadas são a ciclofosfamida, azatioprina e o metotrexate. A ciclosporina e a cladribina foram utilizadas mais recentemente para o controle da EM na forma recorrente-remitente (RR. O mitoxantrone foi aprovado pelo FDA em 2000 para as formas mais agressivas, tanto RR, como secundariamente progressiva (SP ou primariamente progressiva (PP. Outras formas de tratamento como plasmaférese e transplante autólogo de células tronco (TACT, foram inseridas neste arsenal terapêutico com suas características específicas e para casos especiais.Since the sixties immunosuppressive agents have been used in the treatment of multiple sclerosis as there was cumulating evidence of the inflammatory nature of the disease. Cyclophosphamide, azathioprine and methotrexate have been the most frequently employed drugs whereas other agents such as cyclosporine and cladribine have been recently tested for RRMS. Mithoxantrone, on the other hand, was approved by the FDA for treatment of aggressive forms of the disease. Other immunointerventions such as plasma exchange and autologous hematopoietic stem cell transplantation have recently been employed in some special circumstances. This paper analyses the most important published data on the use of the immunosuppressive agents, plasma exchange and autologous hematopoietic stem cell transplantation according to the classes of evidences and types of recommendations of these drugs and immunointerventions. It provides sufficient information to

  19. Return to the hematopoietic stem cell origin

    OpenAIRE

    Samokhvalov, Igor M.

    2012-01-01

    Studying embryonic hematopoiesis is complicated by diversity of its locations in the constantly changing anatomy and by the mobility of blood cell precursors. Embryonic hematopoietic progenitors are identified in traditional in vivo and in vitro cell potential assays. Profound epigenetic plasticity of mammalian embryonic cells combined with significant inductive capacity of the potential assays suggest that our understanding of hematopoietic ontogenesis is substantially distorted. Non-invasiv...

  20. Thrombopoietin expands hematopoietic stem cells after transplantation

    OpenAIRE

    Fox, Norma; Priestley, Greg; Papayannopoulou, Thalia; Kaushansky, Kenneth

    2002-01-01

    Multiple lines of evidence indicate that thrombopoietin (TPO) contributes to the development of hematopoietic stem cells (HSC), supporting their survival and proliferation in vitro. To determine whether TPO supports the impressive expansion of HSC observed following transplantation, we transplanted normal marrow cells into lethally irradiated Tpo–/– and Tpo+/+ mice and quantified HSC self-renewal and expansion and hematopoietic progenitor cell homing. Although essentially identical numbers of...

  1. The role of the embryonic microenvironment in hematopoietic cell development

    NARCIS (Netherlands)

    E. Haak (Esther)

    2007-01-01

    textabstractThe adult hematopoietic system is comprised of a hierarchy of cells with the hematopoietic stem cell (HSC) at its foundation. HSCs give rise to progenitors that differentiate into mature hematopoietic cells, which perform the physiological functions of the hematopoietic system. The matur

  2. Autologous rosette-forming T cells as the responding cells in human autologous mixed-lymphocyte reaction.

    OpenAIRE

    Palacios, R; Llorente, L; Alarcón-Segovia, D; Ruíz-Arguelles, A; Díaz-Jouanen, E

    1980-01-01

    Autologous rosette-forming cells (Tar cells) have surface and functional characteristics of post-thymic precursors and among these characteristics there are some that have been identified in the responsive cell of the autologous mixed-lymphocyte reaction (AMLR). We therefore did AMLR with circulating mononuclear cells from normal subjects using as responding cells either total T cells, T cells depleted of Tar cells, or purified Tar cells. The response of Tar cells in AMLR was significantly gr...

  3. The Biology of Allogeneic Hematopoietic Cell Resistance

    Science.gov (United States)

    Shizuru, Judith A.; Bhattacharya, Deepta; Cavazzana-Calvo, Marina

    2016-01-01

    At the most basic level, success of an allogeneic hematopoietic cell transplantation (HCT) procedure relies upon the engraftment of recipients with donor hematopoietic stem cells (HSCs) that will generate blood formation for the life of that individual. The formula to achieve durable HSC engraftment involves multiple factors including the recipient conditioning regimen, the nature of the genetic disparity between donor and recipient, and the content of the hematopoietic graft. Animal and clinical studies have shown that the biology of host resistance is complex, involving both immune and nonimmune elements. In this article, we review the factors that contribute to host resistance, describe emerging concepts on the basic biology of resistance, and discuss hematopoietic resistance as it relates specifically to patients with severe combined immunodeficiencies (SCID)— disorders that bring unique insights into the dynamics of cell replacement by allogeneic HSCs and progenitor cells. PMID:19913629

  4. Molecular mechanisms underlying adhesion and migration of hematopoietic stem cells

    OpenAIRE

    Sahin, Aysegul Ocal; Buitenhuis, Miranda

    2012-01-01

    Hematopoietic stem cell transplantation is the most powerful treatment modality for a large number of hematopoietic malignancies, including leukemia. Successful hematopoietic recovery after transplantation depends on homing of hematopoietic stem cells to the bone marrow and subsequent lodging of those cells in specific niches in the bone marrow. Migration of hematopoietic stem cells to the bone marrow is a highly regulated process that requires correct regulation of the expression and activit...

  5. Hematopoietic Stem Cell Transplantation—50 Years of Evolution and Future Perspectives

    OpenAIRE

    Israel Henig; Tsila Zuckerman

    2014-01-01

    Hematopoietic stem cell transplantation is a highly specialized and unique medical procedure. Autologous transplantation allows the administration of high-dose chemotherapy without prolonged bone marrow aplasia. In allogeneic transplantation, donor-derived stem cells provide alloimmunity that enables a graft-versus-tumor effect to eradicate residual disease and prevent relapse. The first allogeneic transplantation was performed by E. Donnall Thomas in 1957. Since then the field has evolved an...

  6. 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.

  7. Genetic Modification of Hematopoietic Stem Cells as a Therapy for HIV/AIDS

    Directory of Open Access Journals (Sweden)

    Patrick Younan

    2013-11-01

    Full Text Available The combination of genetic modification and hematopoietic stem cell (HSC transplantation may provide the necessary means to develop an alternative treatment option to conventional antiretroviral therapy. As HSCs give rise to all hematopoietic cell types susceptible to HIV infection, modification of HSCs is an ideal strategy for the development of infection-resistant immune cell populations. Although promising results have been obtained in multiple animal models, additional evidence is needed to convincingly demonstrate the feasibility of this approach as a treatment of HIV-1 infected patients. Here, we review the potential of HSC transplantation and the recently identified limitations of this approach. Using the Berlin Patient as a model for a functional cure, we contrast the confines of autologous versus allogeneic transplantation. Finally, we suggest that although autologous, gene-modified HSC-transplantation may significantly reduce plasma viremia, reaching the lower detection limits currently obtainable through daily HAART will remain a challenging endeavor that will require innovative combinatorial therapies.

  8. Autonomous behavior of hematopoietic stem cells

    NARCIS (Netherlands)

    Kamminga, LM; Akkerman, [No Value; Weersing, E; Ausema, A; Dontje, B; Van Zant, G; de Haan, G

    2000-01-01

    Objective. Mechanisms that affect the function of primitive hematopoietic stem cells with long-term proliferative potential remain largely unknown. Here we assessed whether properties of stem cells are cell-extrinsically or cell-autonomously regulated. Materials and Methods. We developed a model in

  9. Human hematopoietic cell culture, transduction, and analyses

    DEFF Research Database (Denmark)

    Bonde, Jesper; Wirthlin, Louisa; Kohn, Donald B;

    2008-01-01

    This unit provides methods for introducing genes into human hematopoietic progenitor cells. The Basic Protocol describes isolation of CD34(+) cells, transduction of these cells with a retroviral vector on fibronectin-coated plates, assaying the efficiency of transduction, and establishing long......-term cultures. Support protocols describe methods for maintenance of vector-producing fibroblasts (VPF) and supernatant collection from these cells, screening medium components for the ability to support hematopoietic cell growth, and establishing colonies from long-term cultures. Other protocols provide PCR...

  10. Allogeneic Hematopoietic Cell Transplantation in Patients with Myelodysplastic Syndrome and Concurrent Lymphoid Malignancy

    OpenAIRE

    Zimmerman, Zachary; Scott, Bart L.; Gopal, Ajay K.; Sandmaier, Brenda M.; Maloney, David G; Deeg, H. Joachim

    2011-01-01

    Allogeneic hematopoietic cell transplantation (HCT) can be curative for both myelodysplastic syndromes (MDS) and lymphoid malignancies. Little is known about the efficacy of allogeneic HCT in patients in whom both myeloid and lymphoid disorders are present at the time of HCT. We analyzed outcomes in 21 patients with MDS and concurrent lymphoid malignancy when undergoing allogeneic HCT. Seventeen patients had received extensive prior cytotoxic chemotherapy, including autologous HCT in seven, f...

  11. COST OF HEMATOPOIETIC STEM CELL TRANSPLANTATION IN INDIA

    Directory of Open Access Journals (Sweden)

    Sanjeev Kumar Sharma

    2014-06-01

    Full Text Available Hematopoietic stem cell transplantation (HSCT is the definite cure for many hematological diseases. With the increasing indications for HSCT and its relatively low cost in Indian subcontinent, an increasing number of patients are opting for this procedure. We retrospectively analyzed the cost of one hundred sixty two HSCTs done at our center in the last three years. The median cost of autologous transplant was INR 7,52,294 (USD, $ 12,500 (range INR 6,19,850-14,17,212 and the median cost of allogenic transplant was INR 10,74,881 ($18,000 (range INR 6,49,944-23,82,227. The cost of HSCT is cheaper here compared to that in developed countries and success rates are nearly equivalent. The major factors contributing to the cost are related to the complications post-transplant mainly infections and graft versus host disease, which are also the reasons for the increased stay in the hospital.

  12. Venous thromboembolism in hematopoietic stem cell transplant recipients.

    Science.gov (United States)

    Chaturvedi, S; Neff, A; Nagler, A; Savani, U; Mohty, M; Savani, B N

    2016-04-01

    Venous thromboembolism (VTE) is an increasingly recognized problem in the post-hematopoietic stem cell transplantation (HSCT) setting, with a lack of high-quality evidence-based data to recommend best practices. Few patients with hematologic malignancies and even fewer post-HSCT patients were included in randomized trials of VTE prophylaxis and treatment. Prior VTE, GVHD, infections and indwelling venous catheters are risk factors for thrombosis. The increasing use of post-transplant maintenance therapy with lenalidomide in patients with multiple myeloma adds to this risk after autologous HSCT. These patients are also at high risk of bleeding complications because of prolonged thrombocytopenia and managing the competing risks of bleeding and thrombosis can be challenging. This review aims to provide a practical, clinician-focused approach to the prevention and treatment of VTE in the post-HSCT setting. PMID:26691425

  13. 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.

  14. 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).

  15. Optimizing autologous cell grafts to improve stem cell gene therapy.

    Science.gov (United States)

    Psatha, Nikoletta; Karponi, Garyfalia; Yannaki, Evangelia

    2016-07-01

    Over the past decade, stem cell gene therapy has achieved unprecedented curative outcomes for several genetic disorders. Despite the unequivocal success, clinical gene therapy still faces challenges. Genetically engineered hematopoietic stem cells are particularly vulnerable to attenuation of their repopulating capacity once exposed to culture conditions, ultimately leading to low engraftment levels posttransplant. This becomes of particular importance when transduction rates are low or/and competitive transplant conditions are generated by reduced-intensity conditioning in the absence of a selective advantage of the transduced over the unmodified cells. These limitations could partially be overcome by introducing megadoses of genetically modified CD34(+) cells into conditioned patients or by transplanting hematopoietic stem cells hematopoietic stem cells with high engrafting and repopulating potential. On the basis of the lessons gained from cord blood transplantation, we summarize the most promising approaches to date of increasing either the numbers of hematopoietic stem cells for transplantation or/and their engraftability, as a platform toward the optimization of engineered stem cell grafts. PMID:27106799

  16. High-Dose Chemotherapy Followed by Autologous Stem Cell Transplantation for Metastatic Rhabdomyosarcoma—A Systematic Review

    OpenAIRE

    Frank Peinemann; Nicolaus Kröger; Carmen Bartel; Ulrich Grouven; Max Pittler; Rudolf Erttmann; Michael Kulig

    2011-01-01

    INTRODUCTION: Patients with metastatic rhabdomyosarcoma (RMS) have a poor prognosis. The aim of this systematic review is to investigate whether high-dose chemotherapy (HDCT) followed by autologous hematopoietic stem cell transplantation (HSCT) in patients with metastatic RMS has additional benefit or harm compared to standard chemotherapy. METHODS: Systematic literature searches were performed in MEDLINE, EMBASE, and The Cochrane Library. All databases were searched from inception to Februar...

  17. Clostridium difficile infection after adult autologous stem cell transplantation: A multicenter study of epidemiology and risk factors

    OpenAIRE

    Alonso, Carolyn D.; Dufresne, Simon F.; Hanna, David B.; Labbé, Annie-Claude; Treadway, Suzanne B.; Neofytos, Dionissios; Bélanger, Sylvie; Huff, Carol Ann; Laverdière, Michel; Marr, Kieren A.

    2013-01-01

    We sought to describe the epidemiology of Clostridium difficile infection (CDI) among adult recipients of autologous hematopoietic stem cell transplantation (auto HSCT) within the first year after HSCT in centers with variable epidemiology of hyper-toxigenic strains. A multicenter, retrospective nested case-control study was conducted among 873 auto HSCT recipients at Johns Hopkins Hospital (JHH, Baltimore, MD) and Hôpital Maisonneuve-Rosemont (HMR, Montreal, Canada) between 1/2003-12/2008. D...

  18. Proliferative capacity of murine hematopoietic stem cells

    International Nuclear Information System (INIS)

    The present study demonstrates a decrease in self-renewal capacity with serial transfer of murine hematopoietic stem cells. Production of differentiated cell progeny is maintained longer than stem cell self-renewal. In normal animals the capacity for self-renewal is not decreased with increasing donor age. The stem cell compartment in normal animals, both young and old, appears to be proliferatively quiescent. After apparent recovery from the alkylating agent busulfan, the probability of stem cell self-renewal is decreased, there is a permanent defect in the capacity of the bone marrow for serial transplantation, and the stem cells are proliferatively active. These findings support a model of the hematopoietic stem cell compartment as a continuum of cells with decreasing capacities for self-renewal, increasing likelihood for differentiation, and increasing proliferative activity. Cells progress in the continuum in one direction and such progression is not reversible

  19. Induction of embryonic stem cells to hematopoietic cells in vitro

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    In order to get hematopoietic cells from embryonic stem (ES) cells and to study development mechanisms of hematopoietic cells, the method of inducing embryonic stem cells to hematopoietic cells was explored by differenciating mouse ES cells and human embryonic cells in three stages. The differentiated cells were identified by flow cytometry, immunohistochemistry and Wright's staining. The results showed that embryoid bodies (EBs) could form when ES cells were cultured in the medium with 2-mercaptoethanol (2-ME). However, cytokines, such as stem cell factor (SCF), thrombopoietin (TPO), interleukin-3 (IL-3), interleukin-6 (IL-6), erythropoietin (EPO) and granular colony stimulating factor (G-CSF), were not helpful for forming EBs. SCF, TPO and embryonic cell conditional medium were useful for the differentiation of mouse EBs to hematopoietic progenitors. Eighty-six percent of these cells were CD34+ after 6-d culture. Hematopoietic progenitors differentiated to B lymphocytes when they were cocultured with primary bone marrow stroma cells in the DMEM medium with SCF and IL-6. 14 d later, most of the cells were CD34-CD38+. Wright's staining and immunohistochemistry showed that 80% of these cells were plasma-like morphologically and immunoglubolin positive. The study of hematopoietic cells from human embryonic cells showed that human embryonic cell differentiation was very similar to that of mouse ES cells. They could form EBs in the first stage and the CD34 positive cells account for about 48.5% in the second stage.

  20. Recent advances in hematopoietic stem cell biology

    DEFF Research Database (Denmark)

    Bonde, Jesper; Hess, David A; Nolta, Jan A

    2004-01-01

    made recently in the field of stem cell biology, researchers now have improved tools to define novel populations of stem cells, examine them ex vivo using conditions that promote self-renewal, track them into recipients, and determine whether they can contribute to the repair of damaged tissues......PURPOSE OF REVIEW: Exciting advances have been made in the field of hematopoietic stem cell biology during the past year. This review summarizes recent progress in the identification, culture, and in vivo tracking of hematopoietic stem cells. RECENT FINDINGS: The roles of Wnt and Notch proteins...... in regulating stem cell renewal in the microenvironment, and how these molecules can be exploited in ex vivo stem cell culture, are reviewed. The importance of identification of stem cells using functional as well as phenotypic markers is discussed. The novel field of nanotechnology is then discussed...

  1. Radiolabelled Autologous Cells: Methods and Standardization for Clinical Use

    International Nuclear Information System (INIS)

    This publication serves as a useful resource for nuclear medicine physicians, radiologists, radiopharmacists, pharmacologists and other researchers engaged with radiolabelling of autologous products for clinical application. It provides practical guidelines towards clinical work with radiolabelled autologous products and aims to streamline the variety of strategies that have evolved, for example, in the handling of radiolabelled red and white blood cells. The publication highlights the importance of the quality of radiolabelling services, provides advice on safety issues, and also addresses the use of other radiolabelled autologous products and their translation into the clinical environment

  2. Cellular memory and, hematopoietic stem cell aging

    NARCIS (Netherlands)

    Kamminga, Leonie M.; de Haan, Gerald

    2006-01-01

    Hematopoietic stem cells (HSCs) balance self-renewal and differentiation in order to sustain lifelong blood production and simultaneously maintain the HSC pool. However, there is clear evidence that HSCs are subject to quantitative and qualitative exhaustion. In this review, we briefly discuss sever

  3. 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...

  4. 单纯化疗、化疗加 DC-CIK 细胞治疗和化疗加自体造血干细胞移植治疗急性白血病疗效分析%Analysis of treating the acute leukemia in risk group with simple chemotherapy, chemotherapy + DC-CIK cell therapy, chemotherapy and autologous hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    宋庆林; 江梅

    2014-01-01

    Objective:Retrospectively analyze the clinical effect, safety and popular significance of the treatment of three kinds of immune cells in the treatment of acute leukemia in risk group with chemotherapy, chemotherapy analyzed + DC-CIK cell therapy, chemotherapy and autologous hematopoietic stem cell transplantation.Methods:65 cases of acute leukemia patients in risk group, were randomly divided into three groups, respectively treated with chemotherapy alone ( 21 cases) , chemotherapy ( chemotherapy++DC-CIK cells in the treatment of 26 cases) ,chemotherapy and autologous hematopoietic stem cell transplantation ( 18 cases) , equivalent to three groups of common data and the extent of the disease;used for a healthy ( tissue from patients with parents or children or infant umbilical cord) mononuclear cells, preparation of DC-CIK cells, each patient infusion of 4-6 times, the end of each interval after 30d. treatment to periodically review the three-year survival rates of patients, treatment costs, MDR detection, DC-CIK after injection of fever, allergies and other adverse reactions. Flow cytometry detection in patients with changes of peripheral blood lymphocyte subsets. Results:DC-CIK cells infusion injection and no occurrence of serious adverse reactions. Compared with the pure chemotherapy group, CD3+, +DC-CIK cells in vivo chemotherapy treatment for patients with CD4+, CD8+, CD56+lymphocytes were significantly higher than those before treatment level of infusion (P<0.01), the treatment group with a follow-up period of CD3+, CD4+, CD8+, CD56+ lymphocytes were significantly higher than that of chemotherapy plus autologous hematopoietic stem cell transplantation (P<0.05).Conclusion: Chemotherapy of +DC-CIK cell therapy method is better than the single chemotherapy and chemotherapy plus autologous hematopoietic stem cell transplantation. It can significantly improve the patient tumor killing T cell level, help to clear after transplantation in patients with minimal

  5. Ex vivo Expansion of Hematopoietic Stem Cells

    OpenAIRE

    Farahbakhshian, Elnaz

    2013-01-01

    textabstractHematopoiesis is a complex cellular differentiation process resulting in the formation of all blood cell types. In this process, hematopoietic stem cells (HSCs) reside at the top of the hematopoiesis hierarchy and have the capacity to differentiate into all blood cell lineages (multipotency) as well as maintaining themselves (self-renewal) during the lifespan of an individual. Mouse primitive HSCs are first found in the blood islands of the extra-embryonic yolk sac at day 7.5 of g...

  6. Autologous stem cell transplantation in the treatment of Hodgkin's disease

    OpenAIRE

    Tarabar Olivera; Tukić Ljiljana; Stamatović Dragana; Balint Bela; Elez Marija; Ostojić Gordana; Tatomirović Željka; Marjanović Slobodan

    2009-01-01

    Background/Aim. High-dose chemotherapy with autologous stem cell transplantacion (ASCT) has shown to produce long-term disease-free survival in patients with chemotherapysensitive Hodgkin disease. The aim of the study was to evaluate efficacy of ASCT in the treatment of Hodgkin's disease. Methods. Between May 1997 and September 2008, 34 patients with Hodgkin's disease in median age of 25 (range 16-60) years, underwent ASCT. Autologous SCT were performed as consolidation therapy in one poor-ri...

  7. Proteomic cornerstones of hematopoietic stem cell differentiation

    DEFF Research Database (Denmark)

    Klimmeck, Daniel; Hansson, Jenny; Raffel, Simon;

    2012-01-01

    Regenerative tissues such as the skin epidermis, the intestinal mucosa or the hematopoietic system are organized in a hierarchical manner with stem cells building the top of this hierarchy. Somatic stem cells harbor the highest self-renewal activity and generate a series of multipotent progenitors...... which differentiate into lineage committed progenitors and subsequently mature cells. In this report, we applied an in-depth quantitative proteomic approach to analyze and compare the full proteomes of ex vivo isolated and FACS-sorted populations highly enriched for either multipotent hematopoietic stem....../progenitor cells (HSPCs, Lin(neg)Sca-1(+)c-Kit(+)) or myeloid committed precursors (Lin(neg)Sca-1(-)c-Kit(+)). By employing stable isotope dimethyl labeling and high-resolution mass spectrometry, more than 5,000 proteins were quantified. From biological triplicate experiments subjected to rigorous statistical...

  8. Unrelated hematopoietic stem cell registry and the role of the Hematopoietic Stem Cell Bank

    OpenAIRE

    Beom, Su-Hee; Kim, Eung Jo; Kim, Miok; Kim, Tai-Gyu

    2016-01-01

    Background The hematopoietic stem cell bank has been actively recruiting registrants since 1994. This study systematically reviews its operations and outcomes over the last 20 years. Methods Retrospective data on a total of 47,711 registrants were reviewed. Relevant data were processed using PASW Statistics for Windows, version 18.0. Results As of 2013, the Korean Network for Organ Sharing database contained 265,307 registrants. Of these, 49,037 (18%) registrants committed to hematopoietic ce...

  9. Hematopoietic Stem Cells Contribute to Lymphatic Endothelium

    OpenAIRE

    Jiang, Shuguang; Bailey, Alexis S.; Goldman, Devorah C.; Swain, John R.; Wong, Melissa H.; Streeter, Philip R; Fleming, William H.

    2008-01-01

    Background Although the lymphatic system arises as an extension of venous vessels in the embryo, little is known about the role of circulating progenitors in the maintenance or development of lymphatic endothelium. Here, we investigated whether hematopoietic stem cells (HSCs) have the potential to give rise to lymphatic endothelial cells (LEC). Methodology/Principal Findings Following the transfer of marked HSCs into irradiated recipients, donor-derived LEC that co-express the lymphatic endot...

  10. Nonmyeloablative allogeneic hematopoietic stem cell transplantation.

    OpenAIRE

    Baron, Frédéric; Beguin, Yves

    2002-01-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) is the most effective treatment for selected hematological malignancies. Its curative potential is largely mediated by an immune-mediated destruction of malignant cells by donor lymphocytes termed graft-versus-leukemia (GVL) effect. However, because of its toxicity, conventional allogeneic HSCT is restricted to younger and fitter patients. These observations led several groups to set up new (less toxic) transplant protocols (nonmyeloab...

  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. 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. PMID:27496493

  13. Prostaglandin E2 regulates hematopoietic stem cell

    International Nuclear Information System (INIS)

    Prostaglandin E2 (PGE2) is a bioactive lipid molecule produced by cyclooxygenase (COX), which plays an important role on hematopoiesis. While it can block differentiation of myeloid progenitors but enhance proliferation of erythroid progenitors. Recent research found that PGE2 have the effects on hematopoietic stem cell (HSC) function and these effects were independent from effects on progenitor cells. Exposure of HSC cells to PGE2 in vitro can increase homing efficiency of HSC to the murine bone marrow compartment and decrease HSC apoptosis, meanwhile increase long-term stem cell engraftment. In-vivo treatment with PGE2 expands short-term HSC and engraftment in murine bone marrow but not long-term HSC.In addition, PGE2 increases HSC survival after radiation injury and enhance hematopoietic recovery, resulting maintains hematopoietic homeostasis. PGE2 regulates HSC homeostasis by reactive oxygen species and Wnt pathway. Clinical beneficial of 16, 16-dimethyl-prostaglandin E2 treatment to enhance engraftment of umbilical cord blood suggest important improvements to therapeutic strategies. (authors)

  14. Lentivirus-mediated Gene Transfer in Hematopoietic Stem Cells Is Impaired in SHIV-infected, ART-treated Nonhuman Primates

    OpenAIRE

    Younan, Patrick M; Peterson, Christopher W.; Polacino, Patricia; Kowalski, John P.; Obenza, Willimark; Miller, Hannah W.; Milless, Brian P; Gafken, Phil; DeRosa, Stephen C; Hu, Shiu-Lok; Kiem, Hans-Peter

    2015-01-01

    Recent studies have demonstrated that genetically modified hematopoietic stem cells (HSCs) can reduce HIV viremia. We have developed an HIV/AIDS-patient model in Simian/human immunodeficiency virus (SHIV)-infected pigtailed macaques that are stably suppressed on antiretroviral therapy (ART: raltegravir, emtricitabine and tenofovir). Following SHIV infection and ART, animals undergo autologous HSC transplantation (HSCT) with lentivirally transduced cluster of differentiation (CD)34+ cells expr...

  15. The biology of hematopoietic stem cells.

    Science.gov (United States)

    Szilvassy, Stephen J

    2003-01-01

    Rarely has so much interest from the lay public, government, biotechnology industry, and special interest groups been focused on the biology and clinical applications of a single type of human cell as is today on stem cells, the founder cells that sustain many, if not all, tissues and organs in the body. Granting organizations have increasingly targeted stem cells as high priority for funding, and it appears clear that the evolving field of tissue engineering and regenerative medicine will require as its underpinning a thorough understanding of the molecular regulation of stem cell proliferation, differentiation, self-renewal, and aging. Despite evidence suggesting that embryonic stem (ES) cells might represent a more potent regenerative reservoir than stem cells collected from adult tissues, ethical considerations have redirected attention upon primitive cells residing in the bone marrow, blood, brain, liver, muscle, and skin, from where they can be harvested with relative sociological impunity. Among these, it is arguably the stem and progenitor cells of the mammalian hematopoietic system that we know most about today, and their intense study in rodents and humans over the past 50 years has culminated in the identification of phenotypic and molecular genetic markers of lineage commitment and the development of functional assays that facilitate their quantitation and prospective isolation. This review focuses exclusively on the biology of hematopoietic stem cells (HSCs) and their immediate progeny. Nevertheless, many of the concepts established from their study can be considered fundamental tenets of an evolving stem cell paradigm applicable to many regenerating cellular systems. PMID:14734085

  16. Hepatic complications of allogeneic hematopoietic cell transplantation

    Directory of Open Access Journals (Sweden)

    Ramazan Idilman

    2008-09-01

    Full Text Available Hepatic complications of allogeneic hematopoietic cell transplantation contribute substantially to the overall success of the procedure and represent a major cause of morbidity and mortality. Early hepatic complications consist of the sinusoidal obstruction syndrome, drug toxicities, infections, and acute graft-versus-host disease, while late hepatic complications consist of chronic graft-versus host disease, chronic viral hepatitis, and iron overload states. Successful management of the hepatic complications of allogeneic hematopoietic cell transplantation is dependent on several factors. These include the recognition and elimination of any pre-transplant risk factors for these problems and the development of strategies to evaluate and prevent them in both the early and later post-transplant periods. The aims of the present review are 1 to identify the early and late hepatic complications of allogeneic hematopoietic cell transplantation, in the chronological order in which they occur, 2 to characterize the diagnostic procedures used to identify them, and finally 3 to present the current therapeutic approaches used to manage these problems.

  17. Indications for hematopoietic stem cell transplantation in patients with follicular lymphoma: a consensus project of the EBMT-Lymphoma Working Party.

    Science.gov (United States)

    Montoto, Silvia; Corradini, Paolo; Dreyling, Martin; Ghielmini, Michele; Kimby, Eva; López-Guillermo, Armando; Mackinnon, Stephen; Marcus, Robert E; Salles, Gilles; Schouten, Harry C; Sureda, Anna; Dreger, Peter

    2013-07-01

    The aim of this project was to define indications for hematopoietic stem cell transplantation in follicular lymphoma in Europe. In the absence of evidence-based data, a RAND-modified Delphi procedure was used by an expert panel. After pre-defining statements, these were individually/anonymously scored by each participant using a 9-point scale. Consensus was reached that: 1) high-dose therapy with autologous stem cell rescue is not an appropriate option to consolidate first remission in patients responding to immuno-chemotherapy outside clinical trials; 2) in patients with first chemo-sensitive relapse, high-dose therapy with autologous stem cell rescue is an appropriate option to consolidate remission, especially in patients with a short response after immuno-chemotherapy or with high-risk FLIPI; 3) high-dose therapy with autologous stem cell rescue is also appropriate in second/subsequent chemo-sensitive relapses; 4) allotransplant (preferably a reduced intensity conditioning-allotransplant) should be considered at relapse after high-dose therapy with autologous stem cell rescue. No consensus was reached on the role of high-dose therapy with autologous stem cell rescue in low-risk first relapse, or on when an allotransplant should be preferred over high-dose therapy with autologous stem cell rescue. In the absence of evidence-based data, the consensus method used was a valuable tool to define indications for hematopoietic stem cell transplant in follicular lymphoma. PMID:23813647

  18. Autologous bone-marrow mesenchymal cell induced chondrogenesis (MCIC).

    Science.gov (United States)

    Huh, Sung Woo; Shetty, Asode Ananthram; Ahmed, Saif; Lee, Dong Hwan; Kim, Seok Jung

    2016-01-01

    Degenerative and traumatic articular cartilage defects are common, difficult to treat, and progressive lesions that cause significant morbidity in the general population. There have been multiple approaches to treat such lesions, including arthroscopic debridement, microfracture, multiple drilling, osteochondral transplantation and autologous chondrocyte implantation (ACI) that are currently being used in clinical practice. Autologous bone-marrow mesenchymal cell induced chondrogenesis (MCIC) is a single-staged arthroscopic procedure. This method combines a modified microfracture technique with the application of a bone marrow aspirate concentrate (BMAC), hyaluronic acid and fibrin gel to treat articular cartilage defects. We reviewed the current literatures and surgical techniques for mesenchymal cell induced chondrogenesis. PMID:27489409

  19. Outcomes and costs of autologous stem cell mobilization with chemotherapy plus G-CSF versus G-CSF alone

    OpenAIRE

    Sung, Anthony D.; Grima, Daniel T; Bernard, Lisa M.; Brown, Stephen; Carrum, George; Holmberg, Leona; Horwitz, Mitchell E.; Liesveld, Jane L.; Kanda, Junya; McClune, Brian; Shaughnessy, Paul; Tricot, Guido J.; Nelson J Chao

    2013-01-01

    Chemotherapy plus granulocyte colony stimulating factor (G-CSF) (C+G) and G-CSF alone are two of the most common methods of mobilizing CD34+ cells for autologous hematopoietic stem cell transplantation (AHSCT). In order to compare and determine real-world outcomes and costs of these strategies, we performed a retrospective study of 226 consecutive patients at 11 medical centers (64 lymphoma, 162 multiple myeloma), of whom 55% and 66% received C+G. Patients with C+G collected more CD34+ cells/...

  20. Radiation response of human hematopoietic cells

    International Nuclear Information System (INIS)

    The radiosensitivity and capacity to accumulate and repair sub-lethal damage has been studied in hematopoietic cell lines of human origin and in stem cells derived from blood and bone narrow of normal human donors. The results were analysed in terms of the linear quadratic and multitarget models. For the cell lines intrinsic radiosensitivity varied widely with D/sub o/'s ranging from 0.53 to 1.39 Gy. Five of the cell lines showed same capacity to accumulate sub-lethal damage and in three of these survival was enhanced by dose fractionation or reduction of dose rate. Among the cell lines of leukemic origin, several did not conform in one or more respects with the highly radiosensitive and repair deficient model associated with hematopoietic cells. There was no apparent correlation between radiation response and the phenotype (myeloid, lymphoid or undifferentiated) of the cell lines studied. Variability of radiation response and in some cases an unpredicted degree of radioresistance and capacity to repair sub-lethal damage has now been demonstrated for both cultured and primary explants of human leukemic cells. These observations have implications for the design of Total Body Irradiation protocols for use prior to bone narrow transplant

  1. Mobilized peripheral blood grafts include more than hematopoietic stem cells: the immunological perspective.

    Science.gov (United States)

    Saraceni, F; Shem-Tov, N; Olivieri, A; Nagler, A

    2015-07-01

    Although stem cell mobilization has been performed for more than 20 years, little is known about the effects of mobilizing agents on apheresis composition and the impact of graft cell subsets on patients' outcome. With the increasing use of plerixafor and the inclusion of poor mobilizers in autologous transplant procedures, new parameters other than CD34(+) stem cell dose are emerging; plerixafor seems to mobilize more primitive CD34(+)/CD38(-) stem cells compared with G-CSF, but their correlation with stable hematopoietic engraftment is still obscure. Immune recovery is as crucial as hematopoietic reconstitution, and higher T and natural killer cells infused within the graft have been correlated with better outcome in autologous transplant; recent studies showed increased mobilization of immune effectors with plerixafor compared with G-CSF, but further data are needed to clarify the clinical impact of these findings. In the allogeneic setting, much evidence suggests that mobilized T-cell alloreactivity is tempered by G-CSF, probably with the mediation of dendritic cells, even though no clear correlation with GVL and GVHD has been found. Plerixafor is not approved in healthy donors yet; early data suggest it might mobilize a GVHD protective balance of immune effectors, but further studies are needed to define its role in allogeneic transplant. PMID:25665044

  2. Exogenous endothelial cells as accelerators of hematopoietic reconstitution

    Directory of Open Access Journals (Sweden)

    Mizer J

    2012-11-01

    Full Text Available Abstract Despite the successes of recombinant hematopoietic-stimulatory factors at accelerating bone marrow reconstitution and shortening the neutropenic period post-transplantation, significant challenges remain such as cost, inability to reconstitute thrombocytic lineages, and lack of efficacy in conditions such as aplastic anemia. A possible means of accelerating hematopoietic reconstitution would be administration of cells capable of secreting hematopoietic growth factors. Advantages of this approach would include: a ability to regulate secretion of cytokines based on biological need; b long term, localized production of growth factors, alleviating need for systemic administration of factors that possess unintended adverse effects; and c potential to actively repair the hematopoietic stem cell niche. Here we overview the field of hematopoietic growth factors, discuss previous experiences with mesenchymal stem cells (MSC in accelerating hematopoiesis, and conclude by putting forth the rationale of utilizing exogenous endothelial cells as a novel cellular therapy for acceleration of hematopoietic recovery.

  3. Clinical Allogeneic and Autologous Islet Cell Transplantation: Update

    Directory of Open Access Journals (Sweden)

    Shinichi Matsumoto

    2011-06-01

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

  4. 自体造血干细胞移植治疗1型糖尿病的疗效和安全性评价%Efficacy and safety of autologous hematopoietic stem cell transplantation in treating type 1 diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    顾卫琼; 李小英; 王卫庆; 宁光; 孙首悦; 胡炯; 唐暐; 卫静淑; 朱莉萍; 洪洁; 汤正义; 刘建民

    2010-01-01

    colony-stimulating factor and then collected from peripheral blood by leukapheresis and cryopreserved. The cells were injected intravenously after conditioning with cyclophosphamide and rabbit antithymocyte globulin. Serum levels of HbA1c, C-peptide levels, and anti-glutamic acid decarboxylase antibody (GAD-Ab)titers were measured before and after AHST. Meanwhile, adverse event was recorded.Results The average age of 18 patients (6 males and 12 females)was ( 18.8±4.4 )years, the mean follow-up was ( 414± 150 ) days. 67 % ( 12/18 ) patients became insulin free, the earliest one happened at 2 weeks after AHST, and the latest one at 6 months. 4 cases resumed insulin use because of influenza and other reasons resulting in the rise of blood glucose level. Currently, 8 patients (44.4%) were completely free of insulin therapy, and the remaining cases reduced the insulin dosage by 67.3% ±22.4%. 18 cases had lowered GAD-Ab level, the negative rate was 33.3% (6/18 ). Fasting and postprandial 2 h C-peptide levels increased significantly after A HST. Area under the curve for C-peptide ( AUCC ) increased much more markedly, and it could be maintained for 1 year. Duringtransplantation,all patients had varying degrees of gastrointestinal reactions, hair loss, fever, bone marrow suppression, and other side effects. 5 patients received blood component transfusion. No damage or other severe adverse events of heart, liver, kidney, and other organs were observed. Most side effects gradually disappeared after 2-4 weeks. The recovery of neutropenia was the slowest. Conclusion Autologous hematopoietic stem cell transplantation for treatment of newly-onset type 1 diabetes with residual islet function showed a certain effect and high safety. The widened use of this new technique should be cautious until the therapeutic mechanism has been further studied.

  5. 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...

  6. Epigenetic regulation of hematopoietic stem cell aging

    Energy Technology Data Exchange (ETDEWEB)

    Beerman, Isabel, E-mail: isabel.beerman@childrens.harvard.edu [Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138 (United States); Department of Pediatrics, Harvard Medical School, Boston, MA 02115 (United States); Program in Cellular and Molecular Medicine, Division of Hematology/Oncology, Boston Children' s Hospital, MA 02116 (United States); Rossi, Derrick J. [Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138 (United States); Department of Pediatrics, Harvard Medical School, Boston, MA 02115 (United States); Program in Cellular and Molecular Medicine, Division of Hematology/Oncology, Boston Children' s Hospital, MA 02116 (United States)

    2014-12-10

    Aging is invariably associated with alterations of the hematopoietic stem cell (HSC) compartment, including loss of functional capacity, altered clonal composition, and changes in lineage contribution. Although accumulation of DNA damage occurs during HSC aging, it is unlikely such consistent aging phenotypes could be solely attributed to changes in DNA integrity. Another mechanism by which heritable traits could contribute to the changes in the functional potential of aged HSCs is through alterations in the epigenetic landscape of adult stem cells. Indeed, recent studies on hematopoietic stem cells have suggested that altered epigenetic profiles are associated with HSC aging and play a key role in modulating the functional potential of HSCs at different stages during ontogeny. Even small changes of the epigenetic landscape can lead to robustly altered expression patterns, either directly by loss of regulatory control or through indirect, additive effects, ultimately leading to transcriptional changes of the stem cells. Potential drivers of such changes in the epigenetic landscape of aged HSCs include proliferative history, DNA damage, and deregulation of key epigenetic enzymes and complexes. This review will focus largely on the two most characterized epigenetic marks – DNA methylation and histone modifications – but will also discuss the potential role of non-coding RNAs in regulating HSC function during aging.

  7. Epigenetic regulation of hematopoietic stem cell aging

    International Nuclear Information System (INIS)

    Aging is invariably associated with alterations of the hematopoietic stem cell (HSC) compartment, including loss of functional capacity, altered clonal composition, and changes in lineage contribution. Although accumulation of DNA damage occurs during HSC aging, it is unlikely such consistent aging phenotypes could be solely attributed to changes in DNA integrity. Another mechanism by which heritable traits could contribute to the changes in the functional potential of aged HSCs is through alterations in the epigenetic landscape of adult stem cells. Indeed, recent studies on hematopoietic stem cells have suggested that altered epigenetic profiles are associated with HSC aging and play a key role in modulating the functional potential of HSCs at different stages during ontogeny. Even small changes of the epigenetic landscape can lead to robustly altered expression patterns, either directly by loss of regulatory control or through indirect, additive effects, ultimately leading to transcriptional changes of the stem cells. Potential drivers of such changes in the epigenetic landscape of aged HSCs include proliferative history, DNA damage, and deregulation of key epigenetic enzymes and complexes. This review will focus largely on the two most characterized epigenetic marks – DNA methylation and histone modifications – but will also discuss the potential role of non-coding RNAs in regulating HSC function during aging

  8. Drosophila Rabex-5 restricts Notch activity in hematopoietic cells and maintains hematopoietic homeostasis

    OpenAIRE

    Reimels, Theresa A.; Cathie M. Pfleger

    2015-01-01

    ABSTRACT Hematopoietic homeostasis requires the maintenance of a reservoir of undifferentiated blood cell progenitors and the ability to replace or expand differentiated blood cell lineages when necessary. Multiple signaling pathways function in these processes, but how their spatiotemporal control is established and their activity is coordinated in the context of the entire hematopoietic network are still poorly understood. We report here that loss of the gene Rabex-5 in Drosophila causes se...

  9. Hematopoietic potential cells in skeletal muscle

    Institute of Scientific and Technical Information of China (English)

    Atsushi Asakura

    2007-01-01

    @@ During mouse embryogenesis,the formation of primi-tive hematopoiesis begins in the yolk sac on embryonic day 7.5(E7.5).Thereafter,definitive hematopoietic stem cell(HSC)activity is first detectable in the aorta-gonad-mesonephros(AGM)region on E10,followed by fetal liver and yolk sac.Subsequently,the fetal liver by E12 becomes the main tissue for definitive hematopoiesis.At a later time,HSC population in the fetal liver migrates to the bone marrow,which becomes the maior site of he-matopoiesis throughout normal adult life[1].

  10. Mechanism of hematopoietic stem cell homing

    International Nuclear Information System (INIS)

    The clinical transplantation of hematopoietic stem cell (HSC) originating from many sources such as bone marrow, peripheral blood and cord blood has been widely applied in recent years. At the same time, the development of the study on the mechanism of HSC homing which involves multi-procedures has been achieved. And a lot of molecular and cytokines on the surface or in the microenvironment of HSC are functioning in homing. The purpose of is to review those molecular and cytokines on which more studies have been focused in the past

  11. Regeneration of Tissues and Organs Using Autologous Cells

    Energy Technology Data Exchange (ETDEWEB)

    Anthony Atala

    2010-04-28

    The Joint Commission for Health Care Organizations recently declared the shortage of transplantable organs and tissues a public health crisis. As such, there is about one death every 30 seconds due to organ failure. Complications and rejection are still significant albeit underappreciated problems. It is often overlooked that organ transplantation results in the patient being placed on an immune suppression regimen that will ultimate shorten their life span. Patients facing reconstruction often find that surgery is difficult or impossible due to the shortage of healthy autologous tissue. In many cases, autografting is a compromise between the condition and the cure that can result in substantial diminution of quality of life. The national cost of caring for persons who might benefit from engineered tissues or organs has reached $600 billion annually. Autologous tissue technologies have been developed as an alternative to transplantation or reconstructive surgery. Autologous tissues derived from the patient's own cells are capable of correcting numerous pathologies and injuries. The use of autologous cells eliminates the risks of rejection and immunological reactions, drastically reduces the time that patients must wait for lifesaving surgery, and negates the need for autologous tissue harvest, thereby eliminating the associated morbidities. In fact, the use of autologous tissues to create functional organs is one of the most important and groundbreaking steps ever taken in medicine. Although the basic premise of creating tissues in the laboratory has progressed dramatically, only a limited number of tissue developments have reached the patients to date. This is due, in part, to the several major technological challenges that require solutions. To that end, we have been in pursuit of more efficient ways to expand cells in vitro, methods to improve vascular support so that relevant volumes of engineered tissues can be grown, and constructs that can mimic the

  12. Autologous Bone Marrow Stem Cells combined with Allograft Cancellous Bone in Treatment of Nonunion

    OpenAIRE

    Le Thua Trung Hau; Duc Phu Bui; Nguyen Duy Thang; Pham Dang Nhat; Le Quy Bao; Nguyen Phan Huy; Tran Ngoc Vu; Le Phuoc Quang; Boeckx willy Denis; Mey Albert De

    2015-01-01

    Autologous cancellous bone graft is currently used as a gold standard method for treatment of bone nonunion. However, there is a limit to the amount of autologous cancellous bone that can be harvested and the donor site morbidity presents a major disadvantage to autologous bone grafting. Embedding viable cells within biological scaffolds appears to be extremely promising. The purpose of this study was to assess the outcome of autologous bone marrow stem cells combined with a cancellous bone a...

  13. Infusion of Autologous Retrodifferentiated Stem Cells into Patients with Beta-Thalassemia

    Directory of Open Access Journals (Sweden)

    Ilham Saleh Abuljadayel

    2006-01-01

    Full Text Available Beta-thalassemia is a genetic, red blood cell disorder affecting the beta-globin chain of the adult hemoglobin gene. This results in excess accumulation of unpaired alpha-chain gene products leading to reduced red blood cell life span and the development of severe anemia. Current treatment of this disease involves regular blood transfusion and adjunct chelation therapy to lower blood transfusion–induced iron overload. Fetal hemoglobin switching agents have been proposed to treat genetic blood disorders, such as sickle cell anemia and beta-thalassemia, in an effort to compensate for the dysfunctional form of the beta-globin chain in adult hemoglobin. The rationale behind this approach is to pair the excess normal alpha-globin chain with the alternative fetal gamma-chain to promote red blood cell survival and ameliorate the anemia. Reprogramming of differentiation in intact, mature, adult white blood cells in response to inclusion of monoclonal antibody CR3/43 has been described. This form of retrograde development has been termed “retrodifferentiation”, with the ability to re-express a variety of stem cell markers in a heterogeneous population of white blood cells. This form of reprogramming, or reontogeny, to a more pluripotent stem cell state ought to recapitulate early hematopoiesis and facilitate expression of a fetal and/or adult program of hemoglobin synthesis or regeneration on infusion and subsequent redifferentiation. Herein, the outcome of infusion of autologous retrodifferentiated stem cells (RSC into 21 patients with beta-thalassemia is described. Over 6 months, Infusion of 3-h autologous RSC subjected to hematopoietic-conducive conditions into patients with beta-thalassemia reduced mean blood transfusion requirement, increased mean fetal hemoglobin synthesis, and significantly lowered mean serum ferritin. This was always accompanied by an increase in mean corpuscular volume (MCV, mean corpuscular hemoglobin (MCH, and mean

  14. Carotid Repair Using Autologous Adipose-Derived Endothelial Cells

    Science.gov (United States)

    Froehlich, Harald; Gulati, Rajiv; Boilson, Barry; Witt, Tyra; Harbuzariu, Adriana; Kleppe, Laurel; Dietz, Allan B.; Lerman, Amir; Simari, Robert D.

    2009-01-01

    Background and Purpose Adipose tissue is an abundant source of endothelial cells as well as stem and progenitor cells which can develop an endothelial phenotype. It has been demonstrated that these cells have distinct angiogenic properties in vitro and in vivo. However, whether these cells have the capacity to directly improve large vessel form and function following vascular injury remains unknown. To define whether delivery of adipose-derived endothelial cells (ADECs) would improve healing of injured carotid arteries, a rabbit model of acute arterial injury was employed. Methods Autologous rabbit ADECS were generated utilizing defined culture conditions. To test the ability of ADECs to enhance carotid artery repair, cells were delivered intra-arterially following acute balloon injury. Additional delivery studies were performed following functional selection of cells prior to delivery. Results Following rabbit omental fat harvest and digestion, a proliferative, homogenous, and distinctly endothelial population of ADECs was identified. Direct delivery of autologous ADECs resulted in marked re-endothelialization 48 hours following acute vascular injury as compared to saline controls (82.2 ±26.9% vs 4.2±3.0% pADECs that were selected for their ability to take up acetylated LDL significantly improved vasoreactivity and decreased intimal formation following vascular injury. Conclusions Taken together, these data suggest that ADECs represent an autologous source of proliferative endothelial cells which demonstrate the capacity to rapidly improve re-endothelialization, improve vascular reactivity, and decrease intimal formation in a carotid artery injury model. PMID:19286583

  15. Engraftment Syndrome after Autologous Stem Cell Transplantation: An Update Unifying the Definition and Management Approach.

    Science.gov (United States)

    Cornell, Robert Frank; Hari, Parameswaran; Drobyski, William R

    2015-12-01

    Engraftment syndrome (ES) encompasses a continuum of periengraftment complications after autologous hematopoietic stem cell transplantation. ES may include noninfectious fever, skin rash, diarrhea, hepatic dysfunction, renal dysfunction, transient encephalopathy, and capillary leak features, such as noncardiogenic pulmonary infiltrates, hypoxia, and weight gain with no alternative etiologic basis other than engraftment. Given its pleiotropic clinical presentation, the transplant field has struggled to clearly define ES and related syndromes. Here, we present a comprehensive review of ES in all documented disease settings. Furthermore, we discuss the proposed risk factors, etiology, and clinical relevance of ES. Finally, our current approach to ES is included along with a proposed treatment algorithm for the management of this complication. PMID:26327628

  16. Defining Molecular Phenotypes of Mesenchymal and hematopoietic Stem Cells derived from Peripheral blood of Acute Lymphocytic Leukemia patients for regenerative stem cell therapy

    OpenAIRE

    Pravin D. Potdar; Rambhadur P Subedi

    2011-01-01

    Acute Lymphocytic Leukemia (ALL) is a clonal myeloid disorder affecting all age groups, characterized by accumulation of immature blast cells in bone marrow and in peripheral blood. Autologous Bone Marrow Transplantation is a present treatment for cure of ALL patients, which is very expensive, invasive process and may have possibility of transplantation of malignant stem cells to patients. In the present study, we hypothesized to isolate large number of normal Mesenchymal & Hematopoietic stem...

  17. Engineering Hematopoietic Stem Cells: Lessons from Development.

    Science.gov (United States)

    Rowe, R Grant; Mandelbaum, Joseph; Zon, Leonard I; Daley, George Q

    2016-06-01

    Cell engineering has brought us tantalizingly close to the goal of deriving patient-specific hematopoietic stem cells (HSCs). While directed differentiation and transcription factor-mediated conversion strategies have generated progenitor cells with multilineage potential, to date, therapy-grade engineered HSCs remain elusive due to insufficient long-term self-renewal and inadequate differentiated progeny functionality. A cross-species approach involving zebrafish and mammalian systems offers complementary methodologies to improve understanding of native HSCs. Here, we discuss the role of conserved developmental timing processes in vertebrate hematopoiesis, highlighting how identification and manipulation of stage-specific factors that specify HSC developmental state must be harnessed to engineer HSCs for therapy. PMID:27257760

  18. [High dosage chemotherapy with autologous stem cell transplantation in multiple myeloma].

    Science.gov (United States)

    Ruckser, R; Kier, P; Buxhofer, V; Kittl, E; Tatzreiter, G; Vedovelli, H; Zelenka, P; Hübl, G; Hinterberger, W

    2000-01-01

    Between 1992 and 1999 15 patients (pts.) suffering from multiple myeloma (MM) were treated with high-dose chemotherapy and consecutive autologous stem-cell transplantation (ASTx). 10/15 pts underwent two courses of ASTx (tandem- or double ASTx). So 25 ASTx were performed in these 15 pts. in total. All pts. were under 60 a. of age. 13/15 pts. received 6 cycles of chemotherapy on an average according to the VAD-protocol (Vincristin, Adriamycin, Dexamethason). Mobilisation of peripheral hematopoietic stem cells was performed with high-dose cyclophosphamide and hematopoietic growth-factors (CSFs). The conditioning protocol consisted of high-dose melphalan (200-225 mg/m2) in 24/25 ASTx. In one single case total body irradiation (TBI) plus melphalan 140 mg/m2 was used. 2/15 pts. died within 30 days from ASTx; one patient from interstitial pneumonia after TBI, and the other, who was in a very advanced stage of his disease with multiple pretreatment courses before ASTx. The overall survival (OS) was in the mean 68 months, the progression-free survival (PFS) after ASTx 21 m respectively. In pts. with MM high-dose melphalan (up to 225 mg/m2) without TBI plus ASTx is a safe and effective procedure when performed in the early course of the disease. PMID:11261278

  19. Efficacy of deferred dosing of granulocyte colony-stimulating factor in autologous hematopoietic transplantation for multiple myeloma.

    Science.gov (United States)

    Cox, J E; Campos, S; Wu, J; May, R; Liu, H; Ramos, C A; Carrum, G; Heslop, H E; Brenner, M K; Kamble, R T

    2014-02-01

    Routine administration of G-CSF following autologous hematopoietic SCT (ASCT) expedites ANC recovery and reduces hospitalization by 1-2 days; it has no impact on febrile neutropenia, infections, morbidity, mortality, event-free survival or OS. To determine whether delayed G-CSF dosage could result in equivalent ANC recovery and thereby improve cost effectiveness, we deferred the administration of G-CSF until WBC recovery had begun. A total of 117 patients with multiple myeloma received ASCT from January 2005 to September 2012. Of these, 52 were in the conventional dosing group (CGD) and received G-CSF from Day +7 for a median of five doses. In the deferred dosing group (DGD), 65 patients received G-CSF from median day 14 post transplant for a median of zero doses. There was no difference between groups in the incidence or duration of febrile neutropenia, duration of grade III mucositis, weight gain, rash, engraftment syndrome or early death (100 days). The DGD group had a significantly longer time to neutrophil engraftment than the CGD group (15 days vs 12 days; P<0.0001), a longer period of severe neutropenia (<100/μL; 8 days vs 6 days; P<0.0001), longer treatment with intravenous antibiotics (7 days vs 5 days; P=0.016) and longer hospital stay (19 days vs 17 days; P=<0.0001). Although the cost of G-CSF was lower in the DGD group (mean $308 vs $2467), the additional hospitalization raised the median total cost of ASCT in this group by 17%. There was, however, no adverse effect of deferred dosing on the rate of febrile neuropenic episodes or Day 100 survival, so that deferred dosing of G-CSF may be suitable for patients receiving ASCT as outpatients, for whom longer hospital stay would not be an offsetting cost. PMID:24096822

  20. Regulation of Hematopoietic Stem Cells by Bone Marrow Stromal Cells

    OpenAIRE

    Anthony, Bryan; Link, Daniel C.

    2013-01-01

    Hematopoietic stem cells (HSCs) reside in specialized microenvironments (niches) in the bone marrow. The stem cell niche is thought to provide signals that support key HSC properties, including self-renewal capacity and long-term multilineage repopulation ability. The stromal cells that comprise the stem cell niche and the signals that they generate that support HSC function are the subjects of intense investigation. Here we review the complex and diverse stromal cell populations that reside ...

  1. A COMPARISON OF HLA-IDENTICAL SIBLING ALLOGENEIC VERSUS AUTOLOGOUS TRANSPLANTATION FOR DIFFUSE LARGE B-CELL LYMPHOMA: A REPORT FROM THE CIBMTR

    Science.gov (United States)

    Lazarus, Hillard M.; Zhang, Mei-Jie; Carreras, Jeanette; Hayes-Lattin, Brandon M.; Ataergin, Asli Selmin; Bitran, Jacob D.; Bolwell, Brian J.; Freytes, César O.; Gale, Robert Peter; Goldstein, Steven C.; Hale, Gregory A.; Inwards, David J.; Klumpp, Thomas R.; Marks, David I.; Maziarz, Richard T.; McCarthy, Philip L.; Pavlovsky, Santiago; Rizzo, J Douglas; Shea, Thomas C.; Schouten, Harry C.; Slavin, Shimon; Winter, Jane N.; van Besien, Koen; Vose, Julie M.; Hari, Parameswaran N.

    2010-01-01

    We compared outcomes of 916 diffuse large B cell lymphoma (DLBCL) patients age ≥ 18 years undergoing first autologous (n=837) or myeloablative allogeneic hematopoietic cell transplant (HCT) (n=79) between 1995–2003 reported to the CIBMTR. Median follow-up was 81 months for allogeneic HCT vs. 60 months for autologous. Allogeneic HCT recipients were more likely to have high risk disease features including higher stage, more prior chemotherapy regimens and resistant disease. Allogeneic HCT was associated with a higher 1 year treatment-related mortality (TRM) (RR 4.88, 95% CI, 3.21–7.40, p50 years), lower performance score, chemoresistance and earlier year of transplant. In a cohort of mainly high risk DLBCL patients, upfront myeloablative allogeneic HCT while associated with increased early mortality was associated with a similar risk of disease progression compared to lower risk patients receiving autologous HCT. PMID:20053330

  2. Importance of mesenchymal stem cells in autologous fat grafting

    DEFF Research Database (Denmark)

    Trojahn Kølle, Stig-Frederik; Oliveri, Roberto S; Glovinski, Peter Viktor;

    2012-01-01

    the fat graft with adipose tissue-derived mesenchymal stem cells (ASC) before transplantation. We have reviewed original studies published on fat transplantation enriched with ASC. We found four murine and three human studies that investigated the subject after a sensitive search of publications. In...... the human studies, so-called cell assisted lipotransfer (CAL) increased the ASC concentration 2-5 times compared with non-manipulated fat grafts, which caused a questionable improvement in survival of fat grafts, compared with that of traditional lipofilling. In contrast, in two of the murine studies......Autologous fat grafting (lipofilling) enables repair and augmentation of soft tissues and is increasingly used both in aesthetic and reconstructive surgery. Autologous fat has several advantages, including biocompatibility, versatility, natural appearance, and low donor site morbidity. The main...

  3. 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.

  4. Immunological aspects of allogeneic and autologous mesenchymal stem cell therapies.

    Science.gov (United States)

    Hoogduijn, M J; Roemeling-van Rhijn, M; Korevaar, S S; Engela, A U; Weimar, W; Baan, C C

    2011-12-01

    Mesenchymal stem cells (MSCs) have potential for therapeutic application as an immunomodulatory and regenerative agent. The immunogenicity and survival of MSCs after infusion are, however, not clear and evidence suggests that allogeneic but also autologous MSCs disappear rapidly after infusion. This may be associated with the susceptibility of MSCs to lysis by natural killer (NK) cells, possibly a result of culture-induced stress. In the present study we examined whether NK cell-mediated lysis of MSCs could be inhibited by immunosuppressive drugs. Human MSCs were isolated from adipose tissue and expanded in culture. Peripheral blood mononuclear cells were activated with interleukin (IL)-2 (200 U/ml) and IL-15 (10 ng/ml) for 7 days. CD3(-)CD16(+)CD56(+) NK cells were then isolated by fluorescence-activated cell sorting and added to europium-labeled MSCs for 4 hr in the presence or absence of immunosuppressive drugs. Lysis of MSCs was determined by spectrophotometric measurement of europium release. Nonactivated NK cells were not capable of lysing MSCs. Cytokine-activated NK cells showed upregulated levels of granzyme B and perforin and efficiently lysed allogeneic and autologous MSCs. Addition of tacrolimus, rapamycin or sotrastaurin to the lysis assay did not inhibit MSC killing. Furthermore, preincubation of activated NK cells with the immunosuppressive drugs for 24 hr before exposure to MSCs had no effect on MSC lysis. Last, addition of the immunosuppressants before and during the activation of NK cells, reduced NK cell numbers but did not affect their capacity to lyse MSCs. We conclude that the immunosuppressive drugs tacrolimus, rapamycin, and sotrastaurin are not capable of inhibiting the lysis of allogeneic and autologous MSCs by activated NK cells. Other approaches to controlling lysis of MSCs should be investigated, as controlling lysis may determine the efficacy of MSC therapy. PMID:21732766

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

    OpenAIRE

    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

    2013-01-01

    Human hematopoietic cells develop within human iPSC-derived teratomas in immunodeficient mice.Co-transplantation of OP9 stromal cells along with human iPSCs increases hematopoietic specification within teratomas.

  6. Ikaros deficiency in host hematopoietic cells separates GVL from GVHD after experimental allogeneic hematopoietic cell transplantation

    OpenAIRE

    Toubai, Tomomi; Guoqing, Hou; Rossi, Corrine; Mathewson, Nathan; Oravecz-Wilson, Katherine; Cummings, Emily; Wu, Julia; Sun, Yaping; Choi, Sung; Reddy, Pavan

    2015-01-01

    The graft-versus-leukemia (GVL) effect following allogeneic hematopoietic stem cell transplantation (allo-HCT) is critical for its curative potential. Hwever, GVL is tightly linked to graft-versus-host disease (GVHD). Among hematological malignancies, acute lymphoblastic leukemia (ALL) is the most resistant to GVL, although the reasons for this remain poorly understood. Clinical studies have identified alterations in Ikaros (Ik) transcription factor as the major marker associated with poor ou...

  7. 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.

  8. Fetal liver stromal cells promote hematopoietic cell expansion

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Kun; Hu, Caihong [Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030 (China); Zhou, Zhigang [Shanghai 1st People Hospital, Shanghai Jiao Tong University, Shanghai 201620 (China); Huang, Lifang; Liu, Wenli [Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030 (China); Sun, Hanying, E-mail: shanhum@163.com [Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030 (China)

    2009-09-25

    Future application of hematopoietic stem and progenitor cells (HSPCs) in clinical therapies largely depends on their successful expansion in vitro. Fetal liver (FL) is a unique hematopoietic organ in which hematopoietic cells markedly expand in number, but the mechanisms involved remain unclear. Stromal cells (StroCs) have been suggested to provide a suitable cellular environment for in vitro expansion of HSPCs. In this study, murine StroCs derived from FL at E14.5, with a high level of Sonic hedgehog (Shh) and Wnt expression, were found to have an increased ability to support the proliferation of HSPCs. This effect was inhibited by blocking Shh signaling. Supplementation with soluble Shh-N promoted the proliferation of hematopoietic cells by activating Wnt signaling. Our findings suggest that FL-derived StroCs support proliferation of HSPCs via Shh inducing an autocrine Wnt signaling loop. The use of FL-derived StroCs and regulation of the Shh pathway might further enhance HPSC expansion.

  9. Incidence of venous thromboembolism in the setting of hematopoietic cell transplantation.

    Science.gov (United States)

    O'Hara, V J Daphne; Miller, Trent; Mehta, Rakesh; Swartzendruber, Evonne; Kiel, Patrick J

    2014-01-01

    The underlying risk of venous thromboembolism (VTE) is unclear in patients undergoing hematopoietic cell transplantation (HCT). As such, these patients should still be considered at risk for development of VTE due to factors such as their underlying malignancy and the marked inflammatory state that develops from treatment. The purpose of this study was to characterize the incidence of VTE in patients undergoing HCT. Retrospective chart review of patients from the Indiana University Stem Cell Transplant Unit treated between January 1, 2008, and May 24, 2011. Patients were older than 18 years and had undergone HCT. The primary objective was to analyze the incidence of VTE in patients undergoing autologous HCT versus allogeneic HCT. Secondary objectives included documentation of VTE treatment strategies and time to occurrence of VTE. Of the 567 patients who underwent autologous HCT, 14 developed VTE (2.5%), whereas 5 of the 180 patients who underwent allogeneic HCT developed VTE (2.8%; P = 1.000). The median time to development of VTE from admission for HCT was 12 days in the autologous HCT arm versus 19 days in the allogeneic HCT arm (P = 0.610). The most commonly used VTE treatment strategy was enoxaparin (12 out of 19 VTEs). This study illustrates that VTE does occur rarely in patients who have undergone HCT. The optimal treatment regimen in this population requires further evaluation. Until a reliable protocol for treatment and evidence for risk factors are established, providers should be vigilant for occurrence of VTE in these patients. PMID:24061558

  10. Autologous Stem Cell Transplantation in Patient with Critical Limb Ischemia

    International Nuclear Information System (INIS)

    Critical limb ischemia (CLI) is clinical manifestation of an end-stage peripheral arterial obstruction disease. Progressive ischemia leads to development of ischemic rest pain and skin defects. Early recognition, medicamentous treatment and revascularisation are standard treatment practise in these patients. However, up to 30% of patients are not eligible for endovascular or surgical revascularisation. Remaining patients are threatened with disease progression and high risk for leg amputation. Some clinical studies demonstrated, that therapeutic angio genesis with autologous stem cells therapy may be effective in ulcer healing and prevention of limb amputation. This case report describes a 47-year old male with history of one year non-healing ulcer after the third and fifth finger amputation without option of endovascular or surgical revascularisation. Patient was successfully treated with intramuscular autologous bone marrow therapy with ulcer healing and limb salvage after 12-month follow-up. (author)

  11. Optimized patient-trajectory for patients undergoing treatment with high-dose chemotherapy and autologous stem cell transplantation

    DEFF Research Database (Denmark)

    Bartels, Frederik Reith; Smith, Nicholas Simon; Gørløv, Jette Sønderskov;

    2015-01-01

    PURPOSE: Before, during and after autologous hematopoietic stem cell transplantation (HD-ASCT) patients suffer from significant loss of physical function, and experience multiple complications during and after hospitalization. Studies regarding safety and feasibility of physical exercise interven......PURPOSE: Before, during and after autologous hematopoietic stem cell transplantation (HD-ASCT) patients suffer from significant loss of physical function, and experience multiple complications during and after hospitalization. Studies regarding safety and feasibility of physical exercise...... interventions for patients undergoing treatment with HD-ASCT are missing. METHODS: Forty patients referred to HD-ASCT treatment, suffering from multiple myeloma, lymphoma or amyloidosis aged 23-70 years were enrolled in a prospective longitudinal study. The study consisted of a home-based exercise program for...... use in the ambulatory setting and supervised exercise sessions Monday to Friday for 30-40 minutes during admission. Safety of the exercise program and physical tests were assessed by using a weekly questionnaire and report of inadvertent incidences. Adherence to the home-based exercise program was...

  12. Autologous peripheral blood stem cell harvest: Collection efficiency and factors affecting it

    Directory of Open Access Journals (Sweden)

    Aseem K Tiwari

    2016-01-01

    Full Text Available Background: Harvest of hematopoietic progenitor cells via leukapheresis is being used increasingly for transplants in India. Adequate yield of cells per kilogram body weight of recipient is required for successful engraftment. Collection efficiency (CE is an objective quality parameter used to assess the quality of leukapheresis program. In this study, we calculated the CE of the ComTec cell separator (Fresenius Kabi, Germany using two different formulae (CE1 and CE2 and analyzed various patient and procedural factors, which may affect it. Materials and Methods: One hundred and one consecutive procedures in 77 autologous donors carried out over 3 years period were retrospectively reviewed. Various characteristics like gender, age, weight, disease status, hematocrit, preprocedure total leukocyte count, preprocedure CD34 positive (CD34+ cells count, preprocedure absolute CD34+ cell count and processed apheresis volume effect on CE were compared. CE for each procedure was calculated using two different formulae, and results were compared using statistical correlation and regression analysis. Results: The mean CE1 and CE2 was 41.2 and 49.1, respectively. CE2 appeared to be more accurate indicator of overall CE as it considered the impact of continued mobilization of stem cells during apheresis procedure, itself. Of all the factors affecting CE, preprocedure absolute CD34+ was the only independent factor affecting CE. Conclusion: The only factor affecting CE was preprocedure absolute CD34+ cells. Though the mean CE2 was higher than CE1, it was not statistically significant.

  13. Bone reconstruction of large defects using bone marrow derived autologous stem cells.

    Science.gov (United States)

    Lucarelli, Enrico; Donati, Davide; Cenacchi, Annarita; Fornasari, Pier Maria

    2004-04-01

    Bone is a tissue that has the ability to heal itself when fractured. Occasionally, a critical defect can be formed when part of the bone is lost or excised, in this case the bone fails to heal and requires bone reconstruction to prevent a non-union defect. Autogenous cancellous bone is the current gold standard treatment in bone loss. Because the amount of autogenous cancellous bone that can be harvested is limited, the expanding need for bone reconstruction is paired by the growth of interest in the discipline of tissue engineering. Labs worldwide are working to provide the right carrier and the right set of cells that, once retransplanted, will ensure bone repair. Several investigators have focused their attention on a subset of autologous non-hematopoietic stem/progenitor cells contained in the adult bone marrow stroma, referred to as stromal stem cells (SSC), as the appropriate cells to be transplanted. The use of autologous cells is facilitated by less stringent ethical and regulatory issues and does not require the patient to be immunologically suppressed. In pre-clinical and clinical protocols of critical defects in which SSC are employed, two approaches are mainly used: in the first, SSC are derived from bone marrow and directly introduced at the lesion site, in the second, SSC are derived from several sites and are expanded ex vivo before being implanted. Both approaches, equally correct in principle, will have to demonstrate, with definitive evidence of their efficacy, their capability of solving a critical clinical problem such as non-union. In this report we outline the difficulties of working with SSC. PMID:15062758

  14. EXERCISE in pediatric autologous stem cell transplant patients: a randomized controlled trial protocol

    Directory of Open Access Journals (Sweden)

    Chamorro-Viña Carolina

    2012-09-01

    Full Text Available Abstract Background Hematopoietic stem cell transplantation is an intensive therapy used to improve survivorship and cure various oncologic diseases. However, this therapy is associated with high mortality rates and numerous negative side-effects. The recovery of the immune system is a special concern and plays a key role in the success of this treatment. In healthy populations it is known that exercise plays an important role in immune system regulation, but little is known about the role of exercise in the hematological and immunological recovery of children undergoing hematopoietic stem cell transplant. The primary objective of this randomized-controlled trial (RCT is to study the effect of an exercise program (in- and outpatient on immune cell recovery in patients undergoing an autologous stem cell transplantation. The secondary objective is to determine if an exercise intervention diminishes the usual deterioration in quality of life, physical fitness, and the acquisition of a sedentary lifestyle. Methods This RCT has received approval from The Conjoint Health Research Ethics Board (CHREB of the University of Calgary (Ethics ID # E-24476. Twenty-four participants treated for a malignancy with autologous stem cell transplant (5 to 18 years in the Alberta Children’s Hospital will be randomly assigned to an exercise or control group. The exercise group will participate in a two-phase exercise intervention (in- and outpatient from hospitalization until 10 weeks after discharge. The exercise program includes strength, flexibility and aerobic exercise. During the inpatient phase this program will be performed 5 times/week and will be supervised. The outpatient phase will combine a supervised session with two home-based exercise sessions with the use of the Wii device. The control group will follow the standard protocol without any specific exercise program. A range of outcomes, including quantitative and functional recovery of immune system

  15. Myeloablative Chemotherapy with Autologous Stem Cell Transplant for Desmoplastic Small Round Cell Tumor

    OpenAIRE

    Forlenza, Christopher J.; Kushner, Brian H.; Nancy Kernan; Farid Boulad; Heather Magnan; Leonard Wexler; Wolden, Suzanne L.; LaQuaglia, Michael P.; Shakeel Modak

    2015-01-01

    Desmoplastic small round cell tumor (DSRCT), a rare, aggressive neoplasm, has a poor prognosis. In this prospective study, we evaluated the role of myeloablative chemotherapy, followed by autologous stem cell transplant in improving survival in DSRCT. After high-dose induction chemotherapy and surgery, 19 patients with chemoresponsive DSRCT underwent autologous stem cell transplant. Myeloablative chemotherapy consisted of carboplatin (400–700 mg/m2/day for 3 days) + thiotepa (300 mg/m2/day fo...

  16. MiR-24 promotes the survival of hematopoietic cells.

    Directory of Open Access Journals (Sweden)

    Tan Nguyen

    Full Text Available The microRNA, miR-24, inhibits B cell development and promotes myeloid development of hematopoietic progenitors. Differential regulation of cell survival in myeloid and lymphoid cells by miR-24 may explain how miR-24's affects hematopoietic progenitors. MiR-24 is reported to regulate apoptosis, either positively or negatively depending on cell context. However, no role for miR-24 in regulating cell death has been previously described in blood cells. To examine miR-24's effect on survival, we expressed miR-24 via retrovirus in hematopoietic cells and induced cell death with cytokine or serum withdrawal. We observed that miR-24 enhanced survival of myeloid and B cell lines as well as primary hematopoietic cells. Additionally, antagonizing miR-24 with shRNA in hematopoietic cells made them more sensitive to apoptotic stimuli, suggesting miR-24 functions normally to promote blood cell survival. Since we did not observe preferential protection of myeloid over B cells, miR-24's pro-survival effect does not explain its promotion of myelopoiesis. Moreover, expression of pro-survival protein, Bcl-xL, did not mimic miR-24's impact on cellular differentiation, further supporting this conclusion. Our results indicate that miR-24 is a critical regulator of hematopoietic cell survival. This observation has implications for leukemogenesis. Several miRNAs that regulate apoptosis have been shown to function as either tumor suppressors or oncogenes during leukemogenesis. MiR-24 is expressed highly in primary acute myelogenous leukemia, suggesting that its pro-survival activity could contribute to the transformation of hematopoietic cells.

  17. Human induced pluripotent stem cells on autologous feeders.

    Directory of Open Access Journals (Sweden)

    Kazutoshi Takahashi

    Full Text Available BACKGROUND: For therapeutic usage of induced Pluripotent Stem (iPS cells, to accomplish xeno-free culture is critical. Previous reports have shown that human embryonic stem (ES cells can be maintained in feeder-free condition. However, absence of feeder cells can be a hostile environment for pluripotent cells and often results in karyotype abnormalities. Instead of animal feeders, human fibroblasts can be used as feeder cells of human ES cells. However, one still has to be concerned about the existence of unidentified pathogens, such as viruses and prions in these non-autologous feeders. METHODOLOGY/PRINCIPAL FINDINGS: This report demonstrates that human induced Pluripotent Stem (iPS cells can be established and maintained on isogenic parental feeder cells. We tested four independent human skin fibroblasts for the potential to maintain self-renewal of iPS cells. All the fibroblasts tested, as well as their conditioned medium, were capable of maintaining the undifferentiated state and normal karyotypes of iPS cells. Furthermore, human iPS cells can be generated on isogenic parental fibroblasts as feeders. These iPS cells carried on proliferation over 19 passages with undifferentiated morphologies. They expressed undifferentiated pluripotent cell markers, and could differentiate into all three germ layers via embryoid body and teratoma formation. CONCLUSIONS/SIGNIFICANCE: These results suggest that autologous fibroblasts can be not only a source for iPS cells but also be feeder layers. Our results provide a possibility to solve the dilemma by using isogenic fibroblasts as feeder layers of iPS cells. This is an important step toward the establishment of clinical grade iPS cells.

  18. Application of reticulated platelets to transfusion management during autologous stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Parco S

    2012-01-01

    Full Text Available Sergio Parco, Fulvia VascottoInstitute for Maternal and Child Health – IRCCS Burlo Garofolo, Trieste, ItalyBackground: The immature (or reticulated platelet fraction (IPF is rich in nucleic acids, especially RNA, and can be used as a predictive factor for platelet recovery in platelet immunomediated consumption or in postchemotherapy myelosuppression. Our aim was to determine if transfusions with IPF-rich solutions, during autologous peripheral blood stem cell transplantation, reduce the occurrence of bleeding and hemorrhagic complications.Patients and methods: Transfusions were administered to 40 children, affected with hematological pathologies, who underwent autologous peripheral hematopoietic progenitor cell transplantation. There were two groups of 20 patients, one group treated with IPF-poor and the other with IPF-rich solutions. In the two groups, the conditioning regimen was the same for the same pathology (hematological pathologies: 14 acute lymphoblastic leukemia; twelve acute myelocytic leukemia; four non-Hodgkin's lymphoma; two Hodgkin's lymphoma; eight solid tumors. A new automated analyzer was used to quantify the IPF: the XE2100 (Sysmex, Kobe, Japan blood cell counter with upgraded software.Results: The 20 patients who received solutions with a high percentage of IPF (3%–9% of total number of infused platelets required fewer transfusions than the 20 patients who received transfusions with a low percentage of IPF (0%–1% of total number of infused platelets: 83 versus 129 (mean of number of transfusions 4.15 versus 6.45 and a significant difference was found between the two groups by using the Mann–Whitney test (P < 0.001. The prophylactic transfusions decreased from three to two per week. There was only one case of massive hemorrhage.Conclusion: The use of IPF solutions reduces the number of transfusions and bleedings after peripheral blood stem cell transplantation in pediatric patients.Keywords: children, reticulated

  19. Critical early events in hematopoietic cell seeding and engraftment.

    OpenAIRE

    Jerry Stein; Isaac Yaniv; Nadir Askenasy

    2005-01-01

    Durable hematopoietic stem cell engraftment requires efficient homing to and seeding in the recipient bone marrow. Dissection of cellular and molecular mechanisms by retrospective analysis of functional engraftment studies imposes severe limitations on the understanding of the early stages of this process. We have established an experimental approach for in vivo functional imaging of labeled cells at the level of recipient bone marrow in real time. The adhesive interaction of hematopoietic ce...

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Immunisation of colorectal cancer patients with autologous tumour cells

    DEFF Research Database (Denmark)

    Diederichsen, Axel Cosmus Pyndt; Stenholm, A C; Kronborg, O; Fenger, C; Jensenius, Jens Christian; Zeuthen, J; Kristensen, T; Christensen, P B

    1998-01-01

    Patients with colorectal cancer were entered into a clinical phase I trial of immunotherapy with an autologous tumour cell/bacillus Calmette-Guerin (BCG) vaccine. We attempted to describe the possible effects and side effects of the immunisation, and further to investigate whether expression of...... immune-response-related surface molecules on the tumour cells in the vaccine correlated with survival. The first and second vaccine comprised of 107 irradiated tumour cells mixed with BCG, the third of irradiated tumour cells only. Thirty-nine patients were considered, but only 6 patients fulfilled the...... criteria for inclusion. No serious side effects were observed. With three years of observation time, two patients are healthy, while the rest have had recurrence, and two of them have died. In all vaccines, all tumour cells expressed HLA class I, some expressed HLA class II and none expressed CD80. There...

  2. Fertility issues following hematopoietic stem cell transplantation.

    Science.gov (United States)

    Tichelli, André; Rovó, Alicia

    2013-08-01

    With the improvement of the outcome, the number of long-term survivors of hematopoietic stem cell transplantation (HSCT) is continuously increasing. However, there is still a high burden of late morbidity and mortality. Two-thirds of the transplant survivors develop at least one late effect interfering with their physical or psychological health. Infertility is common after myeloablative HSCT conditioned with total body irradiation and high doses of gonadotoxic drugs. Other factors, such as the age of the patient at transplantation, the treatment modality received before HSCT or the onset of chronic graft versus host disease, may play an additional role. Accordingly, the number of pregnancies observed after HSCT is very low when compared to a general population in childbearing age. Furthermore, complications during pregnancy and at delivery occur significantly more frequently, probably because of the uterine damages caused by irradiation therapy. However, there is no excess of congenital abnormalities observed among newborn children. Today there are good possibilities for fertility preservation. In male patients cryopreservation of sperm, and in female patients cryopreservation of fertilized embryos or of mature oocytes, are well-established treatment options. Patients' and physicians' attitude toward discussion on fertility issues play a key role in the success of fertility preservation after HSCT. PMID:23991924

  3. Hematopoietic stem cell transplantation: clinical use and perspectives

    OpenAIRE

    Francisco Barriga; Pablo Ramírez; Angélica Wietstruck; Nicolás Rojas

    2012-01-01

    Hematopoietic stem cell transplantation is the accepted therapy of choice for a variety of malignant and non-malignant diseases in children and adults. Initially developed as rescue therapy for a patient with cancer after high doses of chemotherapy and radiation as well as the correction of severe deficiencies in the hematopoietic system, it has evolved into an adoptive immune therapy for malignancies and autoimmune disorders. The procedure has helped to obtain key information about the bone ...

  4. Circulation and chemotaxis of fetal hematopoietic stem cells.

    OpenAIRE

    Christensen, Julie L.; Wright, Douglas E.; Wagers, Amy J.; Weissman, Irving L.

    2004-01-01

    The major site of hematopoiesis transitions from the fetal liver to the spleen and bone marrow late in fetal development. To date, experiments have not been performed to evaluate functionally the migration and seeding of hematopoietic stem cells (HSCs) during this period in ontogeny. It has been proposed that developmentally timed waves of HSCs enter the bloodstream only during distinct windows to seed the newly forming hematopoietic organs. Using competitive reconstitution assays to measure ...

  5. Development of a high-titer retrovirus producer cell line capable of gene transfer into rhesus monkey hematopoietic stem cells

    International Nuclear Information System (INIS)

    Retroviral-mediated gene transfer into primitive hematopoietic cells has been difficult to achieve in large-animal models. The authors have developed an amphotropic producer clone that generates >1010 recombinant retroviral particles (colony-forming units) per ml of culture medium. Autologous rhesus monkey bone marrow cells were cocultured with either high or low titer producer clones for 4-6 days and reinfused into sublethally irradiated animals. The proviral genome was detected in blood and bone-marrow cells from all three animals reconstituted with cells cocultured with the high-titer producer cells. In contrast, three animals reconstituted with bone marrow cocultured with the low-titer producer clone exhibited no evidence of gene transfer

  6. Auto-mobilized adult hematopoietic stem cells advance neovasculature in diabetic retinopathy of mice

    Institute of Scientific and Technical Information of China (English)

    TIAN Bei; LI Xiao-xin; SHEN Li; ZHAO Min; YU Wen-zhen

    2010-01-01

    Background Hematopoietic stem cells (HSCs) can be used to deliver functionally active angiostatic molecules to the retinal vasculature by targeting active astrocytes and may be useful in targeting pre-angiogenic retinal lesions. We sought to determine whether HSC mobilization can ameliorate early diabetic retinopathy in mice.Methods Mice were devided into four groups: normal mice control group, normal mice HSC-mobilized group, diabetic mice control group and diabetic mice HSC mobilized group. Murine stem cell growth factor (murine SCF) and recombined human granulocyte colony stimulating factor (rhG-csf) were administered to the mice with diabetes and without diabetes for continuous 5 days to induce autologous HSCs mobilization, and subcutaneous injection of physiological saline was used as control. Immunohistochemical double staining was conducted with anti-mouse rat CD31 monoclonal antibody and anti-BrdU rat antibody.Results Marked HSCs clearly increased after SCF plus G-csf-mobilization. Non-mobilized diabetic mice showed more HSCs than normal mice (P=0.032), and peripheral blood significantly increased in both diabetic and normal mice (P=0.000).Diabetic mice showed more CD31 positive capillary vessels (P=0.000) and accelerated endothelial cell regeneration. Only diabetic HSC-mobilized mice expressed both BrdU and CD31 antigens in the endothelial cells of new capillaries.Conclusion Auto-mobilized adult hematopoietic stem cells advance neovasculature in diabetic retinopathy of mice.

  7. High dose ionizing irradiation induces an early and transient increase in peripheral blood hematopoietic progenitor cells; L`exposition aigue aux radiations ionisantes induit un recrutement transitoire des progeniteurs hematopoietiques au niveau du sang peripherique: implications therapeutiques potentielles

    Energy Technology Data Exchange (ETDEWEB)

    Drouet, M.; Mathieu, J.; Grenier, N.; Vetillard, J.; Chauvelot, F.; Thierry, D.; Mestries, J.C.; Herodin, F. [Centre de Recherches du Service de Sante des Armees, La Tronche, 38 - Grenoble (France)]|[Centre de Recherches du Service de Sante des Armees - Centre d`Etudes Nucleaires de Fontenay-aux-Roses, 92 (France)

    1997-12-31

    Nonhuman primates exposed to ionizing radiation exhibit an early and transient increase in peripheral blood committed hematopoietic progenitor cells. The management of bone marrow aplasia secondary to accidental irradiation could be based in part on the re-infusion of those circulating autologous progenitors following a period of ex vivo expansion with cytokines. (authors)

  8. Pulmonary heart valve replacement using stabilized acellular xenogeneic scaffolds; effects of seeding with autologous stem cells

    Directory of Open Access Journals (Sweden)

    Harpa Marius Mihai

    2015-12-01

    Full Text Available Background: We hypothesized that an ideal heart valve replacement would be acellular valve root scaffolds seeded with autologous stem cells. To test this hypothesis, we prepared porcine acellular pulmonary valves, seeded them with autologous adipose derived stem cells (ADSCs and implanted them in sheep and compared them to acellular valves.

  9. Prostaglandin E2 increases hematopoietic stem cell survival and accelerates hematopoietic recovery after radiation injury

    OpenAIRE

    Porter, Rebecca L.; Georger, Mary; Bromberg, Olga; McGrath, Kathleen E.; Frisch, Benjamin J.; Becker, Michael W.; Calvi, Laura M.

    2013-01-01

    Hematopoietic stem and progenitor cells (HSPCs), which continuously maintain all mature blood cells, are regulated within the marrow microenvironment. We previously reported that pharmacologic treatment of naïve mice with prostaglandin E2 (PGE2) expands HSPCs. However, the cellular mechanisms mediating this expansion remain unknown. Here we demonstrate that PGE2 treatment in naïve mice inhibits apoptosis of HSPCs without changing their proliferation rate. In a murine model of sub-lethal total...

  10. Clinical-scale laser-based scanning and processing of live cells: selective photothermal killing of fluorescent tumor targets for autologous stem cell transplantation

    Science.gov (United States)

    Koller, Manfred R.; Hanania, Elie G.; Eisfeld, Timothy; O'Neal, Robert A.; Khovananth, Kevin M.; Palsson, Bernhard O.

    2001-04-01

    High-dose chemotherapy, followed by autologous hematopoietic stem cell (HSC) transplantation, is widely used for the treatment of cancer. However, contaminating tumor cells within HSC harvests continue to be of major concern since re-infused tumor cells have proven to contribute to disease relapse. Many tumor purging methods have been evaluated, but all leave detectable tumor cells in the transplant and result in significant loss of HSCs. These shortcomings cause engraftment delays and compromise the therapeutic value of purging. A novel approach integrating automated scanning cytometry, image analysis, and selective laser-induced killing of labeled cells within a cell mixture is described here. Non-Hodgkin's lymphoma (NHL) cells were spiked into cell mixtures, and fluorochrome-conjugated antibodies were used to label tumor cells within the mixture. Cells were then allowed to settle on a surface, and as the surface was scanned with a fluorescence excitation source, a laser pulse was fired at every detected tumor cell using high-speed beam steering mirrors. Tumor cells were selectively killed with little effect on adjacent non-target cells, demonstrating the feasibility of this automated cell processing approach. This technology has many potential research and clinical applications, one example of which is tumor cell purging for autologous HSC transplantation.

  11. Cytokine signaling for proliferation, survival, and death in hematopoietic cells.

    Science.gov (United States)

    Miyajima, A; Ito, Y; Kinoshita, T

    1999-04-01

    The survival, proliferation, and differentiation of hematopoietic cells are regulated by cytokines. In the absence of cytokines, hematopoietic cells not only stop proliferation, but undergo apoptosis. This strict dependency of hematopoietic cells on cytokines is an important mechanism that maintains the homeostasis of blood cells. Cytokines induce various intracellular signaling pathways by activating the receptor-associated Janus kinases (Jaks), and distinct signals are responsible for cell cycle progression and cell survival. Induction of signals for cell cycle progression without suppressing apoptosis results in apoptotic cell death, indicating the essential role of anti-apoptotic signaling for cell growth. In hematopoietic cells, Ras, a cellular protooncogen product, and phosphatidylinositol 3 kinase are involved in the suppression of apoptosis. Cytokine depletion not only turns off anti-apoptotic signaling, but also actively induces cell death by activating caspases, a distinct family of cysteine proteases. Alterations in the mechanisms of cytokine signaling for cell cycle progression and anti-apoptotic function are implicated in hematological disorders. PMID:10222650

  12. SECOND AUTOLOGOUS STEM CELL TRANSPLANTATION FOR RELAPSED LYMPHOMA AFTER A PRIOR AUTOLOGOUS TRANSPLANT

    Science.gov (United States)

    Smith, Sonali M.; van Besien, Koen; Carreras, Jeanette; Bashey, Asad; Cairo, Mitchell S.; Freytes, Cesar O.; Gale, Robert Peter; Hale, Gregory A.; Hayes-Lattin, Brandon; Holmberg, Leona A.; Keating, Armand; Maziarz, Richard T.; McCarthy, Philip L.; Navarro, Willis H.; Pavlovsky, Santiago; Schouten, Harry C.; Seftel, Matthew; Wiernik, Peter H.; Vose, Julie M.; Lazarus, Hillard M.; Hari, Parameswaran

    2012-01-01

    We determined treatment-related mortality (TRM), progression free survival (PFS), and overall survival (OS) after a second autologous HCT (HCT2) for patients with lymphoma relapse after a prior HCT (HCT1). Outcomes for patients with either Hodgkin lymphoma (HL, n=21) or non-Hodgkin lymphoma (NHL, n=19) receiving HCT2 reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) were analyzed. The median age at HCT2 was 38 years (range, 16–61) and 22 (58%) patients had a Karnofsky performance score less than 90. HCT2 was performed >1 year after HCT1 in 82%. The probability of TRM at day 100 was 15% (95% CI, 3–22%). The 1, 3 and 5 yr probabilities of PFS were 50% (95% CI, 34–66%), 36% (95% CI, 21–52%) and 30% (95% CI, 16–46%), respectively. Corresponding probabilities of survival were 65% (95% CI, 50–79%), 36% (95% CI, 22–52%) and 30% (95% CI, 17–46%), respectively. At a median follow up of 72 months (range, 12–124 months) after HCT2, 29 patients (73%) have died, 18 (62%) secondary to relapsed lymphoma. The outcomes of patients with HL and NHL were similar. In summary, this series represents the largest reported group of patients with relapsed lymphomas undergoing SCT2 following failed SCT1, and with long-term follow-up. Our series suggests that SCT2 is feasible in patients relapsing after prior HCT1, with a lower TRM than that reported for allogeneic transplant in this setting. HCT2 should be considered for patients with relapsed HL or NHL after HCT1 without alternative allogeneic stem cell transplant options. PMID:18640574

  13. Oral Complications in Hematopoietic Stem Cell Recipients: The Role of Inflammation

    Directory of Open Access Journals (Sweden)

    T. M. Haverman

    2014-01-01

    Full Text Available Hematopoietic stem cell transplantation (HSCT is widely used as a potentially curative treatment for patients with various hematological malignancies, bone marrow failure syndromes, and congenital immune deficiencies. The prevalence of oral complications in both autologous and allogeneic HSCT recipients remains high, despite advances in transplant medicine and in supportive care. Frequently encountered oral complications include mucositis, infections, oral dryness, taste changes, and graft versus host disease in allogeneic HSCT. Oral complications are associated with substantial morbidity and in some cases with increased mortality and may significantly affect quality of life, even many years after HSCT. Inflammatory processes are key in the pathobiology of most oral complications in HSCT recipients. This review article will discuss frequently encountered oral complications associated with HSCT focusing on the inflammatory pathways and inflammatory mediators involved in their pathogenesis.

  14. The cost of hematopoietic stem cell transplantation in the real world.

    Science.gov (United States)

    Seber, Adriana

    2012-04-01

    In Brazil, the majority of the population does not have private health insurance and the government provides universal health care. Our 'Unique Healthcare System' pays for 95% of the 1500 hematopoietic stem cell transplants (HSCT) performed in the country every year. Hospitals are reimbursed a flat rate, ranging from US$ 13,000 for autologous to US$ 40,500 for unrelated donor transplants, excluding expenses with donor search and acquisition of the graft. The actual cost of the procedure is not captured routinely. Because unrelated donor recipients may have many clinical complications, most HSCT centers offer few or no beds to perform such transplants. The Pediatric Oncology Institute - GRAACC - is a non-profit organization that provides comprehensive care at no cost to the families, including unrelated donor HSCT. We are evaluating retrospectively the unrelated donor transplant costs to have data to present to the health authorities, looking for an appropriate funding formula for HSCT. PMID:22507822

  15. HLA-mismatched hematopoietic stem cell tranplantation for pediatric solid tumors

    Directory of Open Access Journals (Sweden)

    Andrea Pession

    2011-06-01

    Full Text Available Even if the overall survival of children with cancer is significantly improved over these decades, the cure rate of high-risk pediatric solid tumors such as neuroblastoma, Ewing’s sarcoma family tumors or rhabdomiosarcoma remain challenging. Autologous hematopoietic stem cell transplantation (HSCT allows chemotherapy dose intensification beyond marrow tolerance and has become a fundamental tool in the multimodal therapeutical approach of these patients. Anyway this procedure does not allow to these children an eventfree survival approaching more than 50% at 5 years. New concepts of allogeneic HSCT and in particular HLA-mismatched HSCT for high risk solid tumors do not rely on escalation of chemo therapy intensity and tumor load reduction but rather on a graft-versus-tumor effect. We here report an experimental study design of HLA-mismatched HSCT for the treatment of pediatric solid tumors and the inherent preliminary results.

  16. An ethical framework for the disposal of autologous stem cells.

    Science.gov (United States)

    Petrini, Carlo

    2013-01-01

    The disposal of haematopoietic stem cells stored for autologous transplantation purposes becomes a problem for hospitals when the conditions for their preservation cease to exist. When these cells have been stored for a considerable time the problem often becomes an ethical one involving informed consent and is linked to at least two simultaneous circumstances: (i) the indications regarding disposal contained in available informed consent papers are either absent or too generic; (ii) the person who provided the sample can no longer be traced. This article proposes and discusses some of the ethical criteria for addressing this problem on the basis of the so-called "principles" of North American bioethics, and compares them with some of the principles and values proposed in other models of bioethics. PMID:23412868

  17. Identification of a Hematopoietic Cell Dedifferentiation-Inducing Factor.

    Science.gov (United States)

    Li, Yunyuan; Adomat, Hans; Guns, Emma Tomlinson; Hojabrpour, Payman; Duronio, Vincent; Curran, Terry-Ann; Jalili, Reza Baradar; Jia, William; Delwar, Zahid; Zhang, Yun; Elizei, Sanam Salimi; Ghahary, Aziz

    2016-06-01

    It has long been realized that hematopoietic cells may have the capacity to trans-differentiate into non-lymphohematopoietic cells under specific conditions. However, the mechanisms and the factors for hematopoietic cell trans-differentiation remain unknown. In an in vitro culture system, we found that using a conditioned medium from proliferating fibroblasts can induce a subset of hematopoietic cells to become adherent fibroblast-like cells (FLCs). FLCs are not fibroblasts nor other mesenchymal stromal cells, based on their expression of type-1 collagen, and other stromal cell marker genes. To identify the active factors in the conditioned medium, we cultured fibroblasts in a serum-free medium and collected it for further purification. Using the fractions from filter devices of different molecular weight cut-offs, and ammonium sulfate precipitation collected from the medium, we found the active fraction is a protein. We then purified this fraction by using fast protein liquid chromatography (FPLC) and identified it by mass spectrometer as macrophage colony-stimulating factor (M-CSF). The mechanisms of M-CSF-inducing trans-differentiation of hematopoietic cells seem to involve a tyrosine kinase signalling pathway and its known receptor. The FLCs express a number of stem cell markers including SSEA-1 and -3, OCT3/4, NANOG, and SOX2. Spontaneous and induced differentiation experiments confirmed that FLCs can be further differentiated into cell types of three germ layers. These data indicate that hematopoietic cells can be induced by M-CSF to dedifferentiate to multipotent stem cells. This study also provides a simple method to generate multipotent stem cells for clinical applications. J. Cell. Physiol. 231: 1350-1363, 2016. © 2015 Wiley Periodicals, Inc. PMID:26529564

  18. Therapeutic approaches of hematopoietic syndrome after serious accidental global irradiation. Ex vivo expansion interest of hematopoietic cells

    International Nuclear Information System (INIS)

    Aplasia is one of the main syndrome, appearing after one global accidental irradiation by one ionizing radiation source. The hematopoietic syndrome is characterized by a peripheric blood cell number fall; the cell marrow is reduced too

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

    OpenAIRE

    Ana Belen Alvarez Palomo; Michaela Lucas; Dilley, Rodney J.; Samuel McLenachan; Fred Kuanfu Chen; Jordi Requena; Marti Farrera Sal; Andrew Lucas; Inaki Alvarez; Dolores Jaraquemada; Michael J. Edel

    2014-01-01

    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 rege...

  20. Granulomatous amebic encephalitis following hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Ninh Doan

    2015-01-01

    Conclusion: The authors report the third case of GAE after autologous stem cell transplant, and the ninth case overall after HSCT. This case is unusual due to its rapid clinical presentation after HSCT compared to prior literature. The case highlights the need for high suspicion of Acanthamoeba infection in this patient population.

  1. Plerixafor for autologous stem-cell mobilization and transplantation for patients in Ontario

    Science.gov (United States)

    Kouroukis, C.T.; Varela, N.P.; Bredeson, C.; Kuruvilla, J.; Xenocostas, A.

    2016-01-01

    Background High-dose chemotherapy with autologous stem-cell transplantation (asct) is an accepted part of standard therapy for patients with hematologic malignancies. Usually, stem-cell mobilization uses granulocyte colony–stimulating factor (g-csf); however, some patients are not able to be mobilized with chemotherapy and g-csf, and such patients could be at higher risk of failing mobilization. Plerixafor is a novel mobilization agent that is absorbed quickly after subcutaneous injection and, at the recommended dose of 0.24 mg/kg, provides a sustained increase in circulating CD34+ cells for 10–18 hours. The main purpose of the present report was to evaluate the most current evidence on the efficacy of plerixafor in enhancing hematopoietic stem-cell mobilization and collection before asct for patients in Ontario so as to make recommendations for clinical practice and to assist Cancer Care Ontario in decision-making with respect to this intervention. Methods The medline and embase databases were systematically searched for evidence from January 1996 to March 2015, and the best available evidence was used to draft recommendations relevant to the efficacy of plerixafor in enhancing hematopoietic stem-cell mobilization and collection before asct. Final approval of this practice guideline report was obtained from both the Stem Cell Transplant Steering Committee and the Report Approval Panel of the Program in Evidence-Based Care. Recommendations These recommendations apply to adult patients considered for asct: ■ Adding plerixafor to g-csf is an option for initial mobilization in patients with non-Hodgkin lymphoma or multiple myeloma who are eligible for asct when chemotherapy cannot be used and only g-csf mobilization is available.■ For patients with a low peripheral blood CD34+ cell count (for example, <10/μL) at the time of anticipated stem-cell harvesting, or with an inadequate first-day apheresis collection, it is recommended that plerixafor be added to the

  2. The Genetic Landscape of Hematopoietic Stem Cell Frequency in Mice

    Directory of Open Access Journals (Sweden)

    Xiaoying Zhou

    2015-07-01

    Full Text Available Prior efforts to identify regulators of hematopoietic stem cell physiology have relied mainly on candidate gene approaches with genetically modified mice. Here we used a genome-wide association study (GWAS strategy with the hybrid mouse diversity panel to identify the genetic determinants of hematopoietic stem/progenitor cell (HSPC frequency. Among 108 strains, we observed ∼120- to 300-fold variation in three HSPC populations. A GWAS analysis identified several loci that were significantly associated with HSPC frequency, including a locus on chromosome 5 harboring the homeodomain-only protein gene (Hopx. Hopx previously had been implicated in cardiac development but was not known to influence HSPC biology. Analysis of the HSPC pool in Hopx−/− mice demonstrated significantly reduced cell frequencies and impaired engraftment in competitive repopulation assays, thus providing functional validation of this positional candidate gene. These results demonstrate the power of GWAS in mice to identify genetic determinants of the hematopoietic system.

  3. Tritium contamination of hematopoietic stem cells alters long-term hematopoietic reconstitution

    International Nuclear Information System (INIS)

    Purpose: In vivo effects of tritium contamination are poorly documented. Here, we study the effects of tritiated Thymidine ([3H] Thymidine) or tritiated water (HTO) contamination on the biological properties of hematopoietic stem cells (HSC). Materials and methods: Mouse HSC were contaminated with concentrations of [3H] Thymidine ranging from 0.37-37.03 kBq/ml or of HTO ranging from 5-50 kBq/ml. The biological properties of contaminated HSC were studied in vitro after HTO contamination and in vitro and in vivo after [3H] Thymidine contamination. Results: Proliferation, viability and double-strand breaks were dependent on [3H] Thymidine or HTO concentrations used for contamination but in vitro myeloid differentiation of HSC was not affected by [3H] Thymidine contamination. [3H] Thymidine contaminated HSC showed a compromised long-term capacity of hematopoietic reconstitution and competition experiments showed an up to two-fold decreased capacity of contaminated HSC to reconstitute hematopoiesis. These defects were not due to impaired homing in bone marrow but to an initial decreased proliferation rate of HSC. Conclusion: These results indicate that contaminations of HSC with doses of tritium that do not result in cell death, induce short-term effects on proliferation and cell cycle and long-term effects on hematopoietic reconstitution capacity of contaminated HSC. (authors)

  4. 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.

  5. Reconstitution of the myeloid and lymphoid compartments after the transplantation of autologous and genetically modified CD34(+) bone marrow cells, following gamma irradiation in cynomolgus macaques

    International Nuclear Information System (INIS)

    Prolonged, altered hematopoietic reconstitution is commonly observed in patients undergoing myelo-ablative conditioning and bone marrow and/or mobilized peripheral blood-derived stem cell transplantation. We studied the reconstitution of myeloid and lymphoid compartments after the transplantation of autologous CD34+ bone marrow cells following gamma irradiation in cynomolgus macaques. The bone marrow cells were first transduced ex vivo with a lentiviral vector encoding eGFP, with a mean efficiency of 72% ± 4%. The vector used was derived from the simian immunodeficiency lentivirus SIVmac251, VSV-g pseudo-typed and encoded eGFP under the control of the phosphoglycerate kinase promoter. After myeloid differentiation, GFP was detected in colony-forming cells (37% ± 10%). A previous study showed that transduction rates did not differ significantly between colony-forming cells and immature cells capable of initiating long-term cultures, indicating that progenitor cells and highly immature hematopoietic cells were transduced with similar efficiency. Blood cells producing eGFP were detected as early as three days after transplantation,and eGFP-producing granulocyte and mononuclear cells persisted for more than one year in the periphery. Conclusion: The transplantation of CD34+ bone marrow cells had beneficial effects for the ex vivo proliferation and differentiation of hematopoietic progenitors, favoring reconstitution of the T-and B-lymphocyte, thrombocyte and red blood cell compartments. (authors)

  6. Hematopoietic Stem Cell Transplantation—50 Years of Evolution and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Israel Henig

    2014-10-01

    Full Text Available Hematopoietic stem cell transplantation is a highly specialized and unique medical procedure. Autologous transplantation allows the administration of high-dose chemotherapy without prolonged bone marrow aplasia. In allogeneic transplantation, donor-derived stem cells provide alloimmunity that enables a graft-versus-tumor effect to eradicate residual disease and prevent relapse. The first allogeneic transplantation was performed by E. Donnall Thomas in 1957. Since then the field has evolved and expanded worldwide. New indications beside acute leukemia and aplastic anemia have been constantly explored and now include congenital disorders of the hematopoietic system, metabolic disorders, and autoimmune disease. The use of matched unrelated donors, umbilical cord blood units, and partially matched related donors has dramatically extended the availability of allogeneic transplantation. Transplant-related mortality has decreased due to improved supportive care, including better strategies to prevent severe infections and with the incorporation of reduced-intensity conditioning protocols that lowered the toxicity and allowed for transplantation in older patients. However, disease relapse and graft-versus-host disease remain the two major causes of mortality with unsatisfactory progress. Intense research aiming to improve adoptive immunotherapy and increase graft-versus-leukemia response while decreasing graft-versus-host response might bring the next breakthrough in allogeneic transplantation. Strategies of graft manipulation, tumor-associated antigen vaccinations, monoclonal antibodies, and adoptive cellular immunotherapy have already proved clinically efficient. In the following years, allogeneic transplantation is likely to become more complex, more individualized, and more efficient.

  7. DNA Damage Response in Hematopoietic Stem Cell Ageing.

    Science.gov (United States)

    Li, Tangliang; Zhou, Zhong-Wei; Ju, Zhenyu; Wang, Zhao-Qi

    2016-06-01

    Maintenance of tissue-specific stem cells is vital for organ homeostasis and organismal longevity. Hematopoietic stem cells (HSCs) are the most primitive cell type in the hematopoietic system. They divide asymmetrically and give rise to daughter cells with HSC identity (self-renewal) and progenitor progenies (differentiation), which further proliferate and differentiate into full hematopoietic lineages. Mammalian ageing process is accompanied with abnormalities in the HSC self-renewal and differentiation. Transcriptional changes and epigenetic modulations have been implicated as the key regulators in HSC ageing process. The DNA damage response (DDR) in the cells involves an orchestrated signaling pathway, consisting of cell cycle regulation, cell death and senescence, transcriptional regulation, as well as chromatin remodeling. Recent studies employing DNA repair-deficient mouse models indicate that DDR could intrinsically and extrinsically regulate HSC maintenance and play important roles in tissue homeostasis of the hematopoietic system. In this review, we summarize the current understanding of how the DDR determines the HSC fates and finally contributes to organismal ageing. PMID:27221660

  8. DNA Damage Response in Hematopoietic Stem Cell Ageing

    Institute of Scientific and Technical Information of China (English)

    Tangliang Li; Zhong-Wei Zhou; Zhenyu Ju; Zhao-Qi Wang

    2016-01-01

    Maintenance of tissue-specific stem cells is vital for organ homeostasis and organismal longevity. Hematopoietic stem cells (HSCs) are the most primitive cell type in the hematopoietic system. They divide asymmetrically and give rise to daughter cells with HSC identity (self-renewal) and progenitor progenies (differentiation), which further proliferate and differentiate into full hematopoietic lineages. Mammalian ageing process is accompanied with abnormalities in the HSC self-renewal and differentiation. Transcriptional changes and epigenetic modulations have been implicated as the key regulators in HSC ageing process. The DNA damage response (DDR) in the cells involves an orchestrated signaling pathway, consisting of cell cycle regulation, cell death and senescence, transcriptional regulation, as well as chromatin remodeling. Recent studies employ-ing DNA repair-deficient mouse models indicate that DDR could intrinsically and extrinsically reg-ulate HSC maintenance and play important roles in tissue homeostasis of the hematopoietic system. In this review, we summarize the current understanding of how the DDR determines the HSC fates and finally contributes to organismal ageing.

  9. Hematopoietic stem cell transplantation with conditioning regimens containing melphalan in pediatric patients with acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    A multicenter comparative study was carried out to investigate the efficacy and safety of hematopoietic stem cell transplantation with conditioning regimens containing melphalan in pediatric patients with acute lymphoblastic leukemia. One hundred twenty three patients at a variety of remission stages were eligible for study participation. Eighty-nine were transplanted with allogeneic grafts and 34 patients with autologous grafts (23 cases with bone marrow and 11 cases with peripheral blood stem cells). Conditioning regimens used were as follows: melphalan and busulfan for 40 patients, melphalan, busulfan and TBI for 44 patients, other regimens for 39 patients. To accelerate engraftment G-CSF (lenograstim) was administered as a 1-hour or 24-hour drip infusion daily at 5 μg/kg from day 5 until hematological recovery. The five year disease free survival (DFS) was 63% for 42 patients at CR1, 41% for 41 patients at CR2 and 33% for 40 patients at other stages. There was no significant difference in the DFS between allogeneic-transplantation and autologous-transplantation in all disease stages. In patients at remission stage for CR1 and CR2, the 5-year DFS by conditioning regimen was 63% for regimen with melphalan and busulfan, 54% for regimen with melphalan, busulfan and TBI and 54% for regimens with melphalan and TBI. There was no significant difference in the DFS between the groups. Serious complications such as renal failure were observed in 11%, veno-occlusive disease in 9%, and interstitial pneumonia in 9%. The most dominating cause of death was relapse in the disease (48% of deaths) which was most commonly observed in autologous transplantation. Contrary to that, treatment related toxic death was the most frequent cause of deaths in allogeneic-transplantation. (author)

  10. Hematopoietic stem cell transplantation with conditioning regimens containing melphalan in pediatric patients with acute lymphoblastic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Matsuyama, Takaharu; Kato, Koji [Nagoya First Red Cross Hospital (Japan). Children' s Medical Center; Hanada, Ryoji [Saitama Children' s Medical Center, Iwatsuki (Japan)] [and others

    2002-07-01

    A multicenter comparative study was carried out to investigate the efficacy and safety of hematopoietic stem cell transplantation with conditioning regimens containing melphalan in pediatric patients with acute lymphoblastic leukemia. One hundred twenty three patients at a variety of remission stages were eligible for study participation. Eighty-nine were transplanted with allogeneic grafts and 34 patients with autologous grafts (23 cases with bone marrow and 11 cases with peripheral blood stem cells). Conditioning regimens used were as follows: melphalan and busulfan for 40 patients, melphalan, busulfan and TBI for 44 patients, other regimens for 39 patients. To accelerate engraftment G-CSF (lenograstim) was administered as a 1-hour or 24-hour drip infusion daily at 5 {mu}g/kg from day 5 until hematological recovery. The five year disease free survival (DFS) was 63% for 42 patients at CR1, 41% for 41 patients at CR2 and 33% for 40 patients at other stages. There was no significant difference in the DFS between allogeneic-transplantation and autologous-transplantation in all disease stages. In patients at remission stage for CR1 and CR2, the 5-year DFS by conditioning regimen was 63% for regimen with melphalan and busulfan, 54% for regimen with melphalan, busulfan and TBI and 54% for regimens with melphalan and TBI. There was no significant difference in the DFS between the groups. Serious complications such as renal failure were observed in 11%, veno-occlusive disease in 9%, and interstitial pneumonia in 9%. The most dominating cause of death was relapse in the disease (48% of deaths) which was most commonly observed in autologous transplantation. Contrary to that, treatment related toxic death was the most frequent cause of deaths in allogeneic-transplantation. (author)

  11. Autologous transplantation of amniotic fluid-derived mesenchymal stem cells into sheep fetuses

    OpenAIRE

    Shaw, S. W. Steven; Bollini, Sveva; Nader, Khalil Abi; Gastadello, Annalisa; Mehta, Vedanta; Filppi, Elisa; Cananzi, Mara; Gaspar, H. Bobby; Qasim, Waseem; Coppi, Paolo; David, Anna L.

    2011-01-01

    Long-term engraftment and phenotype correction has been difficult to achieve in humans after in utero stem cell transplantation mainly because of allogeneic rejection. Autologous cells could be obtained during gestation from the amniotic fluid with minimal risk for the fetus and the mother. Using a sheep model, we explored the possibility of using amniotic fluid mesenchymal stem cells (AFMSCs) for autologous in utero stem cell/gene therapy. We collected amniotic fluid (AF) under ultrasound-gu...

  12. Disseminated Fusarium infection in autologous stem cell transplant recipient

    OpenAIRE

    Vivian Iida Avelino-Silva; Jessica Fernandes Ramos; Fabio Eudes Leal; Leonardo Testagrossa; Yana Sarkis Novis

    2015-01-01

    Disseminated infection by Fusariumis a rare, frequently lethal condition in severely immunocompromised patients, including bone marrow transplant recipients. However, autologous bone marrow transplant recipients are not expected to be at high risk to develop fusariosis. We report a rare case of lethal disseminated Fusariuminfection in an autologous bone marrow transplant recipient during pre-engraftment phase.

  13. Mobilization of hematopoietic progenitor cells in patients with liver cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Ursula; M; Gehling; Marc; Willems; Kathleen; Schlagner; Ralf; A; Benndorf; Maura; Dandri; Jrg; Petersen; Martina; Sterneck; Joerg-Matthias; Pollok; Dieter; K; Hossfeld; Xavier; Rogiers

    2010-01-01

    AIM:To test the hypothesis that liver cirrhosis is associated with mobilization of hematopoietic progenitor cells. METHODS:Peripheral blood samples from 72 patients with liver cirrhosis of varying etiology were analyzed by flow cytometry.Identified progenitor cell subsets were immunoselected and used for functional assays in vitro. Plasma levels of stromal cell-derived factor-1(SDF-1) were measured using an enzyme linked immunosorbent assay.RESULTS:Progenitor cells with a CD133 + /CD45 + CD14 + phenotype we...

  14. Up-Front Autologous Stem-Cell Transplantation in Peripheral T-Cell Lymphoma

    DEFF Research Database (Denmark)

    d'Amore, Francesco; Relander, Thomas; Lauritzsen, Grete F; Jantunen, Esa; Hagberg, Hans; Anderson, Harald; Holte, Harald; Osterborg, Anders; Merup, Mats; Brown, Peter De Nully; Kuittinen, Outi; Erlanson, Martin; Ostenstad, Bjørn; Fagerli, Unn-Merete; Gadeberg, Ole Vestergaard; Sundström, Christer; Delabie, Jan; Ralfkiaer, Elisabeth; Vornanen, Martine; Toldbod, Helle

    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...

  15. Cell therapy of hip osteonecrosis with autologous bone marrow grafting

    Directory of Open Access Journals (Sweden)

    Hernigou Philippe

    2009-01-01

    Full Text Available Background: One of the reasons for bone remodeling leading to an insufficient creeping substitution after osteonecrosis in the femoral head may be the small number of progenitor cells in the proximal femur and the trochanteric region. Because of this lack of progenitor cells, treatment modalities should stimulate and guide bone remodeling to sufficient creeping substitution to preserve the integrity of the femoral head. Core decompression with bone graft is used frequently in the treatment of osteonecrosis of the femoral head. In the current series, grafting was done with autologous bone marrow obtained from the iliac crest of patients operated on for early stages of osteonecrosis of the hip before collapse with the hypothesis that before stage of subchondral collapse, increasing the number of progenitor cells in the proximal femur will stimulate bone remodeling and creeping substitution and thereby improve functional outcome. Materials and Methods: Between 1990 and 2000, 342 patients (534 hips with avascular osteonecrosis at early stages (Stages I and II were treated with core decompression and autologous bone marrow grafting obtained from the iliac crest of patients operated on for osteonecrosis of the hip. The percentage of hips affected by osteonecrosis in this series of 534 hips was 19% in patients taking corticosteroids, 28% in patients with excessive alcohol intake, and 31% in patients with sickle cell disease. The mean age of the patients at the time of decompression and autologous bone marrow grafting was 39 years (range: 16-61 years. The aspirated marrow was reduced in volume by concentration and injected into the femoral head after core decompression with a small trocar. To measure the number of progenitor cells transplanted, the fibroblast colony forming unit was used as an indicator of the stroma cell activity. Results: Patients were followed up from 8 to 18 years. The outcome was determined by the changes in the Harris hip score

  16. Hematopoietic stem cell transplantation in the treatment of multiple myeloma

    OpenAIRE

    Maiolino Angelo

    2002-01-01

    Multiple myeloma is a malignant clonal plasma cell disorder that accounts for about 10% of all hematological malignancies. Conventional melphalan-based chemotherapy produces less than 5% of complete remission rates, with less than 5% of patients surviving 10 years or more. The VAD regimen is very effective to induce cytoreduction, but does not prolong event free survival or overall survival. High-dose therapy with autologous bone marrow or peripheral blood stem cell support induces complete r...

  17. A new image of the hematopoietic stem cell vascular niche

    OpenAIRE

    Silberstein, Leslie E.; Lin, Charles P.

    2013-01-01

    The microenvironment within the bone marrow that maintains hematopoietic stem cell (HSC) quiescence is the subject of intense study. In a recent Nature paper, Kunisaki et al combine imaging techniques and computational modeling to define a novel arteriolar niche for quiescent HSCs within the bone marrow.

  18. 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...

  19. 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...

  20. Lentiviral hematopoietic stem cell gene therapy in inherited metabolic disorders

    NARCIS (Netherlands)

    G. Wagemaker (Gerard)

    2014-01-01

    textabstractAfter more than 20 years of development, lentiviral hematopoietic stem cell gene therapy has entered the stage of initial clinical implementation for immune deficiencies and storage disorders. This brief review summarizes the development and applications, focusing on the lysosomal enzyme

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

    DEFF Research Database (Denmark)

    Uhlving, Hilde Hylland; Larsen Bang, Cæcilie; Christensen, Ib Jarle; Buchvald, Frederik Fouirnaies; Nielsen, Kim Gjerum; Heilmann, Carsten Johan; Müller, Klaus Gottlob

    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...

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

    DEFF Research Database (Denmark)

    Kornblit, Brian; Enevold, Christian; Wang, Tao; Spellman, Stephen; Haagenson, Mike; Lee, Stephanie J; Müller, Klaus

    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...... of TLR8 rs3764879 of the donor is associated with outcome after myeloablative conditioned allogeneic HCT....

  3. Phase 1 studies of central memory-derived CD19 CAR T-cell therapy following autologous HSCT in patients with B-cell NHL.

    Science.gov (United States)

    Wang, Xiuli; Popplewell, Leslie L; Wagner, Jamie R; Naranjo, Araceli; Blanchard, M Suzette; Mott, Michelle R; Norris, Adam P; Wong, ChingLam W; Urak, Ryan Z; Chang, Wen-Chung; Khaled, Samer K; Siddiqi, Tanya; Budde, Lihua E; Xu, Jingying; Chang, Brenda; Gidwaney, Nikita; Thomas, Sandra H; Cooper, Laurence J N; Riddell, Stanley R; Brown, Christine E; Jensen, Michael C; Forman, Stephen J

    2016-06-16

    Myeloablative autologous hematopoietic stem cell transplantation (HSCT) is a mainstay of therapy for relapsed intermediate-grade B-cell non-Hodgkin lymphoma (NHL); however, relapse rates are high. In phase 1 studies designed to improve long-term remission rates, we administered adoptive T-cell immunotherapy after HSCT, using ex vivo-expanded autologous central memory-enriched T cells (TCM) transduced with lentivirus expressing CD19-specific chimeric antigen receptors (CARs). We present results from 2 safety/feasibility studies, NHL1 and NHL2, investigating different T-cell populations and CAR constructs. Engineered TCM-derived CD19 CAR T cells were infused 2 days after HSCT at doses of 25 to 200 × 10(6) in a single infusion. In NHL1, 8 patients safely received T-cell products engineered from enriched CD8(+) TCM subsets, expressing a first-generation CD19 CAR containing only the CD3ζ endodomain (CD19R:ζ). Four of 8 patients (50%; 95% confidence interval [CI]: 16-84%) were progression free at both 1 and 2 years. In NHL2, 8 patients safely received T-cell products engineered from enriched CD4(+) and CD8(+) TCM subsets and expressing a second-generation CD19 CAR containing the CD28 and CD3ζ endodomains (CD19R:28ζ). Six of 8 patients (75%; 95% CI: 35-97%) were progression free at 1 year. The CD4(+)/CD8(+) TCM-derived CD19 CAR T cells (NHL2) exhibited improvement in expansion; however, persistence was ≤28 days, similar to that seen by others using CD28 CARs. Neither cytokine release syndrome nor delayed hematopoietic engraftment was observed in either trial. These data demonstrate the safety and feasibility of CD19 CAR TCM therapy after HSCT. Trials were registered at www.clinicaltrials.gov as #NCT01318317 and #NCT01815749. PMID:27118452

  4. Treatment of Oral Mucositis in Hematologic Patients Undergoing Autologous or Allogeneic Transplantation of Peripheral Blood Stem Cells: a Prospective, Randomized Study with a Mouthwash Containing Camelia Sinensis Leaf Extract

    OpenAIRE

    Giovanni Carulli; Melania Rocco; Alessia Panichi; Chiara Feira Chios; Ester Ciurli; Chiara Mannucci; Elisabetta Sordi; Francesco Caracciolo; Federico Papineschi; Edoardo Benedetti; Mario Petrini

    2013-01-01

    Oral mucositis is an important side effect of hematopoietic stem cell transplantation (HCST), mainly due to toxicity of conditioning regimens. It produces significant pain and morbidity. The present study reports a prospective, randomized, non-blinded study testing the efficacy of a new mouthwash, called Baxidil Onco® (Sanitas Farmaceutici Srl, Tortona, Italy) in 60 hematologic patients undergoing HCST (28 autologous, 32 allogeneic). Baxidil Onco®, used three times a day from Day -1 to Day +3...

  5. Imaging of complications from hematopoietic stem cell transplant

    OpenAIRE

    Tarun Pandey; Suresh Maximin; Puneet Bhargava

    2014-01-01

    Stem cell transplant has been the focus of clinical research for a long time given its potential to treat several incurable diseases like hematological malignancies, diabetes mellitus, and neuro-degenerative disorders like Parkinson disease. Hematopoietic stem cell transplantation (HSCT) is the oldest and most widely used technique of stem cell transplant. HSCT has not only been used to treat hematological disorders including hematological malignancies, but has also been found useful in tream...

  6. Clostridium difficile infection in Chilean patients submitted to hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Javier Pilcante

    2015-12-01

    Full Text Available ABSTRACT Introduction: Patients submitted to hematopoietic stem cell transplantation have an increased risk of Clostridium difficile infection and multiple risk factors have been identi- fied. Published reports have indicated an incidence from 9% to 30% of transplant patients however to date there is no information about infection in these patients in Chile. Methods: A retrospective analysis was performed of patients who developed C. difficile infection after hematopoietic stem cell transplantations from 2000 to 2013. Statistical analysis used the Statistical Package for the Social Sciences software. Results: Two hundred and fifty patients were studied (mean age: 39 years; range: 17-69, with 147 (59% receiving allogeneic transplants and 103 (41% receiving autologous trans- plants. One hundred and ninety-two (77% patients had diarrhea, with 25 (10% cases of C. difficile infection being confirmed. Twenty infected patients had undergone allogeneic trans- plants, of which ten had acute lymphoblastic leukemia, three had acute myeloid leukemia and seven had other diseases (myelodysplastic syndrome, chronic myeloid leukemia, severe aplastic anemia. In the autologous transplant group, five patients had C. difficile infection; two had multiple myeloma, one had amyloidosis, one had acute myeloid leukemia and one had germinal carcinoma. The overall incidence of C. difficile infection was 4% within the first week, 6.4% in the first month and 10% in one year, with no difference in overall survival between infected and non-infected groups (72.0% vs. 67.6%, respectively; p-value = 0.56. Patients infected after allogeneic transplants had a slower time to neutrophil engraftment compared to non-infected patients (17.5 vs. 14.9 days, respectively; p-value = 0.008. In the autologous transplant group there was no significant difference in the neutrophil engraftment time between infected and non-infected patients (12.5 days vs. 11.8 days, respectively; p

  7. The Hematopoietic Stem Cell Niche—Home for Friend and Foe?

    OpenAIRE

    Daniela S Krause; Scadden, David T.; Preffer, Frederic I.

    2012-01-01

    The hematopoietic stem cell (HSC) niche is involved in the maintainance and regulation of quiescence, self-renewal and differentiation of hematopoietic stem cells and the fate of their progeny in mammals dealing with the daily stresses to the hematopoietic system. From the discovery that perturbations of the HSC niche can lead to hematopoietic disorders, we have now arrived at the prospect that the HSC niche may play a role in hematological malignancies and that this HSC niche may be a target...

  8. 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)

  9. Application of autologous tumor cell vaccine and NDV vaccine in treatment of tumors of digestive traet

    OpenAIRE

    Liang, Wei; Wang, Hui; Sun, Tie-Mie; Yao, Wen-Qing; Chen, Li-Li; Jin, Yu; Chun-ling LI; Meng, Fan-Juan

    2003-01-01

    AIM: To treat patients with stage I-IV malignant tumors of digestive tract using autologous tumor cell vaccine and NDV (Newcastle disease virus) vaccine, and observe the survival period and curative effect.

  10. 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.

  11. Flow cytometry data analysis of CD34+/CD133+ stem cells in bone marrow and peripheral blood and T, B, and NK cells after hematopoietic grafting.

    Science.gov (United States)

    Jaime-Pérez, José C; Villarreal-Villarreal, César D; Vázquez-Garza, Eduardo; Méndez-Ramírez, Nereida; Salazar-Riojas, Rosario; Gómez-Almaguer, David

    2016-06-01

    This article provides flow cytometry information regarding levels of expression for hematopoietic stem cell markers CD34 and CD133 obtained simultaneously of the bone marrow and peripheral blood from recipients of allogeneic and autologous transplants of PB hematoprogenitors for treating hematological malignancies and who were clinically healthy after ≥100 days following the procedure. CD34 and CD133 expression is compared regarding type of transplant (autologous vs. allogeneic) and sample cell source (bone marrow vs. peripheral blood). Patients were conditioned with a reduced-intensity conditioning regimen. Also shown is the flow cytometry analysis of mononuclear cell and lymphocyte populations in the peripheral blood of both types of recipients, as well as the characterization of immune cells, including T lymphocyte antigenic make up markers CD3, CD4 and CD8, B lymphocytes and NK cells, including total NK, bright and dim subtypes in the peripheral blood of both types of recipients. For further information and discussion regarding interpretation and meaning of post-transplant flow cytometry analysis, please refer to the article "Assessment of immune reconstitution status in recipients of a successful hematopoietic stem cell transplant from peripheral blood after reduced intensity conditioning" [1]. PMID:27115030

  12. 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.

  13. Critical early events in hematopoietic cell seeding and engraftment.

    Directory of Open Access Journals (Sweden)

    Jerry Stein

    2005-12-01

    Full Text Available Durable hematopoietic stem cell engraftment requires efficient homing to and seeding in the recipient bone marrow. Dissection of cellular and molecular mechanisms by retrospective analysis of functional engraftment studies imposes severe limitations on the understanding of the early stages of this process. We have established an experimental approach for in vivo functional imaging of labeled cells at the level of recipient bone marrow in real time. The adhesive interaction of hematopoietic cells with the bone marrow stroma evolves as the most important early event. Adhesion to the marrow, rather than the vascular endothelium, determines the efficiency of both homing and seeding, and is absolutely essential to maintain cell viability in the marrow. Seeding and engraftment may be improved either by bypassing homing or by localized transplant of a large number of cells in a relatively small marrow space. There is functional redundancy in the molecular pathways that mediate the cell-stroma interaction, such that blockage of a single pathway has only minor effect on homing and seeding. We hypothesize that successfully seeding-engrafting cells undergo extensive phenotypic changes as a consequence of interaction with the stroma, without engaging in rapid proliferation. Surprisingly, Fas-ligand appears to promote hematopoietic cell engraftment by immunomodulatory and trophic effects.

  14. Pharmacological inhibition of EGFR signaling enhances G-CSF-induced hematopoietic stem cell mobilization.

    Science.gov (United States)

    Ryan, Marnie A; Nattamai, Kalpana J; Xing, Ellen; Schleimer, David; Daria, Deidre; Sengupta, Amitava; Köhler, Anja; Liu, Wei; Gunzer, Matthias; Jansen, Michael; Ratner, Nancy; Le Cras, Timothy D; Waterstrat, Amanda; Van Zant, Gary; Cancelas, Jose A; Zheng, Yi; Geiger, Hartmut

    2010-10-01

    Mobilization of hematopoietic stem and progenitor cells (HSPCs) from bone marrow into peripheral blood by the cytokine granulocyte colony-stimulating factor (G-CSF) has become the preferred source of HSPCs for stem cell transplants. However, G-CSF fails to mobilize sufficient numbers of stem cells in up to 10% of donors, precluding autologous transplantation in those donors or substantially delaying transplant recovery time. Consequently, new regimens are needed to increase the number of stem cells in peripheral blood upon mobilization. Using a forward genetic approach in mice, we mapped the gene encoding the epidermal growth factor receptor (Egfr) to a genetic region modifying G-CSF-mediated HSPC mobilization. Amounts of EGFR in HSPCs inversely correlated with the cells' ability to be mobilized by G-CSF, implying a negative role for EGFR signaling in mobilization. In combination with G-CSF treatment, genetic reduction of EGFR activity in HSPCs (in waved-2 mutant mice) or treatment with the EGFR inhibitor erlotinib increased mobilization. Increased mobilization due to suppression of EGFR activity correlated with reduced activity of cell division control protein-42 (Cdc42), and genetic Cdc42 deficiency in vivo also enhanced G-CSF-induced mobilization. Our findings reveal a previously unknown signaling pathway regulating stem cell mobilization and provide a new pharmacological approach for improving HSPC mobilization and thereby transplantation outcomes. PMID:20871610

  15. Regeneration of Tissues and Organs Using Autologous Cells

    Energy Technology Data Exchange (ETDEWEB)

    Anthony Atala, M D

    2012-10-11

    The proposed work aims to address three major challenges to the field of regenerative medicine: 1) the growth and expansion of regenerative cells outside the body in controlled in vitro environments, 2) supportive vascular supply for large tissue engineered constructs, and 3) interactive biomaterials that can orchestrate tissue development in vivo. Toward this goal, we have engaged a team of scientists with expertise in cell and molecular biology, physiology, biomaterials, controlled release, nanomaterials, tissue engineering, bioengineering, and clinical medicine to address all three challenges. This combination of resources, combined with the vast infrastructure of the WFIRM, have brought to bear on projects to discover and test new sources of autologous cells that can be used therapeutically, novel methods to improve vascular support for engineered tissues in vivo, and to develop intelligent biomaterials and bioreactor systems that interact favorably with stem and progenitor cells to drive tissue maturation. The Institute's ongoing programs are aimed at developing regenerative medicine technologies that employ a patient's own cells to help restore or replace tissue and organ function. This DOE program has provided a means to solve some of the vexing problems that are germane to many tissue engineering applications, regardless of tissue type or target disease. By providing new methods that are the underpinning of tissue engineering, this program facilitated advances that can be applied to conditions including heart disease, diabetes, renal failure, nerve damage, vascular disease, and cancer, to name a few. These types of conditions affect millions of Americans at a cost of more than $400 billion annually. Regenerative medicine holds the promise of harnessing the body's own power to heal itself. By addressing the fundamental challenges of this field in a comprehensive and focused fashion, this DOE program has opened new opportunities to treat

  16. Erythropoietin guides multipotent hematopoietic progenitor cells toward an erythroid fate

    Science.gov (United States)

    Grover, Amit; Mancini, Elena; Moore, Susan; Mead, Adam J.; Atkinson, Deborah; Rasmussen, Kasper D.; O’Carroll, Donal; Jacobsen, Sten Eirik W.

    2014-01-01

    The erythroid stress cytokine erythropoietin (Epo) supports the development of committed erythroid progenitors, but its ability to act on upstream, multipotent cells remains to be established. We observe that high systemic levels of Epo reprogram the transcriptomes of multi- and bipotent hematopoietic stem/progenitor cells in vivo. This induces erythroid lineage bias at all lineage bifurcations known to exist between hematopoietic stem cells (HSCs) and committed erythroid progenitors, leading to increased erythroid and decreased myeloid HSC output. Epo, therefore, has a lineage instructive role in vivo, through suppression of non-erythroid fate options, demonstrating the ability of a cytokine to systematically bias successive lineage choices in favor of the generation of a specific cell type. PMID:24493804

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    of leukocyte adhesion deficiency who underwent hematopoietic stem-cell transplantation between 1993 and 2007 was retrospectively analyzed. Data were collected by the registries of the European Society for Immunodeficiencies/European Group for Blood and Marrow Transplantation, and the Center for International......, with full donor engraftment in 17 cases, mixed multilineage chimerism in 7 patients, and mononuclear cell-restricted chimerism in an additional 3 cases. CONCLUSIONS: Hematopoietic stem-cell transplantation offers long-term benefit in leukocyte adhesion deficiency and should be considered as an early...... 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....

  18. Hematopoietic Stem Cell Targeting with Surface-Engineered Lentiviral Vectors

    OpenAIRE

    sprotocols

    2014-01-01

    Authors: Els Verhoeyen and Francois-Loic Cosset Adapted from [*Gene Transfer: Delivery and Expression of DNA and RNA*](http://www.cshlpress.com/link/genetrnp.htm) (eds. Friedmann and Rossi). CSHL Press, Cold Spring Harbor, NY, USA, 2007. ### INTRODUCTION In the protocol presented here, hematopoietic stem cells (HSCs) are specifically transduced with a vector displaying the HSC-activating polypeptides, stem cell factor (SCF) and thrombopoietin (TPO). Targeted HSC transduction is e...

  19. Large Animal Models of Hematopoietic Stem Cell Gene Therapy

    OpenAIRE

    Trobridge, Grant D.; Kiem, Hans-Peter

    2010-01-01

    Large animal models have been instrumental in advancing hematopoietic stem cell (HSC) gene therapy. Here we review the advantages of large animal models, their contributions to the field of HSC gene therapy, and recent progress in this field. Several properties of human HSCs including their purification, their cell-cycle characteristics, their response to cytokines, and the proliferative demands put on them after transplantation are more similar in large animal models than in mice. Progress i...

  20. Autologous Bone Marrow Stem Cells combined with Allograft Cancellous Bone in Treatment of Nonunion

    Directory of Open Access Journals (Sweden)

    Le Thua Trung Hau

    2015-12-01

    Full Text Available Autologous cancellous bone graft is currently used as a gold standard method for treatment of bone nonunion. However, there is a limit to the amount of autologous cancellous bone that can be harvested and the donor site morbidity presents a major disadvantage to autologous bone grafting. Embedding viable cells within biological scaffolds appears to be extremely promising. The purpose of this study was to assess the outcome of autologous bone marrow stem cells combined with a cancellous bone allograft as compared to an autologous bone graft in the treatment of bone nonunion. Bone marrow aspiration concentrate (BMAC was previously produced from bone marrow aspirate via a density gradient centrifugation. Autologous cancellous bone was harvested in 9 patients and applied to the nonunion site. In 18 patients of the clinical trial group after the debridement, the bone gaps were filled with a composite of BMAC and allograft cancellous bone chips (BMAC-ACB. Bone consolidation was obtained in 88.9 %, and the mean interval between the cell transplantation and union was 4.6 +/- 1.5 months in the autograft group. Bone union rate was 94.4 % in group of composite BMAC-ACB implantation. The time to union in BMAC-ACB grafting group was 3.3 +/- 0.90 months, and led to faster healing when compared to the autograft. A mean concentration of autologous progenitor cells was found to be 2.43 +/- 1.03 (x106 CD34+ cells/ml, and a mean viability of CD34+ cells was 97.97 +/- 1.47 (%. This study shows that the implantation of BMAC has presented the efficacy for treatment of nonunion and may contribute an available alternative to autologous cancellous bone graft. But large clinical application of BM-MSCs requires a more appropriate and profound scientific investigations. [Biomed Res Ther 2015; 2(12.000: 409-417

  1. Measuring microRNA expression in mouse hematopoietic stem cells.

    Science.gov (United States)

    Hu, Wenhuo; Park, Christopher Y

    2014-01-01

    MicroRNAs (miRNAs) are important regulators of diverse biologic processes. In the hematopoietic system, miRNAs have been shown to regulate lineage fate decisions, mature immune effector cell function, apoptosis, and cell cycling, and a more limited number of miRNAs has been shown to regulate hematopoietic stem cell (HSC) self-renewal. Many of these miRNAs were initially identified as candidate regulators of HSC function by comparing miRNA expression in hematopoietic stem and progenitors cells (HSPCs) to their mature progeny. While the measurement of miRNA expression in rare cell populations such as HSCs poses practical challenges due to the low amount of RNA present, a number of techniques have been developed to measure miRNAs in small numbers of cells. Here, we describe our protocol for measuring miRNAs in purified mouse HSCs using a highly sensitive real-time quantitative PCR strategy that utilizes microfluidic array cards containing pre-spotted TaqMan probes that allows the detection of mature miRNAs in small reaction volumes. We also describe a simple data analysis method to evaluate miRNA expression profiling data using an open-source software package (HTqPCR) using mouse HSC miRNA profiling data generated in our lab. PMID:25062625

  2. Aging, Clonality, and Rejuvenation of Hematopoietic Stem Cells.

    Science.gov (United States)

    Akunuru, Shailaja; Geiger, Hartmut

    2016-08-01

    Aging is associated with reduced organ function and increased disease incidence. Hematopoietic stem cell (HSC) aging driven by both cell intrinsic and extrinsic factors is linked to impaired HSC self-renewal and regeneration, aging-associated immune remodeling, and increased leukemia incidence. Compromised DNA damage responses and the increased production of reactive oxygen species (ROS) have been previously causatively attributed to HSC aging. However, recent paradigm-shifting concepts, such as global epigenetic and cytoskeletal polarity shifts, cellular senescence, as well as the clonal selection of HSCs upon aging, provide new insights into HSC aging mechanisms. Rejuvenating agents that can reprogram the epigenetic status of aged HSCs or senolytic drugs that selectively deplete senescent cells provide promising translational avenues for attenuating hematopoietic aging and, potentially, alleviating aging-associated immune remodeling and myeloid malignancies. PMID:27380967

  3. Loss of quiescence and impaired function of CD34+/CD38low cells one year following autologous stem cell transplantation

    OpenAIRE

    Woolthuis, Carolien M.; Brouwers-Vos, Annet Z.; Huls, Gerwin; de Wolf, Joost Th. M.; Schuringa, Jan Jacob; Vellenga, Edo

    2013-01-01

    Patients who have undergone autologous stem cell transplantation are subsequently more susceptible to chemotherapy-induced bone marrow toxicity. In the present study, bone marrow primitive progenitor cells were examined one year after autologous stem cell transplantation and compared with normal bone marrow and mobilized peripheral blood stem cells. Post-transplantation bone marrow contained a significantly lower percentage of quiescent cells in the CD34+/CD38low fraction compared to normal b...

  4. Lentiviral hematopoietic stem cell gene therapy for X-linked severe combined immunodeficiency.

    Science.gov (United States)

    De Ravin, Suk See; Wu, Xiaolin; Moir, Susan; Anaya-O'Brien, Sandra; Kwatemaa, Nana; Littel, Patricia; Theobald, Narda; Choi, Uimook; Su, Ling; Marquesen, Martha; Hilligoss, Dianne; Lee, Janet; Buckner, Clarissa M; Zarember, Kol A; O'Connor, Geraldine; McVicar, Daniel; Kuhns, Douglas; Throm, Robert E; Zhou, Sheng; Notarangelo, Luigi D; Hanson, I Celine; Cowan, Mort J; Kang, Elizabeth; Hadigan, Coleen; Meagher, Michael; Gray, John T; Sorrentino, Brian P; Malech, Harry L

    2016-04-20

    X-linked severe combined immunodeficiency (SCID-X1) is a profound deficiency of T, B, and natural killer (NK) cell immunity caused by mutations inIL2RGencoding the common chain (γc) of several interleukin receptors. Gamma-retroviral (γRV) gene therapy of SCID-X1 infants without conditioning restores T cell immunity without B or NK cell correction, but similar treatment fails in older SCID-X1 children. We used a lentiviral gene therapy approach to treat five SCID-X1 patients with persistent immune dysfunction despite haploidentical hematopoietic stem cell (HSC) transplant in infancy. Follow-up data from two older patients demonstrate that lentiviral vector γc transduced autologous HSC gene therapy after nonmyeloablative busulfan conditioning achieves selective expansion of gene-marked T, NK, and B cells, which is associated with sustained restoration of humoral responses to immunization and clinical improvement at 2 to 3 years after treatment. Similar gene marking levels have been achieved in three younger patients, albeit with only 6 to 9 months of follow-up. Lentiviral gene therapy with reduced-intensity conditioning appears safe and can restore humoral immune function to posthaploidentical transplant older patients with SCID-X1. PMID:27099176

  5. Differentiation within autologous fibrin scaffolds of porcine dermal cells with the mesenchymal stem cell phenotype

    Energy Technology Data Exchange (ETDEWEB)

    Puente, Pilar de la, E-mail: pilardelapuentegarcia@gmail.com [Tissue Bank, San Francisco Clinic Foundation, Av./Facultad 51, 5°, 24004 León (Spain); Ludeña, Dolores [Pathology Service, University Hospital of Salamanca, P/San Vicente 58-182, 37007 Salamanca (Spain); López, Marta; Ramos, Jennifer; Iglesias, Javier [Tissue Bank, San Francisco Clinic Foundation, Av./Facultad 51, 5°, 24004 León (Spain)

    2013-02-01

    Porcine mesenchymal stem cells (pMSCs) are an attractive source of cells for tissue engineering because their properties are similar to those of human stem cells. pMSCs can be found in different tissues but their dermal origin has not been studied in depth. Additionally, MSCs differentiation in monolayer cultures requires subcultured cells, and these cells are at risk of dedifferentiation when implanting them into living tissue. Following this, we attempted to characterize the MSCs phenotype of porcine dermal cells and to evaluate their cellular proliferation and differentiation in autologous fibrin scaffolds (AFSs). Dermal biopsies and blood samples were obtained from 12 pigs. Dermal cells were characterized by flow cytometry. Frozen autologous plasma was used to prepare AFSs. pMSC differentiation was studied in standard structures (monolayers and pellets) and in AFSs. The pMSCs expressed the CD90 and CD29 markers of the mesenchymal lineage. AFSs afforded adipogenic, osteogenic and chondrogenic differentiation. The porcine dermis can be proposed to be a good source of MSCs with adequate proliferative capacity and a suitable expression of markers. The pMSCs also showed optimal proliferation and differentiation in AFSs, such that these might serve as a promising autologous and implantable material for use in tissue engineering. -- Highlights: ► Low fibrinogen concentration provides a suitable matrix for cell migration and differentiation. ► Autologous fibrin scaffolds is a promising technique in tissue engineering. ► Dermal cells are an easily accessible mesenchymal stem cell source. ► Fibrin scaffolds afforded adipogenic, osteogenic and chondrogenic differentiation.

  6. Differentiation within autologous fibrin scaffolds of porcine dermal cells with the mesenchymal stem cell phenotype

    International Nuclear Information System (INIS)

    Porcine mesenchymal stem cells (pMSCs) are an attractive source of cells for tissue engineering because their properties are similar to those of human stem cells. pMSCs can be found in different tissues but their dermal origin has not been studied in depth. Additionally, MSCs differentiation in monolayer cultures requires subcultured cells, and these cells are at risk of dedifferentiation when implanting them into living tissue. Following this, we attempted to characterize the MSCs phenotype of porcine dermal cells and to evaluate their cellular proliferation and differentiation in autologous fibrin scaffolds (AFSs). Dermal biopsies and blood samples were obtained from 12 pigs. Dermal cells were characterized by flow cytometry. Frozen autologous plasma was used to prepare AFSs. pMSC differentiation was studied in standard structures (monolayers and pellets) and in AFSs. The pMSCs expressed the CD90 and CD29 markers of the mesenchymal lineage. AFSs afforded adipogenic, osteogenic and chondrogenic differentiation. The porcine dermis can be proposed to be a good source of MSCs with adequate proliferative capacity and a suitable expression of markers. The pMSCs also showed optimal proliferation and differentiation in AFSs, such that these might serve as a promising autologous and implantable material for use in tissue engineering. -- Highlights: ► Low fibrinogen concentration provides a suitable matrix for cell migration and differentiation. ► Autologous fibrin scaffolds is a promising technique in tissue engineering. ► Dermal cells are an easily accessible mesenchymal stem cell source. ► Fibrin scaffolds afforded adipogenic, osteogenic and chondrogenic differentiation.

  7. Stepwise development of hematopoietic stem cells from embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Kenji Matsumoto

    Full Text Available The cellular ontogeny of hematopoietic stem cells (HSCs remains poorly understood because their isolation from and their identification in early developing small embryos are difficult. We attempted to dissect early developmental stages of HSCs using an in vitro mouse embryonic stem cell (ESC differentiation system combined with inducible HOXB4 expression. Here we report the identification of pre-HSCs and an embryonic type of HSCs (embryonic HSCs as intermediate cells between ESCs and HSCs. Both pre-HSCs and embryonic HSCs were isolated by their c-Kit(+CD41(+CD45(- phenotype. Pre-HSCs did not engraft in irradiated adult mice. After co-culture with OP9 stromal cells and conditional expression of HOXB4, pre-HSCs gave rise to embryonic HSCs capable of engraftment and long-term reconstitution in irradiated adult mice. Blast colony assays revealed that most hemangioblast activity was detected apart from the pre-HSC population, implying the early divergence of pre-HSCs from hemangioblasts. Gene expression profiling suggests that a particular set of transcripts closely associated with adult HSCs is involved in the transition of pre-HSC to embryonic HSCs. We propose an HSC developmental model in which pre-HSCs and embryonic HSCs sequentially give rise to adult types of HSCs in a stepwise manner.

  8. HOXB4 can enhance the differentiation of embryonic stem cells by modulating the hematopoietic niche

    DEFF Research Database (Denmark)

    Jackson, Melany; Axton, Richard A; Taylor, A Helen; Wilson, Julie A; Gordon-Keylock, Sabrina A M; Kokkaliaris, Konstantinos D; Brickman, Joshua M; Schulz, Herbert; Hummel, Oliver; Hubner, Norbert; Forrester, Lesley M

    2012-01-01

    Hematopoietic differentiation of embryonic stem cells (ESCs) in vitro has been used as a model to study early hematopoietic development, and it is well documented that hematopoietic differentiation can be enhanced by overexpression of HOXB4. HOXB4 is expressed in hematopoietic progenitor cells...... ESCs. To test our hypothesis, we developed a conditionally activated HOXB4 expression system using the mutant estrogen receptor (ER(T2)) and showed that a pulse of HOXB4 prior to HPC emergence in differentiating ESCs led to an increase in hematopoietic differentiation. Expression profiling revealed an...

  9. Mitigation of radiation induced hematopoietic injury via regulation of Nrf-2 and increasing hematopoietic stem cells

    International Nuclear Information System (INIS)

    Therapeutic doses of ionizing radiation (IR) that can be delivered to tumors are restricted due to radiation induced damage to surrounding normal tissues thereby limiting the effectiveness of radiotherapy. Strategies to develop agents that selectively protect normal cells yielded limited success in the past. There is pressing need to develop safe, syndrome specific and effective radiation countermeasures to prevent or mitigate the harmful consequences of radiation exposure. Survival of bone marrow stem cells (HSCs) play a key role in protecting against IR induced hematopoietic injury. Many studies have shown manipulation of HSC frequency and/or survival as principal mechanism of radioprotection. It is known that, Nrf-2 plays crucial role in HSC survival and maintenance under oxidative stress conditions. In the present study, we have investigated the radioprotective ability of a flavonoid baicalein (5,6,7-trihydroxyflavone), extracted from the root of Scutellaria baicalensis Georgi, a medicinal plant traditionally used in Oriental medicine. There are numerous reports showing anti-inflammatory, anti-apoptotic, anti-oxidant, anti-cancer, anti-microbial, anti-mutagenic and neuroprotective properties of baicalein. Based on these reports, we have investigated the ability of baicalein to protect against radiation induced hematopoietic injury. Baicalein administration to mice protected against WBI induced mortality. Interestingly, the stem cell frequency increased in bone marrow cells obtained from baicalein administered mice as compared to vehicle treated mice. Baicalein treatment led to increased phospho-Nrf-2 levels in lineage negative BM-MNC. Administration of mice with Nrf-2 inhibitor prior to baicalein treatment led to significant abrogation of radioprotective ability of baicalein. This result suggests that, Nrf-2 may be playing a key role in baicalein mediated radioprotection. Here, we have shown that baicalein administration augments stem cell frequency, induces

  10. Human T-Cell Clones from Autoimmune Thyroid Glands: Specific Recognition of Autologous Thyroid Cells

    Science.gov (United States)

    Londei, Marco; Bottazzo, G. Franco; Feldmann, Marc

    1985-04-01

    The thyroid glands of patients with autoimmune diseases such as Graves' disease and certain forms of goiter contain infiltrating activated T lymphocytes and, unlike cells of normal glands, the epithelial follicular cells strongly express histocompatability antigens of the HLA-DR type. In a study of such autoimmune disorders, the infiltrating T cells from the thyroid glands of two patients with Graves' disease were cloned in mitogen-free interleukin-2 (T-cell growth factor). The clones were expanded and their specificity was tested. Three types of clones were found. One group, of T4 phenotype, specifically recognized autologous thyroid cells. Another, also of T4 phenotype, recognized autologous thyroid or blood cells and thus responded positively in the autologous mixed lymphocyte reaction. Other clones derived from cells that were activated in vivo were of no known specificity. These clones provide a model of a human autoimmune disease and their analysis should clarify mechanisms of pathogenesis and provide clues to abrogating these undesirable immune responses.

  11. Quality of life before autologous stem cells transplantation as prognostic factor in patients with malignant lymphomas

    Directory of Open Access Journals (Sweden)

    Yu. L. Shevchenko

    2014-01-01

    Full Text Available Currently high-doses chemotherapy (HD-PCT + autologous hematopoietic stem cells transplantation (auto-HSCT is the treatment ofchoice in patients with recurrent and progressive lymphomas. Most of quality of life (QoL studies in lymphomas patients received HSCT limited on parameters dynamics assessment in the early and late post-transplant period. Aim of this study was to evaluate the QoL parameters and their prognostic significance in lymphoma patients before transplantation. 124 patients with lymphomas (non-Hodgkin lymphomas – 45 patients, Hodgkin's lymphoma – 79 patients who received HD-PCT + auto-HSCT were included in the study: men – 42.7 % (n = 53, women – 57.3 % (n = 71, median age – 34 years (19–65 years. Patients’ heterogeneity before transplantation regarding quality of life has been revealed. Almost 1/3 of patients showed a significant reduction in the integral index of QoL. Insignificant differences between patients with chemosensitivity and chemoresistant lymphomas regarding QoL before HD-PCT + auto-HSCT were shown. We also analyzed the outcomes of studied patients received HD-PCT + auto-HSCT. With a median follow-up of 18 months, overall survival after transplantation was 72 % (95 % CI 56–84; event-free survival – 64 % (95 % CI 53,3–73,2.Overall and event-free survivals were significantly higher in patients with chemosensitive lymphoma compared with chemoresistance tumor. Differences in the survival rates between patients with no or negligible decrease of QoL integral index and with significant reduction of it also were found. Revealed differences in overall and event-free survival between the groups allowed the first group considered as patients with a favorable prognosis, and the second group – as patients with poor prognosis regarding the transplantation outcome.

  12. Quality of life before autologous stem cells transplantation as prognostic factor in patients with malignant lymphomas

    Directory of Open Access Journals (Sweden)

    Yu. L. Shevchenko

    2014-07-01

    Full Text Available Currently high-doses chemotherapy (HD-PCT + autologous hematopoietic stem cells transplantation (auto-HSCT is the treatment ofchoice in patients with recurrent and progressive lymphomas. Most of quality of life (QoL studies in lymphomas patients received HSCT limited on parameters dynamics assessment in the early and late post-transplant period. Aim of this study was to evaluate the QoL parameters and their prognostic significance in lymphoma patients before transplantation. 124 patients with lymphomas (non-Hodgkin lymphomas – 45 patients, Hodgkin's lymphoma – 79 patients who received HD-PCT + auto-HSCT were included in the study: men – 42.7 % (n = 53, women – 57.3 % (n = 71, median age – 34 years (19–65 years. Patients’ heterogeneity before transplantation regarding quality of life has been revealed. Almost 1/3 of patients showed a significant reduction in the integral index of QoL. Insignificant differences between patients with chemosensitivity and chemoresistant lymphomas regarding QoL before HD-PCT + auto-HSCT were shown. We also analyzed the outcomes of studied patients received HD-PCT + auto-HSCT. With a median follow-up of 18 months, overall survival after transplantation was 72 % (95 % CI 56–84; event-free survival – 64 % (95 % CI 53,3–73,2.Overall and event-free survivals were significantly higher in patients with chemosensitive lymphoma compared with chemoresistance tumor. Differences in the survival rates between patients with no or negligible decrease of QoL integral index and with significant reduction of it also were found. Revealed differences in overall and event-free survival between the groups allowed the first group considered as patients with a favorable prognosis, and the second group – as patients with poor prognosis regarding the transplantation outcome.

  13. 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.

  14. Lnk deficiency partially mitigates hematopoietic stem cell aging

    OpenAIRE

    Bersenev, Alexey; Rozenova, Krasimira; Balcerek, Joanna; JIANG, JING; Wu, Chao; Tong, Wei

    2012-01-01

    Upon aging, the number of hematopoietic stem cells (HSCs) in the bone marrow increases while their repopulation potential declines. Moreover, aged HSCs exhibit lineage bias in reconstitution experiments with an inclination towards myeloid at the expense of lymphoid potential. The adaptor protein Lnk is an important negative regulator of HSC homeostasis, as Lnk deficiency is associated with a 10-fold increase in HSC numbers in young mice. However, the age-related increase in functional HSC num...

  15. Massage for Children Undergoing Hematopoietic Cell Transplantation: A Qualitative Report

    OpenAIRE

    Ackerman, Sara L.; E. Anne Lown; Dvorak, Christopher C.; Dunn, Elizabeth A.; Abrams, Donald I; Horn, Biljana N.; Marcia Degelman; Cowan, Morton J.; Mehling, Wolf E.

    2012-01-01

    Background. No in-depth qualitative research exists about the effects of therapeutic massage with children hospitalized to undergo hematopoietic cell transplantation (HCT). The objective of this study is to describe parent caregivers' experience of the effects of massage/acupressure for their children undergoing HCT. Methods. We conducted a qualitative analysis of open-ended interviews with 15 parents of children in the intervention arm of a massage/acupressure trial. Children received both p...

  16. Bone Marrow Vascular Niche: Home for Hematopoietic Stem Cells

    OpenAIRE

    Ningning He; Lu Zhang; Jian Cui; Zongjin Li

    2014-01-01

    Though discovered later than osteoblastic niche, vascular niche has been regarded as an alternative indispensable niche operating regulation on hematopoietic stem cells (HSCs). As significant progresses gained on this type niche, it is gradually clear that the main work of vascular niche is undertaking to support hematopoiesis. However, compared to what have been defined in the mechanisms through which the osteoblastic niche regulates hematopoiesis, we know less in vascular niche. In this rev...

  17. NON-TRANSFERRIN-BOUND IRON IN HEMATOPOIETIC STEM CELL TRANSPLANTATION

    OpenAIRE

    Sahlstedt, Leila

    2015-01-01

    Hematopoietic stem cell transplantation (HSCT) is an intensive treatment often complicated by organ injuries. Non-transferrin-bound iron (NTBI), as an inducer of free oxygen radicals, is a potential factor in the pathogenesis of these complications. We studied the appearance and timing of NTBI in transplant patients and the possibility to prevent the occurrence of NTBI by binding it with apotransferrin administration. We showed that NTBI appears regularly during the peritransplantation period...

  18. Regulation of hematopoietic stem cells by their mature progeny

    OpenAIRE

    de Graaf, Carolyn A.; Kauppi, Maria; Baldwin, Tracey; D. Hyland, Craig; Metcalf, Donald; Willson, Tracy A.; Carpinelli, Marina R.; Smyth, Gordon K; Alexander, Warren S.; Hilton, Douglas J.

    2010-01-01

    Thrombopoietin (TPO), acting through its receptor Mpl, has two major physiological roles: ensuring production of sufficient platelets via stimulation of megakaryocyte production and maintaining hematopoietic stem cell (HSC) quiescence. Mpl also controls circulating TPO concentration via receptor-mediated internalization and degradation. Here, we demonstrate that the megakaryocytosis and increased platelet mass in mice with mutations in the Myb or p300 genes causes reduced circulating TPO conc...

  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. PMID:26012570

  20. Are hematopoietic stem cells involved in hepatocarcinogenesis?

    OpenAIRE

    Facciorusso, Antonio; Antonino, Matteo; Del Prete, Valentina; Neve, Viviana; Scavo, Maria Principia; Barone, Michele

    2014-01-01

    The liver has three cell lineages able to proliferate after a hepatic injury: the mature hepatocyte, the ductular “bipolar” progenitor cell termed “oval cell” and the putative periductular stem cell. Hepatocytes can only produce other hepatocytes whereas ductular progenitor cells are considerate bipolar since they can give rise to biliary cells or hepatocytes. Periductular stem cells are rare in the liver, have a very long proliferation potential and may be multipotent, being this aspect stil...

  1. Autologous cell therapy as a new approach to treatment of radiation-induced bone marrow aplasia: preliminary study in a baboon model

    Energy Technology Data Exchange (ETDEWEB)

    Herodin, F.; Drouet, M. [Radiohematology Unit, Centre de Recherches du Service de Sante des Armees, La Tronche CEDEX (France)

    2002-07-01

    The sparing of viable hematopoietic stem and progenitor cells located in underexposed bone marrow territories associated with the relative radioresistance of certain stem cell populations is the rationale for autologous cell therapy consisting of ex vivo expansion of residual cells after collection postirradiation. The feasibility of this treatment mainly depends on time constraints and hematopoietic cell threshold. We showed in this study that in the absence of early-acting mobilizing agent administration, subliminar amounts of CD34{sup +} cells can be collected (1 x 10{sup 6} CD34{sup +} cells/100 mL bone marrow or for 1 L apheresis) from 6-Gy {gamma} globally irradiated baboons. Residual CD34{sup +} cells were successfully expanded in serum-free medium in the presence of antiapoptotic cytokine combination (stem cell factor + FLT-3 ligand + thrombopoietin + interleukin 3, 50 ng/mL each, i.e., 4F): K{sub CD34{sup +}} = x2.8 and x13.7 (n=2). Moreover, we demonstrated the short-term neutrophil engraftment potential of a low-size mixed expanded graft (1.5 x 10{sup 6} final CD34{sup +}cells/kg) issued from the coculture of unirradiated (20%) and 2.5-Gy in vitro irradiated (80%) CD34{sup +} cells on an allogeneic stromal cell layer in the presence of 4F. Further preclinical research needs to be performed to clearly establish this therapeutic approach that could be optimized by the early administration of antiapoptotic cytokines. (author)

  2. Use of the quality management system "JACIE" and outcome after hematopoietic stem cell transplantation.

    Science.gov (United States)

    Gratwohl, Alois; Brand, Ronald; McGrath, Eoin; van Biezen, Anja; Sureda, Anna; Ljungman, Per; Baldomero, Helen; Chabannon, Christian; Apperley, Jane

    2014-05-01

    Competent authorities, healthcare payers and hospitals devote increasing resources to quality management systems but scientific analyses searching for an impact of these systems on clinical outcome remain scarce. Earlier data indicated a stepwise improvement in outcome after allogeneic hematopoietic stem cell transplantation with each phase of the accreditation process for the quality management system "JACIE". We therefore tested the hypothesis that working towards and achieving "JACIE" accreditation would accelerate improvement in outcome over calendar time. Overall mortality of the entire cohort of 107,904 patients who had a transplant (41,623 allogeneic, 39%; 66,281 autologous, 61%) between 1999 and 2006 decreased over the 14-year observation period by a factor of 0.63 per 10 years (hazard ratio: 0.63; 0.58-0.69). Considering "JACIE"-accredited centers as those with programs having achieved accreditation by November 2012, at the latest, this improvement was significantly faster in "JACIE"-accredited centers than in non-accredited centers (approximately 5.3% per year for 49,459 patients versus approximately 3.5% per year for 58,445 patients, respectively; hazard ratio: 0.83; 0.71-0.97). As a result, relapse-free survival (hazard ratio 0.85; 0.75-0.95) and overall survival (hazard ratio 0.86; 0.76-0.98) were significantly higher at 72 months for those patients transplanted in the 162 "JACIE"-accredited centers. No significant effects were observed after autologous transplants (hazard ratio 1.06; 0.99-1.13). Hence, working towards implementation of a quality management system triggers a dynamic process associated with a steeper reduction in mortality over the years and a significantly improved survival after allogeneic stem cell transplantation. Our data support the use of a quality management system for complex medical procedures. PMID:24488562

  3. Defining Molecular Phenotypes of Mesenchymal and hematopoietic Stem Cells derived from Peripheral blood of Acute Lymphocytic Leukemia patients for regenerative stem cell therapy

    Science.gov (United States)

    Potdar, PD; Subedi, RP

    2011-01-01

    Acute Lymphocytic Leukemia (ALL) is a clonal myeloid disorder affecting all age groups, characterized by accumulation of immature blast cells in bone marrow and in peripheral blood. Autologous Bone Marrow Transplantation is a present treatment for cure of ALL patients, which is very expensive, invasive process and may have possibility of transplantation of malignant stem cells to patients. In the present study, we hypothesized to isolate large number of normal Mesenchymal & Hematopoietic stem cells from peripheral blood of ALL patients, which will be further characterized for their normal phenotypes by using specific molecular stem cell markers. This is the first study, which defines the existing phenotypes of isolated MSCs and HSCs from peripheral blood of ALL patients. We have established three cell lines in which two were Mesenchymal stem cells designated as MSCALL and MSCnsALL and one was suspension cell line designated as HSCALL. The HSCALL cell line was developed from the lymphocyte like cells secreted by MSCALL cells. Our study also showed that MSCALL from peripheral blood of ALL patient secreted hematopoietic stem cells in vitro culture. We have characterized all three-cell lines by 14 specific stem cell molecular markers. It was found that both MSC cell lines expressed CD105, CD13, and CD73 with mixed expression of CD34 and CD45 at early passage whereas, HSCALL cell line expressed prominent feature of hematopoietic stem cells such as CD34 and CD45 with mild expression of CD105 and CD13. All three-cell lines expressed LIF, OCT4, NANOG, SOX2, IL6, and DAPK. These cells mildly expressed COX2 and did not express BCR-ABL. Overall it was shown that isolated MSCs and HSCs can be use as a model system to study the mechanism of leukemia at stem cell level and their use in stem cell regeneration therapy for Acute Lymphocytic Leukemia. PMID:24693170

  4. Defining Molecular Phenotypes of Mesenchymal and hematopoietic Stem Cells derived from Peripheral blood of Acute Lymphocytic Leukemia patients for regenerative stem cell therapy

    Directory of Open Access Journals (Sweden)

    Pravin D. Potdar

    2011-01-01

    Full Text Available Acute Lymphocytic Leukemia (ALL is a clonal myeloid disorder affecting all age groups, characterized by accumulation of immature blast cells in bone marrow and in peripheral blood. Autologous Bone Marrow Transplantation is a present treatment for cure of ALL patients, which is very expensive, invasive process and may have possibility of transplantation of malignant stem cells to patients. In the present study, we hypothesized to isolate large number of normal Mesenchymal & Hematopoietic stem cells from peripheral blood of ALL patients, which will be further characterized for their normal phenotypes by using specific molecular stem cell markers. This is the first study, which defines the existing phenotypes of isolated MSCs and HSCs from peripheral blood of ALL patients. We have established three cell lines in which two were Mesenchymal stem cells designated as MSCALL and MSCnsALL and one was suspension cell line designated as HSCALL. The HSCALL cell line was developed from the lymphocyte like cells secreted by MSCALL cells. Our study also showed that MSCALL from peripheral blood of ALL patient secreted hematopoietic stem cells in vitro culture. We have characterized all three-cell lines by 14 specific stem cell molecular markers. It was found that both MSC cell lines expressed CD105, CD13, and CD73 with mixed expression of CD34 and CD45 at early passage whereas, HSCALL cell line expressed prominent feature of hematopoietic stem cells such as CD34 and CD45 with mild expression of CD105 and CD13. All three-cell lines expressed LIF, OCT4, NANOG, SOX2, IL6, and DAPK. These cells mildly expressed COX2 and did not express BCR-ABL. Overall it was shown that isolated MSCs and HSCs can be use as a model system to study the mechanism of leukemia at stem cell level and their use in stem cell regeneration therapy for Acute Lymphocytic Leukemia.

  5. A comparison of HLA-identical sibling allogeneic versus autologous transplantation for diffuse large B cell lymphoma: a report from the CIBMTR.

    Science.gov (United States)

    Lazarus, Hillard M; Zhang, Mei-Jie; Carreras, Jeanette; Hayes-Lattin, Brandon M; Ataergin, Asli Selmin; Bitran, Jacob D; Bolwell, Brian J; Freytes, César O; Gale, Robert Peter; Goldstein, Steven C; Hale, Gregory A; Inwards, David J; Klumpp, Thomas R; Marks, David I; Maziarz, Richard T; McCarthy, Philip L; Pavlovsky, Santiago; Rizzo, J Douglas; Shea, Thomas C; Schouten, Harry C; Slavin, Shimon; Winter, Jane N; van Besien, Koen; Vose, Julie M; Hari, Parameswaran N

    2010-01-01

    We compared outcomes of 916 diffuse large B cell lymphoma (DLBCL) patients aged >or=18 years undergoing first autologous (n = 837) or myeloablative (MA) allogeneic hematopoietic cell transplant (HCT) (n = 79) between 1995 and 2003 reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). Median follow-up was 81 months for allogeneic HCT versus 60 months for autologous HCT. Allogeneic HCT recipients were more likely to have high-risk disease features including higher stage, more prior chemotherapy regimens, and resistant disease. Allogeneic HCT was associated with a higher 1 year treatment-related mortality (TRM) (relative risk [RR] 4.88, 95% confidence interval [CI], 3.21-7.40, P 50 years), lower performance score, chemoresistance, and earlier year of transplant. In a cohort of mainly high-risk DLBCL patients, upfront MA allogeneic HCT, although associated with increased early mortality, was associated with a similar risk of disease progression compared to lower risk patients receiving autologous HCT. PMID:20053330

  6. Cancer Immunotherapy Using Engineered Hematopoietic Stem Cells

    OpenAIRE

    Gschweng, Eric Hans

    2015-01-01

    Engineering the immune system against cancer ideally provides surgical precision against the antigen bearing target cell while avoiding the systemic, off-target toxicity of chemotherapy. Successful treatment of patients in the clinic has been achieved by the expression of anti-cancer T-cell receptors (TCR) and chimeric antigen receptors (CAR) in T cells followed by infusion of these cells into cancer patients. Unfortunately, while many patients initially respond showing anti-tumor efficacy, t...

  7. Bone Marrow GvHD after Allogeneic Hematopoietic Stem Cell Transplantation

    OpenAIRE

    Szyska, Martin; Na, Il-Kang

    2016-01-01

    The bone marrow is the origin of all hematopoietic lineages and an important homing site for memory cells of the adaptive immune system. It has recently emerged as a graft-versus-host disease (GvHD) target organ after allogeneic stem cell transplantation (alloHSCT), marked by depletion of both hematopoietic progenitors and niche-forming cells. Serious effects on the restoration of hematopoietic function and immunological memory are common, especially in patients after myeloablative conditioni...

  8. High-activity samarium-153-EDTMP therapy followed by autologous peripheral blood stem cell support in unresectable osteosarcoma

    International Nuclear Information System (INIS)

    Purpose: Despite highly efficacious chemotherapy, patients with osteosarcomas still have a poor prognosis if adequate surgical control cannot be obtained. These patients may benefit from therapy with radiolabeled phosphonates. Patients and Methods: Six patients (three male, three female; seven to 41 years) with unresectable primary osteosarcoma (n = 3) or unresectable recurrent sites of osteosarcomas (n = 3) were treated with high-activity of Sm-153-EDTMP (150 MBq/kg BW). In all patients autologous peripheral blood stem cells had been collected before Sm-153-EDTMP therapy. Results: No immediate adverse reactions were observed in the patients. In one patient bone pain increased during the first 48 hrs after therapy. Three patients received pain relief. Autologous peripheral blood stem cell reinfusion was performed on day +12 to +27 in all patients to overcome potentially irreversible damage to the hematopoietic stem cells. In three patient external radiotherapy of the primary tumor site was performed after Sm-153-EDTMP therapy and in two of them polychemotherapy was continued. Thirty-six months later one of these patients is still free of progression. Two further patients are still alive. However, they have developed new metastases. The three patients who had no accompanying external radiotherapy, all died of disease progression five to 20 months after therapy. Conclusion: These preliminary results show that high-dose Sm-153-EDTMP therapy is feasible and warrants further evaluation of efficacy. The combination with external radiation and polychemotherapy seems to be most promising. Although osteosarcoma is believed to be relatively radioresistant, the total focal dose achieved may delay local progression or even achieve permanent local tumor control in patients with surgically inaccessible primary or relapsing tumors. (orig.)

  9. 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. PMID:27220264

  10. Economics and Outcome After Hematopoietic Stem Cell Transplantation: A Retrospective Cohort Study

    Directory of Open Access Journals (Sweden)

    Alois Gratwohl

    2015-12-01

    Full Text Available Hematopoietic stem cell transplantation (HSCT is a lifesaving expensive medical procedure. Hence, more transplants are performed in more affluent countries. The impact of economic factors on patient outcome is less defined. We analyzed retrospectively a defined cohort of 102,549 patients treated with an allogeneic (N = 37,542; 37% or autologous (N = 65,007; 63% HSCT. They were transplanted by one of 404 HSCT centers in 25 European countries between 1999 and 2006. We searched for associations between center-specific microeconomic or country-specific macroeconomic factors and outcome. Center patient-volume and center program-duration were significantly and systematically associated with improved survival after allogeneic HSCT (HR 0·87; 0·84–0·91 per 10 patients; p < 0·0001; HR 0·90;0·85–0·90 per 10 years; p < 0·001 and autologous HSCT (HR 0·91;0·87–0·96 per 10 patients; p < 0·001; HR 0·93;0·87–0·99 per 10 years; p = 0·02. The product of Health Care Expenditures by Gross National Income/capita was significantly associated in multivariate analysis with all endpoints (R2 = 18%; for relapse free survival after allogeneic HSCT. Data indicate that country- and center-specific economic factors are associated with distinct, significant, systematic, and clinically relevant effects on survival after HSCT. They impact on center expertise in long-term disease and complication management. It is likely that these findings apply to other forms of complex treatments.

  11. Economics and Outcome After Hematopoietic Stem Cell Transplantation: A Retrospective Cohort Study.

    Science.gov (United States)

    Gratwohl, Alois; Sureda, Anna; Baldomero, Helen; Gratwohl, Michael; Dreger, Peter; Kröger, Nicolaus; Ljungman, Per; McGrath, Eoin; Mohty, Mohamad; Nagler, Arnon; Rambaldi, Alessandro; de Elvira, Carmen Ruiz; Snowden, John A; Passweg, Jakob; Apperley, Jane; Niederwieser, Dietger; Stijnen, Theo; Brand, Ronald

    2015-12-01

    Hematopoietic stem cell transplantation (HSCT) is a lifesaving expensive medical procedure. Hence, more transplants are performed in more affluent countries. The impact of economic factors on patient outcome is less defined. We analyzed retrospectively a defined cohort of 102,549 patients treated with an allogeneic (N = 37,542; 37%) or autologous (N = 65,007; 63%) HSCT. They were transplanted by one of 404 HSCT centers in 25 European countries between 1999 and 2006. We searched for associations between center-specific microeconomic or country-specific macroeconomic factors and outcome. Center patient-volume and center program-duration were significantly and systematically associated with improved survival after allogeneic HSCT (HR 0·87; 0·84-0·91 per 10 patients; p < 0·0001; HR 0·90;0·85-0·90 per 10 years; p < 0·001) and autologous HSCT (HR 0·91;0·87-0·96 per 10 patients; p < 0·001; HR 0·93;0·87-0·99 per 10 years; p = 0·02). The product of Health Care Expenditures by Gross National Income/capita was significantly associated in multivariate analysis with all endpoints (R(2) = 18%; for relapse free survival) after allogeneic HSCT. Data indicate that country- and center-specific economic factors are associated with distinct, significant, systematic, and clinically relevant effects on survival after HSCT. They impact on center expertise in long-term disease and complication management. It is likely that these findings apply to other forms of complex treatments. PMID:26844291

  12. Myeloablative Chemotherapy with Autologous Stem Cell Transplant for Desmoplastic Small Round Cell Tumor

    Directory of Open Access Journals (Sweden)

    Christopher J. Forlenza

    2015-01-01

    Full Text Available Desmoplastic small round cell tumor (DSRCT, a rare, aggressive neoplasm, has a poor prognosis. In this prospective study, we evaluated the role of myeloablative chemotherapy, followed by autologous stem cell transplant in improving survival in DSRCT. After high-dose induction chemotherapy and surgery, 19 patients with chemoresponsive DSRCT underwent autologous stem cell transplant. Myeloablative chemotherapy consisted of carboplatin (400–700 mg/m2/day for 3 days + thiotepa (300 mg/m2/day for 3 days ± topotecan (2 mg/m2/day for 5 days. All patients were engrafted and there was no treatment-related mortality. Seventeen patients received radiotherapy to sites of prior or residual disease at a median of 12 weeks after transplant. Five-year event-free and overall survival were 11 ± 7% and 16 ± 8%, respectively. Two patients survive disease-free 16 and 19 years after transplant (both in complete remission before transplant. 14 patients had progression and died of disease at a median of 18 months following autologous transplant. These data do not justify the use of myeloablative chemotherapy with carboplatin plus thiotepa in patients with DSRCT. Alternative therapies should be considered for this aggressive neoplasm.

  13. Hematopoietic Stem Cell Transplantation and History

    Directory of Open Access Journals (Sweden)

    Atila Tanyeli

    2014-02-01

    Full Text Available Attemps to employ marrow stem cell for therapeutic purpose began in 1940’s. Marrow transplantation might be of use not only in irradiation protection, but also with therapeutic aim to marrow aplasia, leukemia and other diseases. The use and defining tissue antigens in humans were crucial to the improving of transplantation. The administration of methotrexate for GVHD improved the long term survival. Conditioning regimens for myeloablation designed according to diseases. Cord blood and peripheral blood stem cells were used for transplantion after 1980’s. Cord blood and bone marrow stem cell banks established to find HLA matched donor.

  14. The Hematopoietic Stem Cell Therapy for Exploration of Space

    Science.gov (United States)

    Roach, Allana Nicole; Brezo, Jelena

    2002-01-01

    Astronauts experience severe/invasive disorders caused by space environments. These include hematological/cardiac abnormalities, bone and muscle losses, immunodeficiency, neurological disorders and cancer. While the cause of these symptoms are not yet fully delineated, one possible explanation could be the inhibition of hematopoietic stem cell (HSC) growth and hematopoiesis in space. HSCs differentiate into all types of blood cells, and growing evidence indicates that the HSCs also have the ability to transdifferentiate to various tissues, including muscle, skin, liver, neuronal cells and possibly bone. Therefore, a hypothesis was advanced in this laboratory that the hematopoietic stem cell-based therapy, herein called the hematopoietic stem cell therapy (HSCT), could mitigate some of the disorders described above. Due to the magnitude of this project our laboratory has subdivided it into 3 sections: a) HSCT for space anemia; b) HSCT for muscle and bone losses; and c) HSCT for immunodeficiency. Toward developing the HSCT protocol for space anemia, the HSC transplantation procedure was established using a mouse model of beta thalassemia. In addition, the NASA Rotating Wall Vessel (RWV) culture system was used to grow HSCs in space condition. To investigate the HSCT for muscle loss and bone loss, donor HSCs were genetically marked either by transfecting the beta-galactosidase-containing plasmid, pCMV.SPORT-beta-gal or by preparing from b-galactosidase transgenic mice. The transdifferentiation of HSCs to muscle is traced by the reporter gene expression in the hindlimb suspended mice with some positive outcome, as studied by the X-gal staining procedure. The possible structural contribution of HSCs against muscle loss is being investigated histochemically.

  15. Chronic phase CML patients possess T cells capable of recognising autologous tumour cells.

    Science.gov (United States)

    Müller, Ludmila; Pawelec, Graham

    2002-05-01

    Much circumstantial evidence points to the immunogenicity of chronic myloid leukemia (CML) cells, most impressively the well-established T cell-dependent GvL effect seen in bone marrow transplantation. However, only a small number of shared antigens expressed by CML cells have been identified as potential targets for T cell-mediated immune responses which might be exploited for immunotherapy. It may be that unique antigens expressed by individual tumours are more potent rejection antigens if the patient's own T cells could be encouraged to react against them. Work is reviewed here which documents that in vitro mixed cultures between autologous T cells and dendritic cells of chronic-phase CML patients can give rise to sensitised T cells capable of recognising the patient's tumour cells. Additionally, mixed autologous tumour cell/lymphocyte cultures, modified by the addition of cytokine cocktails, may also result in the generation of similarly sensitised T cells. These results could be exploited for adoptive immunotherapy, and possibly, after identification of the antigens recognised, also for active immunotherapy, i.e. including therapeutic vaccination. PMID:12148904

  16. Fatal CMV-Infection after Autologous Stem Cell Transplantation in Refractory Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    László Váróczy

    2012-01-01

    Full Text Available High-dose chemotherapy followed by autologous stem cell transplantation can be a rescue for patients with severe refractory systemic lupus erythematosus (SLE. However, the procedure might have fatal complications including infections and bleeding. We report on a young female patient with SLE whose disease started in her early childhood. After many years, severe renal, neurological, and bone marrow involvement developed that did not respond to conventional therapy. She was selected for autologous stem cell transplantation. A successful peripheral stem cell apheresis was performed in March 2006. The nonselected graft was reinfused in August 2006 after a conditioning chemotherapy containing high-dose cyclophosphamide and antithymocyte globulin. Engraftment was detected within 11 days. On the 38th posttransplant day, severe cytomegalovirus (CMV infection developed that included pneumonitis, hepatitis, and pancytopenia. The patient died in a week due to multiorgan failure. With her case, we want to call the attention to this rare, but lethal complication of the autologous transplantation.

  17. How do I perform hematopoietic progenitor cell selection?

    Science.gov (United States)

    Avecilla, Scott T; Goss, Cheryl; Bleau, Sharon; Tonon, Jo-Ann; Meagher, Richard C

    2016-05-01

    Graft-versus-host disease remains the most important source of morbidity and mortality associated with allogeneic stem cell transplantation. The implementation of hematopoietic progenitor cell (HPC) selection is employed by some stem cell processing facilities to mitigate this complication. Current cell selection methods include reducing the number of unwanted T cells (negative selection) and/or enriching CD34+ hematopoietic stem/progenitors (positive selection) using immunomagnetic beads subjected to magnetic fields within columns to separate out targeted cells. Unwanted side effects of cell selection as a result of T-cell reduction are primary graft failure, increased infection rates, delayed immune reconstitution, possible disease relapse, and posttransplant lymphoproliferative disease. The Miltenyi CliniMACS cell isolation system is the only device currently approved for clinical use by the Food and Drug Administration. It uses magnetic microbeads conjugated with a high-affinity anti-CD34 monoclonal antibody capable of binding to HPCs in marrow, peripheral blood, or umbilical cord blood products. The system results in significantly improved CD34+ cell recoveries (50%-100%) and consistent 3-log CD3+ T-cell reductions compared to previous generations of CD34+ cell selection procedures. In this article, the CliniMACS procedure is described in greater detail and the authors provide useful insight into modifications of the system. Successful implementation of cell selection procedures can have a significant positive clinical effect by greatly increasing the pool of donors for recipients requiring transplants. However, before a program implements cell selection techniques, it is important to consider the time and financial resources required to properly and safely perform these procedures. PMID:26919388

  18. Imaging of complications from hematopoietic stem cell transplant

    Directory of Open Access Journals (Sweden)

    Tarun Pandey

    2014-01-01

    Full Text Available Stem cell transplant has been the focus of clinical research for a long time given its potential to treat several incurable diseases like hematological malignancies, diabetes mellitus, and neuro-degenerative disorders like Parkinson disease. Hematopoietic stem cell transplantation (HSCT is the oldest and most widely used technique of stem cell transplant. HSCT has not only been used to treat hematological disorders including hematological malignancies, but has also been found useful in treamtent of genetic, immunological, and solid tumors like neuroblastoma, lymphoma, and germ cell tumors. In spite of the rapid advances in stem cell technology, success rate with this technique has not been universal and many complications have also been seen with this form of therapy. The key to a successful HSCT therapy lies in early diagnosis and effective management of complications associated with this treatment. Our article aims to review the role of imaging in diagnosis and management of stem cell transplant complications associated with HSCT.

  19. Imaging of complications from hematopoietic stem cell transplant.

    Science.gov (United States)

    Pandey, Tarun; Maximin, Suresh; Bhargava, Puneet

    2014-10-01

    Stem cell transplant has been the focus of clinical research for a long time given its potential to treat several incurable diseases like hematological malignancies, diabetes mellitus, and neuro-degenerative disorders like Parkinson disease. Hematopoietic stem cell transplantation (HSCT) is the oldest and most widely used technique of stem cell transplant. HSCT has not only been used to treat hematological disorders including hematological malignancies, but has also been found useful in treamtent of genetic, immunological, and solid tumors like neuroblastoma, lymphoma, and germ cell tumors. In spite of the rapid advances in stem cell technology, success rate with this technique has not been universal and many complications have also been seen with this form of therapy. The key to a successful HSCT therapy lies in early diagnosis and effective management of complications associated with this treatment. Our article aims to review the role of imaging in diagnosis and management of stem cell transplant complications associated with HSCT. PMID:25489126

  20. 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

  1. Research progresses in treating diabetic foot with autologous stem cell transplantation

    International Nuclear Information System (INIS)

    Because the distal arteries of lower extremities become narrowed or even occluded in diabetic foot, the clinical therapeutic results for diabetic foot have been unsatisfactory so far. Autologous stem cell transplantation that has emerged in recent years is a new, safe and effective therapy for diabetic foot, which achieves its excellent clinical success in restoring the blood supply of ischemic limb by way of therapeutic angiogenesis. Now autologous stem cell transplantation has become one of the hot points in medical research both at home and abroad, moreover, it has brought a new hope of cure to the patients with diabetic foot. (authors)

  2. Autologous Bone Marrow Stem Cell Infusion (AMBI therapy for Chronic Liver Diseases

    Directory of Open Access Journals (Sweden)

    Rajkumar JS

    2007-01-01

    Full Text Available Liver Cirrhosis is the end stage of chronic liver disease which may happen due to alcoholism, viral infections due to Hepatitis B, Hepatitis C viruses and is difficult to treat. Liver transplantation is the only available definitive treatment which is marred by lack of donors, post operative complications such as rejection and high cost. Autologous bone marrow stem cells have shown a lot of promise in earlier reported animal studies and clinical trials. We have in this study administered in 22 patients with chronic liver disease, autologous bone marrow stem cell whose results are presented herewith.

  3. The Mechanisms of Human Renal Epithelial Cell Modulation of Autologous Dendritic Cell Phenotype and Function.

    Directory of Open Access Journals (Sweden)

    Sandeep Sampangi

    Full Text Available Proximal tubule epithelial cells (PTEC of the kidney line the proximal tubule downstream of the glomerulus and play a major role in the re-absorption of small molecular weight proteins that may pass through the glomerular filtration process. In the perturbed disease state PTEC also contribute to the inflammatory disease process via both positive and negative mechanisms via the production of inflammatory cytokines which chemo-attract leukocytes and the subsequent down-modulation of these cells to prevent uncontrolled inflammatory responses. It is well established that dendritic cells are responsible for the initiation and direction of adaptive immune responses. Both resident and infiltrating dendritic cells are localised within the tubulointerstitium of the renal cortex, in close apposition to PTEC, in inflammatory disease states. We previously demonstrated that inflammatory PTEC are able to modulate autologous human dendritic cell phenotype and functional responses. Here we extend these findings to characterise the mechanisms of this PTEC immune-modulation using primary human PTEC and autologous monocyte-derived dendritic cells (MoDC as the model system. We demonstrate that PTEC express three inhibitory molecules: (i cell surface PD-L1 that induces MoDC expression of PD-L1; (ii intracellular IDO that maintains the expression of MoDC CD14, drives the expression of CD80, PD-L1 and IL-10 by MoDC and inhibits T cell stimulatory capacity; and (iii soluble HLA-G (sHLA-G that inhibits HLA-DR and induces IL-10 expression by MoDC. Collectively the results demonstrate that primary human PTEC are able to modulate autologous DC phenotype and function via multiple complex pathways. Further dissection of these pathways is essential to target therapeutic strategies in the treatment of inflammatory kidney disorders.

  4. Thrombopoietin Induces HOXA9 Nuclear Transport in Immature Hematopoietic Cells: Potential Mechanism by Which the Hormone Favorably Affects Hematopoietic Stem Cells

    OpenAIRE

    Kirito, Keita; Fox, Norma; Kaushansky, Kenneth

    2004-01-01

    Members of the homeobox family of transcription factors are major regulators of hematopoiesis. Overexpression of either HOXB4 or HOXA9 in primitive marrow cells enhances the expansion of hematopoietic stem cells (HSCs). However, little is known of how expression or function of these proteins is regulated during hematopoiesis under physiological conditions. In our previous studies we demonstrated that thrombopoietin (TPO) enhances levels of HOXB4 mRNA in primitive hematopoietic cells (K. Kirit...

  5. 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...... risk of skin 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...... highest for RTRs. Autologous HSCT recipients had no increased risk of skin cancer. CONCLUSIONS AND RELEVANCE: Allogeneic HSCT recipients have an increased risk of BCC, SCC, and MM. Total-body irradiation was a major determinant for BCC. Our findings indicate the relevance of dermatologic follow-up in HSCT...

  6. Time to Insurance Approval in Private and Public Payers Does Not Influence Survival in Patients Who Undergo Hematopoietic Cell Transplantation.

    Science.gov (United States)

    Bhatt, Vijaya Raj; Loberiza, Fausto R; Schmit-Pokorny, Kim; Lee, Stephanie J

    2016-06-01

    In the United States, insurance status has been implicated as a barrier to obtaining timely treatment. In this retrospective cohort study of 521 patients who underwent first hematopoietic cell transplantation (HCT), we investigated the association between timeliness of HCT and overall survival. Timeliness was operationally defined in the following 3 ways: (1) payer approval, from request for approval to actual payer approval; (2) transplantation speed, from payer approval to time of actual HCT; and (3) total time, from request for approval to HCT. Patients with private insurance had longer time to payer approval (P HCT (P HCT (P HCT in lymphoma (n = 278), and autologous HCT in multiple myeloma (n = 121). Additional studies to evaluate the effect of insurance timeliness on all patients for whom HCT is recommended, not just those who undergo HCT, should be conducted. PMID:26988742

  7. Repurposing Treprostinil for Enhancing Hematopoietic Progenitor Cell Transplantation.

    Science.gov (United States)

    Kazemi, Zahra; Bergmayr, Christian; Prchal-Murphy, Michaela; Javaheri, Tahereh; Themanns, Madeleine; Pham, Ha T T; Strohmaier, Wolfgang; Sexl, Veronika; Freissmuth, Michael; Zebedin-Brandl, Eva

    2016-06-01

    Activation of Gs-coupled receptors enhances engraftment of hematopoietic stem and progenitor cells (HSPCs). We tested the hypothesis that treprostinil, a prostacyclin analog approved for the treatment of pulmonary hypertension, can be repurposed to improve hematopoietic stem cell transplantation. Murine and human HSPCs were isolated from bone marrow and umbilical cord blood, respectively. Prostanoid receptor agonists and the combination thereof with forskolin were tested for their capacity to stimulate [(3)H]cAMP accumulation in HSPCs. Three independent approaches were employed to verify the ability of agonist-activated HSPCs to reconstitute the bone marrow in lethally irradiated recipient mice. The underlying mechanism was explored in cellular migration assays and by blocking C-X-C motif chemokine receptor 4 (CXCR4). Among several prostanoid agonists tested in combination with forskolin, treprostinil was most efficacious in raising intracellular cAMP levels in murine and human HPSCs. Injection of murine and human HSPCs, which had been pretreated with treprostinil and forskolin, enhanced survival of lethally irradiated recipient mice. Survival was further improved if recipient mice were subcutaneously administered treprostinil (0.15 mg kg(-1) 8 h(-1)) for 10 days. This regimen also reduced the number of HSPCs required to rescue lethally irradiated mice. Enhanced survival of recipient mice was causally related to treprostinil-enhanced CXCR4-dependent migration of HSPCs. Treprostinil stimulates the engraftment of human and murine hematopoietic stem cells without impairing their capacity for self-renewal. The investigated dose range corresponds to the dose approved for human use. Hence, these findings may be readily translated into a clinical application. PMID:26989084

  8. [Physiological regulation of hematopoietic stem cell and its molecular basis].

    Science.gov (United States)

    Dong, Fang; Hao, Sha; Cheng, Hui; Cheng, Tao

    2016-08-25

    As a classical type of tissue stem cells, hematopoietic stem cell (HSC) is the earliest discovered and has been widely applied in the clinic as a great successful example for stem cell therapy. Thus, HSC research represents a leading field in stem cell biology and regenerative medicine. Self-renewal, differentiation, quiescence, apoptosis and trafficking constitute major characteristics of functional HSCs. These characteristics also signify different dynamic states of HSC through physiological interactions with the microenvironment cues in vivo. This review covers our current knowledge on the physiological regulation of HSC and its underlying molecular mechanisms. It is our hope that this review will not only help our colleagues to understand how HSC is physiologically regulated but also serve as a good reference for the studies on stem cell and regenerative medicine in general. PMID:27546503

  9. The Hematopoietic Stem Cell Therapy for Exploration of Deep Space

    Science.gov (United States)

    Ohi, Seigo; Roach, Allana-Nicole; Fitzgerald, Wendy; Riley, Danny A.; Gonda, Steven R.

    2003-01-01

    It is hypothesized that the hematopoietic stem cell therapy (HSCT) might countermeasure various space-caused disorders so as to maintain astronauts' homeostasis. If this were achievable, the HSCT could promote human exploration of deep space. Using animal models of disorders (hindlimb suspension unloading system and beta-thalassemia), the HSCT was tested for muscle loss, immunodeficiency and space anemia. The results indicate feasibility of HSCT for these disorders. To facilitate the HSCT in space, growth of HSCs were optimized in the NASA Rotating Wall Vessel (RWV) culture systems, including Hydrodynamic Focusing Bioreactor (HFB).

  10. Complications of central venous catheter in patients transplanted with hematopoietic stem cells in a specialized service

    Directory of Open Access Journals (Sweden)

    Lidiane Miotto Barretta

    2016-01-01

    Full Text Available Abstract Objective: to identify the model, average length of stay on site and complications of central venous catheter in patients undergoing transplant of hematopoietic stem cells and verify the corresponding relationship between the variables: age, gender, medical diagnosis, type of transplant, implanted catheter and insertion site. Method: a retrospective and quantitative study with a sample of 188 patients transplanted records between 2007 and 2011. Results: the majority of patients used Hickman catheter with an average length of stay on site of 47.6 days. The complication fever/bacteremia was significant in young males with non-Hodgkin's lymphoma undergoing autologous transplant, which remained with the device for a long period in the subclavian vein. Conclusion: nurses should plan with their team the minimum waiting time, recommended between the catheter insertion and start of the conditioning regimen, as well as not to extend the length of time that catheter should be on site and undertake their continuing education, focusing on the prevention of complications.

  11. Complications of central venous catheter in patients transplanted with hematopoietic stem cells in a specialized service

    Science.gov (United States)

    Barretta, Lidiane Miotto; Beccaria, Lúcia Marinilza; Cesarino, Cláudia Bernardi; Pinto, Maria Helena

    2016-01-01

    Abstract Objective: to identify the model, average length of stay on site and complications of central venous catheter in patients undergoing transplant of hematopoietic stem cells and verify the corresponding relationship between the variables: age, gender, medical diagnosis, type of transplant, implanted catheter and insertion site. Method: a retrospective and quantitative study with a sample of 188 patients transplanted records between 2007 and 2011. Results: the majority of patients used Hickman catheter with an average length of stay on site of 47.6 days. The complication fever/bacteremia was significant in young males with non-Hodgkin's lymphoma undergoing autologous transplant, which remained with the device for a long period in the subclavian vein. Conclusion: nurses should plan with their team the minimum waiting time, recommended between the catheter insertion and start of the conditioning regimen, as well as not to extend the length of time that catheter should be on site and undertake their continuing education, focusing on the prevention of complications. PMID:27276021

  12. High-dose chemotherapy followed by autologous stem cell transplantation for metastatic rhabdomyosarcoma--a systematic review.

    Directory of Open Access Journals (Sweden)

    Frank Peinemann

    Full Text Available INTRODUCTION: Patients with metastatic rhabdomyosarcoma (RMS have a poor prognosis. The aim of this systematic review is to investigate whether high-dose chemotherapy (HDCT followed by autologous hematopoietic stem cell transplantation (HSCT in patients with metastatic RMS has additional benefit or harm compared to standard chemotherapy. METHODS: Systematic literature searches were performed in MEDLINE, EMBASE, and The Cochrane Library. All databases were searched from inception to February 2010. PubMed was searched in June 2010 for a last update. In addition to randomized and non-randomized controlled trials, case series and case reports were included to complement results from scant data. The primary outcome was overall survival. A meta-analysis was performed using the hazard ratio as primary effect measure, which was estimated from Cox proportional hazard models or from summary statistics of Kaplan Meier product-limit estimations. RESULTS: A total of 40 studies with 287 transplant patients with metastatic RMS (age range 0 to 32 years were included in the assessment. We identified 3 non-randomized controlled trials. The 3-year overall survival ranged from 22% to 53% in the transplant groups vs. 18% to 55% in the control groups. Meta-analysis on overall survival in controlled trials showed no difference between treatments. Result of meta-analysis of pooled individual survival data of case series and case reports, and results from uncontrolled studies with aggregate data were in the range of those from controlled data. The risk of bias was high in all studies due to methodological flaws. CONCLUSIONS: HDCT followed by autologous HSCT in patients with RMS remains an experimental treatment. At present, it does not appear justifiable to use this treatment except in appropriately designed controlled trials.

  13. Engineering antigen-specific T cells from genetically modified human hematopoietic stem cells in immunodeficient mice.

    Directory of Open Access Journals (Sweden)

    Scott G Kitchen

    Full Text Available There is a desperate need for effective therapies to fight chronic viral infections. The immune response is normally fastidious at controlling the majority of viral infections and a therapeutic strategy aimed at reestablishing immune control represents a potentially powerful approach towards treating persistent viral infections. We examined the potential of genetically programming human hematopoietic stem cells to generate mature CD8+ cytotoxic T lymphocytes that express a molecularly cloned, "transgenic" human anti-HIV T cell receptor (TCR. Anti-HIV TCR transduction of human hematopoietic stem cells directed the maturation of a large population of polyfunctional, HIV-specific CD8+ cells capable of recognizing and killing viral antigen-presenting cells. Thus, through this proof-of-concept we propose that genetic engineering of human hematopoietic stem cells will allow the tailoring of effector T cell responses to fight HIV infection or other diseases that are characterized by the loss of immune control.

  14. Autologous stem-cell transplantation in refractory autoimmune diseases after in vivo immunoablation and ex vivo depletion of mononuclear cells

    OpenAIRE

    Rosen, Oliver; Thiel, Andreas; Massenkeil, Gero; Hiepe, Falk; Häupl, Thomas; Radtke, Hartmut; Burmester, Gerd R.; Gromnica-Ihle, Erika; Radbruch, Andreas; Arnold, Renate

    2000-01-01

    Introduction: Patients with persistently active autoimmune diseases are considered to be candidates for autologous SCT. We performed a phase 1/2 study in a limited number of patients who were refractory to conventional immunosuppressive treatment. Following a period of uncontrolled disease activity for at least 6 months, autologous SCT was performed, after in vivo immunoablation and ex vivo depletion of mononuclear cells. Aims: To investigate feasibility, toxicity and efficacy of the treatmen...

  15. Effects of hematopoietic growth factors on purified bone marrow progenitor cells

    NARCIS (Netherlands)

    F.J. Bot (Freek)

    1992-01-01

    textabstractWe have used highly enriched hematopoietic progenitor cells and in-vitro culture to examine the following questions: 1. The effects of recombinant lL-3 and GM-CSF on proliferation and differentiation of enriched hematopoietic progenitor cells have not been clearly defined: - how do IL~3

  16. Analysis and manipulation of hematopoietic progenitor and stem cells from murine embryonic tissues

    NARCIS (Netherlands)

    A. Medvinsky (Alexander); S. Taoudi (Samir); S.C. Mendes (Sandra); E.A. Dzierzak (Elaine)

    2008-01-01

    textabstractHematopoietic development begins in several locations in the mammalian embryo: yolk sac, aorta-gonad-mesonephros region (AGM), and the chorio-allantoic placenta. Generation of the most potent cells, adult definitive hematopoietic stem cells (HSCs), occurs within the body of the mouse emb

  17. Estradiol increases hematopoietic stem and progenitor cells independent of its actions on bone

    NARCIS (Netherlands)

    Illing, Anett; Liu, Peng; Ostermay, Susanne; Schilling, Arndt; de Haan, Gerald; Krust, Andree; Amling, Michael; Chambon, Pierre; Schinke, Thorsten; Tuckermann, Jan P.

    2012-01-01

    Hematopoietic stem and progenitor cells reside in vascular and endosteal niches in the bone marrow. Factors affecting bone remodeling were reported to influence numbers and mobilization of hematopoietic stem cells. We therefore analyzed the effects of estradiol acting anabolic on bone integrity. Her

  18. Human thymic epithelial cells directly induce activation of autologous immature thymocytes.

    OpenAIRE

    Denning, S M; Kurtzberg, J; Le, P. T.; Tuck, D T; Singer, K H; Haynes, B. F.

    1988-01-01

    To study the role that epithelial cells of the thymic microenvironment play in promoting activation of immature CD7+, CD2+, CD4-, CD8- (double-negative) human thymocytes, we have isolated thymocyte subsets from normal postnatal thymus and have cocultured autologous double-negative thymocytes with pure populations of thymic epithelial (TE) cells. We report that TE cells directly activate double-negative thymocytes to proliferate and that TE cells enhance the ability of double-negative thymocyt...

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

    Directory of Open Access Journals (Sweden)

    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

  20. 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. PMID:26030046

  1. Exercise as an Adjuvant Therapy for Hematopoietic Stem Cell Mobilization

    Science.gov (United States)

    Emmons, Russell; Niemiro, Grace M.; De Lisio, Michael

    2016-01-01

    Hematopoietic stem cell transplant (HSCT) using mobilized peripheral blood hematopoietic stem cells (HSPCs) is the only curative strategy for many patients suffering from hematological malignancies. HSPC collection protocols rely on pharmacological agents to mobilize HSPCs to peripheral blood. Limitations including variable donor responses and long dosing protocols merit further investigations into adjuvant therapies to enhance the efficiency of HSPCs collection. Exercise, a safe and feasible intervention in patients undergoing HSCT, has been previously shown to robustly stimulate HSPC mobilization from the bone marrow. Exercise-induced HSPC mobilization is transient limiting its current clinical potential. Thus, a deeper investigation of the mechanisms responsible for exercise-induced HSPC mobilization and the factors responsible for removal of HSPCs from circulation following exercise is warranted. The present review will describe current research on exercise and HSPC mobilization, outline the potential mechanisms responsible for exercise-induced HSPC mobilization, and highlight potential sites for HSPC homing following exercise. We also outline current barriers to the implementation of exercise as an adjuvant therapy for HSPC mobilization and suggest potential strategies to overcome these barriers. PMID:27123008

  2. Induced autologous stem cell transplantation for treatment of rabbit renal interstitial fibrosis.

    Directory of Open Access Journals (Sweden)

    Guang-Ping Ruan

    Full Text Available INTRODUCTION: Renal interstitial fibrosis (RIF is a significant cause of end-stage renal failure. The goal of this study was to characterize the distribution of transplanted induced autologous stem cells in a rabbit model of renal interstitial fibrosis and evaluate its therapeutic efficacy for treatment of renal interstitial fibrosis. METHODS: A rabbit model of renal interstitial fibrosis was established. Autologous fibroblasts were cultured, induced and labeled with green fluorescent protein (GFP. These labeled stem cells were transplanted into the renal artery of model animals at 8 weeks. RESULTS: Eight weeks following transplantation of induced autologous stem cells, significant reductions (P < 0.05 were observed in serum creatinine (SCr (14.8 ± 1.9 mmol/L to 10.1 ± 2.1 mmol/L and blood urea nitrogen (BUN (119 ± 22 µmol/L to 97 ± 13 µmol/L, indicating improvement in renal function. CONCLUSIONS: We successfully established a rabbit model of renal interstitial fibrosis and demonstrated that transplantation of induced autologous stem cells can repair kidney damage within 8 weeks. The repair occurred by both inhibition of further development of renal interstitial fibrosis and partial reversal of pre-existing renal interstitial fibrosis. These beneficial effects lead to the development of normal tissue structure and improved renal function.

  3. Intrathecal application of autologous bone marrow cell preparations in parkinsonian syndromes

    DEFF Research Database (Denmark)

    Storch, Alexander; Csoti, Ilona; Eggert, Karla;

    2012-01-01

    A growing number of patients is treated with intrathecal application of autologous bone marrow cells (aBMCs), but clinical data are completely lacking in movement disorders. We provide first clinical data on efficacy and safety of this highly experimental treatment approach in parkinsonian...

  4. File list: DNS.Bld.20.AllAg.CD34_Hematopoietic_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Bld.20.AllAg.CD34_Hematopoietic_stem_cells hg19 DNase-seq Blood CD34 Hematopoietic stem... cells SRX201280 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.Bld.20.AllAg.CD34_Hematopoietic_stem_cells.bed ...

  5. File list: His.Bld.20.AllAg.CD34_Hematopoietic_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.20.AllAg.CD34_Hematopoietic_stem_cells hg19 Histone Blood CD34 Hematopoietic stem... cells SRX026654 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Bld.20.AllAg.CD34_Hematopoietic_stem_cells.bed ...

  6. File list: DNS.Bld.50.AllAg.CD34_Hematopoietic_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Bld.50.AllAg.CD34_Hematopoietic_stem_cells hg19 DNase-seq Blood CD34 Hematopoietic stem... cells SRX201280 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.Bld.50.AllAg.CD34_Hematopoietic_stem_cells.bed ...

  7. File list: His.Bld.05.AllAg.CD34_Hematopoietic_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.05.AllAg.CD34_Hematopoietic_stem_cells hg19 Histone Blood CD34 Hematopoietic stem... cells SRX026654 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Bld.05.AllAg.CD34_Hematopoietic_stem_cells.bed ...

  8. Plasmacytoid dendritic cells in allogeneic hematopoietic cell transplantation: benefit or burden?

    Science.gov (United States)

    Auletta, JJ; Devine, SM; Waller, EK

    2016-01-01

    Plasmacytoid dendritic cells (pDCs) bridge innate and adaptive immune responses and have important roles in hematopoietic engraftment, GvHD and graft-versus-leukemia responses following allogeneic hematopoietic cell transplantation (HCT). In addition, pDCs mediate antiviral immunity, particularly as they are the body’s primary cellular source of type I interferon. Given their pleiotropic roles, pDCs have emerged as cells that critically impact transplant outcomes, including overall survival. In this article, we will review the pre-clinical and clinical literature, supporting the crucial roles that pDCs assume as key immune effector cells during HCT. PMID:26642333

  9. Characterization of a human hematopoietic progenitor cell capable of forming blast cell containing colonies in vitro.

    OpenAIRE

    J. Brandt; Baird, N; Lu, L; Srour, E; R. HOFFMAN

    1988-01-01

    A hematopoietic cell (CFU-B1) capable of producing blast cell containing colonies in vitro was detected using a semisolid culture system. The CFU-B1 has the capacity for self-renewal and commitment to a number of hematopoietic lineages. Monoclonal antibody to the human progenitor cell antigen-1 (HPCA-1) and a monoclonal antibody against the major histocompatibility class II antigen (HLA-DR) were used with fluorescence activated cell sorting to phenotype the CFU-B1. The CFU-B1 was found to exp...

  10. Low antigenicity of hematopoietic progenitor cells derived from human ES cells

    Directory of Open Access Journals (Sweden)

    Eun-Mi Kim

    2010-02-01

    Full Text Available Eun-Mi Kim1, Nicholas Zavazava1,21Department of Internal Medicine, University of Iowa and Veterans Affairs Medical Center, Iowa City, Iowa, USA; 2Immunology Graduate Program, University of Iowa, Iowa City, Iowa, USAAbstract: Human embryonic stem (hES cells are essential for improved understanding of diseases and our ability to probe new therapies for use in humans. Currently, bone marrow cells and cord blood cells are used for transplantation into patients with hematopoietic malignancies, immunodeficiencies and in some cases for the treatment of autoimmune diseases. However, due to the high immunogenicity of these hematopoietic cells, toxic regimens of drugs are required for preconditioning and prevention of rejection. Here, we investigated the efficiency of deriving hematopoietic progenitor cells (HPCs from the hES cell line H13, after co-culturing with the murine stromal cell line OP9. We show that HPCs derived from the H13 ES cells poorly express major histocompatibility complex (MHC class I and no detectable class II antigens (HLA-DR. These characteristics make hES cell-derived hematopoietic cells (HPCs ideal candidates for transplantation across MHC barriers under minimal immunosuppression.Keywords: human embryonic stem cells, H13, hematopoiesis, OP9 stromal cells, immunogenicity

  11. Natural killer cells in non-hematopoietic malignancies.

    Science.gov (United States)

    Desbois, Mélanie; Rusakiewicz, Sylvie; Locher, Clara; Zitvogel, Laurence; Chaput, Nathalie

    2012-01-01

    Natural killer (NK) cells belong to the innate immune system and were initially described functionallywise by their spontaneous cytotoxic potential against transformed or virus-infected cells. A delicate balance between activating and inhibiting receptors regulates NK cell tolerance. A better understanding of tissue resident NK cells, of NK cell maturation stages and migration patterns has evolved allowing a thoughtful evaluation of their modus operandi. While evidence has been brought up for their relevance as gate keepers in some hematopoietic malignancies, the role of NK cells against progression and dissemination of solid tumors remains questionable. Hence, many studies pointed out the functional defects of the rare NK cell infiltrates found in tumor beds and the lack of efficacy of adoptively transferred NK cells in patients. However, several preclinical evidences suggest their anti-metastatic role in a variety of mouse tumor models. In the present review, we discuss NK cell functions according to their maturation stage and environmental milieu, the receptor/ligand interactions dictating tumor cell recognition and recapitulate translational studies aimed at deciphering their prognostic or predictive role against human solid malignancies. PMID:23269924

  12. 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.

  13. The CD85j+ NK cell subset potently controls HIV-1 replication in autologous dendritic cells.

    Directory of Open Access Journals (Sweden)

    Daniel Scott-Algara

    Full Text Available Natural killer (NK cells and dendritic cells (DC are thought to play critical roles in the first phases of HIV infection. In this study, we examined changes in the NK cell repertoire and functions occurring in response to early interaction with HIV-infected DC, using an autologous in vitro NK/DC coculture system. We show that NK cell interaction with HIV-1-infected autologous monocyte-derived DC (MDDC modulates NK receptor expression. In particular, expression of the CD85j receptor on NK cells was strongly down-regulated upon coculture with HIV-1-infected MDDC. We demonstrate that CD85j(+ NK cells exert potent control of HIV-1 replication in single-round and productively HIV-1-infected MDDC, whereas CD85j(- NK cells induce a modest and transient decrease of HIV-1 replication. HIV-1 suppression in MDCC by CD85j(+ NK cells required cell-to-cell contact and did not appear mediated by cytotoxicity or by soluble factors. HIV-1 inhibition was abolished when NK-MDDC interaction through the CD85j receptor was blocked with a recombinant CD85j molecule, whereas inhibition was only slightly counteracted by blocking HLA class I molecules, which are known CD85j ligands. After masking HLA class I molecules with specific antibodies, a fraction of HIV-1 infected MDDC was still strongly stained by a recombinant CD85j protein. These results suggest that CD85j(+ NK cell inhibition of HIV-1 replication in MDDC is mainly mediated by CD85j interaction with an unknown ligand (distinct from HLA class I molecules preferentially expressed on HIV-1-infected MDDC.

  14. A hematopoietic contribution to microhemorrhage formation during antiviral CD8 T cell-initiated blood-brain barrier disruption

    Directory of Open Access Journals (Sweden)

    Johnson Holly L

    2012-03-01

    Full Text Available Abstract Background The extent to which susceptibility to brain hemorrhage is derived from blood-derived factors or stromal tissue remains largely unknown. We have developed an inducible model of CD8 T cell-initiated blood-brain barrier (BBB disruption using a variation of the Theiler's murine encephalomyelitis virus (TMEV model of multiple sclerosis. This peptide-induced fatal syndrome (PIFS model results in severe central nervous system (CNS vascular permeability and death in the C57BL/6 mouse strain, but not in the 129 SvIm mouse strain, despite the two strains' having indistinguishable CD8 T-cell responses. Therefore, we hypothesize that hematopoietic factors contribute to susceptibility to brain hemorrhage, CNS vascular permeability and death following induction of PIFS. Methods PIFS was induced by intravenous injection of VP2121-130 peptide at 7 days post-TMEV infection. We then investigated brain inflammation, astrocyte activation, vascular permeability, functional deficit and microhemorrhage formation using T2*-weighted magnetic resonance imaging (MRI in C57BL/6 and 129 SvIm mice. To investigate the contribution of hematopoietic cells in this model, hemorrhage-resistant 129 SvIm mice were reconstituted with C57BL/6 or autologous 129 SvIm bone marrow. Gadolinium-enhanced, T1-weighted MRI was used to visualize the extent of CNS vascular permeability after bone marrow transfer. Results C57BL/6 and 129 SvIm mice had similar inflammation in the CNS during acute infection. After administration of VP2121-130 peptide, however, C57BL/6 mice had increased astrocyte activation, CNS vascular permeability, microhemorrhage formation and functional deficits compared to 129 SvIm mice. The 129 SvIm mice reconstituted with C57BL/6 but not autologous bone marrow had increased microhemorrhage formation as measured by T2*-weighted MRI, exhibited a profound increase in CNS vascular permeability as measured by three-dimensional volumetric analysis of

  15. The Hematopoietic Stem Cell Therapy for Exploration of Space

    Science.gov (United States)

    Ohi, S.

    Departments of Biochemistry &Molecular Biology, Genetics &Human Genetics, Pediatrics &Child Long-duration space missions require countermeasures against severe/invasive disorders in astronauts that are caused by space environments, such as hematological/cardiac abnormalities, bone/muscle losses, immunodeficiency, neurological disorders, and cancer. Some, if not all, of these disorders may be amenable to hematopoietic stem cell therapy and gene therapy. Growing evidence indicates that hematopoietic stem cells (HSCs) possess extraordinary plasticity to differentiate not only to all types of blood cells but also to various tissues, including bone, muscle, skin, liver and neuronal cells. Therefore, our working hypothesis is that the hematopoietic stem cell-based therapy, herein called as the hematopoietic stem cell therapy (HSCT), might provide countermeasure/prevention for hematological abnormalities, bone and muscle losses in space, thereby maintaining astronauts' homeostasis. Our expertise lies in recombinant adeno-associated virus (rAAV)-mediated gene therapy for the hemoglobinopathies, -thalassemia and sickle cell disease (Ohi S, Kim BC, J Pharm Sci 85: 274-281, 1996; Ohi S, et al. Grav Space Biol Bull 14: 43, 2000). As the requisite steps in this protocol, we established procedures for purification of HSCs from both mouse and human bone marrow in 1 G. Furthermore, we developed an easily harvestable, long-term liquid suspension culture system, which lasts more than one year, for growing/expanding HSCs without stromal cells. Human globin cDNAs/gene were efficiently expressed from the rAAVs in the mouse HSCs in culture. Additionally, the NASA Rotating Wall Vessel (RWV) culture system is being optimized for the HSC growth/expansion. Thus, using these technologies, the above hypothesis is being investigated by the ground-based experiments as follows: 1) -thalassemic mice (C57BL/6-Hbbth/Hbbth, Hbd-minor) are transplanted with normal isologous HSCs to correct the

  16. [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. PMID:26861102

  17. The Hematopoietic Stem Cell Therapy for Exploration of Deep Space

    Science.gov (United States)

    Ohi, Seigo; Roach, Allana-Nicole; Ramsahai, Shweta; Kim, Bak C.; Fitzgerald, Wendy; Riley, Danny A.; Gonda, Steven R.

    2004-02-01

    Astronauts experience severe/invasive disorders caused by space environments. These include hematological and cardiac abnormalities, bone and muscle losses, immunodeficiency, neurological disorders and cancer. Exploiting the extraordinary plasticity of hematopoietic stem cells (HSCs), which differentiate not only to all types of blood cells, but also to various tissues, including muscle, bone, skin, liver, and neuronal cells, we advanced a hypothesis that some of the space-caused disorders might be amenable to hematopoietic stem cell therapy (HSCT) so as to maintain astronauts' homeostasis. If this were achievable, the HSCT could promote human exploration of deep space. Using mouse models of human anemia (β-thalassemia) and spaceflight (hindlimb suspension unloading system), we have obtained feasibility results of HSCT for space anemia, muscle loss, and immunodeficiency. For example, the β-thalassemic mice were successfully transplanted with isologous HSCs, resulting in chimerism of hemoglobin species and alleviation of the hemoglobinopathy. In the case of HSCT for muscle loss, β-galactosidase-marked HSCs, which were prepared from β-galactosidase-transgenic mice, were detected by the X-gal wholemount staining procedure in the hindlimbs of unloaded mice following transplantation. Histochemical and physical analyses indicated structural contribution of HSCs to the muscle. To investigate HSCT for immunodeficiency, β-galactosidase-transformed Escherichia coli was used as the reporter bacteria, and infected to control and the hindlimb suspended mice. Results of the X-gal stained tissues indicated that the HSCT could help eliminate the E. coli infection. In an effort to facilitate the HSCT in space, growth of HSCs has been optimized in the NASA Rotating Wall Vessel (RWV) culture systems, including Hydrodynamic Focusing Bioreactor (HFB).

  18. A novel complex, RUNX1-MYEF2, represses hematopoietic genes in erythroid cells

    NARCIS (Netherlands)

    B. van Riel (Boet); T. Pakozdi (Tibor); R.W.W. Brouwer; R. Monteiro (Rui); E. Tuladhar (Era); V. Franke (Vedran); J.C. Bryne; R.J.J. Jorna (Ruud); E.J. Rijkers; W.F.J. van IJcken (Wilfred); C. Andrieu-Soler (Charlotte); J.A.A. Demmers (Jeroen); R. Patient; E. Soler (Eric); B. Lenhard (Boris); F.G. Grosveld (Frank)

    2012-01-01

    textabstractRUNX1 is known to be an essential transcription factor for generating hematopoietic stem cells (HSC), but much less is known about its role in the downstream process of hematopoietic differentiation. RUNX1 has been shown to be part of a large transcription factor complex, together with L

  19. Of lineage and legacy: The development of mammalian hematopoietic stem cells

    NARCIS (Netherlands)

    E.A. Dzierzak (Elaine); N.A. Speck (Nancy)

    2008-01-01

    textabstractThe hematopoietic system is one of the first complex tissues to develop in the mammalian conceptus. Of particular interest in the field of developmental hematopoiesis is the origin of adult bone marrow hematopoietic stem cells. Tracing their origin is complicated because blood is a mobil

  20. Contribution of Bone Marrow Hematopoietic Stem Cells to Adult Mouse Inner Ear: Mesenchymal Cells and Fibrocytes

    OpenAIRE

    Lang, Hainan; Ebihara, Yasuhiro; Schmiedt, Richard A.; Minamiguchi, Hitoshi; Zhou, Daohong; Smythe, Nancy; LIU, LIYA; Ogawa, Makio; Schulte, Bradley A.

    2006-01-01

    Bone marrow (BM)-derived stem cells have shown plasticity with a capacity to differentiate into a variety of specialized cells. To test the hypothesis that some cells in the inner ear are derived from BM, we transplanted either isolated whole BM cells or clonally expanded hematopoietic stem cells (HSCs) prepared from transgenic mice expressing enhanced green fluorescent protein (EGFP) into irradiated adult mice. Isolated GFP+ BM cells also were transplanted into conditioned newborn mice deriv...

  1. File list: ALL.Bld.10.AllAg.CD34_Hematopoietic_stem_cells [Chip-atlas[Archive

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    Lifescience Database Archive (English)

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  10. ESAM is a novel human hematopoietic stem cell marker associated with a subset of human leukemias.

    Science.gov (United States)

    Ishibashi, Tomohiko; Yokota, Takafumi; Tanaka, Hirokazu; Ichii, Michiko; Sudo, Takao; Satoh, Yusuke; Doi, Yukiko; Ueda, Tomoaki; Tanimura, Akira; Hamanaka, Yuri; Ezoe, Sachiko; Shibayama, Hirohiko; Oritani, Kenji; Kanakura, Yuzuru

    2016-04-01

    Reliable markers are essential to increase our understanding of the biological features of human hematopoietic stem cells and to facilitate the application of hematopoietic stem cells in the field of transplantation and regenerative medicine. We previously identified endothelial cell-selective adhesion molecule (ESAM) as a novel functional marker of hematopoietic stem cells in mice. Here, we found that ESAM can also be used to purify human hematopoietic stem cells from all the currently available sources (adult bone marrow, mobilized peripheral blood, and cord blood). Multipotent colony-forming units and long-term hematopoietic-reconstituting cells in immunodeficient mice were found exclusively in the ESAM(High) fraction of CD34(+)CD38(-) cells. The CD34(+)CD38(-) fraction of cord blood and collagenase-treated bone marrow contained cells exhibiting extremely high expression of ESAM; these cells are likely to be related to the endothelial lineage. Leukemia cell lines of erythroid and megakaryocyte origin, but not those of myeloid or lymphoid descent, were ESAM positive. However, high ESAM expression was observed in some primary acute myeloid leukemia cells. Furthermore, KG-1a myeloid leukemia cells switched from ESAM negative to ESAM positive with repeated leukemia reconstitution in vivo. Thus, ESAM is a useful marker for studying both human hematopoietic stem cells and leukemia cells. PMID:26774386

  11. Stem cell transplantation for neuroblastoma

    OpenAIRE

    Fish, JD; Grupp, SA

    2007-01-01

    High-risk neuroblastoma is a childhood malignancy with a poor prognosis. Gradual improvements in survival have correlated with therapeutic intensity, and the ability to harvest, process and store autologous hematopoietic stem cells has allowed for dose intensification beyond marrow tolerance. The use of high-dose chemotherapy with autologous hematopoietic stem cell rescue in consolidation has resulted in improvements in survival, although further advances are still needed. Newer approaches to...

  12. Effect of cotransplantation of hematopoietic stem cells and embryonic AGM stromal cells on hematopoietic reconstitution in mice after bone marrow transplantation

    International Nuclear Information System (INIS)

    Objective: To explore the effects of cotransplantation of hematopoietic stem cells and stromal cells derived from aorta-gonad-mesonephros (AGM) region on hematopoietic reconstitution in mice after bone marrow transplantation (BMT). Methods: The typical mice model of syngeneic BMT was established and the mice were randomly divided into 4 groups: the control group, the BMT group, the group of cotransplantation of HSC with AGM stromal cells (the cotransplantation group) and the ligustrazine group (the LT group). On days 3, 7, 10, 14, 21 and 28 after BMT, the peripheral blood cells and bone marrow mononuclear cells (BMMNC) were counted, and histology changes of bone marrow were detected. Results: The levels of peripheral WBC, RBC, platelet, and BMMNC in the contransplantation group were significantly higher than those in the single BMT group and the LT group (P<0.05). Conclusions: Cotransplantation with AGM stromal cells could significantly promote hematopoietic reconstruction in mice after BMT. (authors)

  13. Directed differentiation of definitive hemogenic endothelium and hematopoietic progenitors from human pluripotent stem cells.

    Science.gov (United States)

    Ditadi, Andrea; Sturgeon, Christopher M

    2016-05-15

    The generation of hematopoietic stem cells (HSCs) from human pluripotent stem cells (hPSCs) remains a major goal for regenerative medicine and disease modeling. However, hPSC differentiation cultures produce mostly hematopoietic progenitors belonging to the embryonic HSC-independent hematopoietic program, which may not be relevant or accurate for modeling normal and disease-state adult hematopoietic processes. Through a stage-specific directed differentiation approach, it is now possible to generate exclusively definitive hematopoietic progenitors from hPSCs showing characteristics of the more developmentally advanced fetal hematopoiesis. Here, we summarize recent efforts at generating hPSC-derived definitive hematopoiesis through embryoid body differentiation under defined conditions. Embryoid bodies are generated through enzymatic dissociation of hPSCs from matrigel-coated plasticware, followed by recombinant BMP4, driving mesoderm specification. Definitive hematopoiesis is specified by a GSK3β-inhibitor, followed by recombinant VEGF and supportive hematopoietic cytokines. The CD34+ cells obtained using this method are then suitable for hematopoietic assays for definitive hematopoietic potential. PMID:26439174

  14. Concise Review: Guidance in Developing Commercializable Autologous/Patient-Specific Cell Therapy Manufacturing

    OpenAIRE

    Eaker, Shannon; Armant, Myriam; Brandwein, Harvey; Burger, Scott; Campbell, Andrew; Carpenito, Carmine; Clarke, Dominic; Fong, Timothy; Karnieli, Ohad; Niss, Knut; van"t Hof, Wouter; Wagey, Ravenska

    2013-01-01

    In this technical review, members of the International Society for Cell Therapy (ISCT) provide guidance in developing commercializable autologous and patient-specific manufacturing strategies from the perspective of process development. Guidance is provided to help small academic or biotech researchers determine what questions can be addressed at the bench level in order to make their cell therapy products more feasible for commercial-scale production.

  15. Placenta as a source of hematopoietic stem cells

    OpenAIRE

    Dzierzak, Elaine; Robin, Catherine

    2010-01-01

    The placenta is a large, highly vascularised hematopoietic tissue that functions during the embryonic and foetal development of eutherian mammals. Although recognised as the interface tissue important in the exchange of oxygen, nutrients and waste products between the foetus and mother, the placenta has increasingly become a focus of research concerning the ontogeny of the blood system. Here, we describe recent data showing the intrinsic hematopoietic potential and appearance of hematopoietic...

  16. Placenta as a source of hematopoietic stem cells

    OpenAIRE

    Dzierzak, Elaine; Robin, Catherine

    2010-01-01

    The placenta is a large, highly vascularized hematopoietic tissue that functions during embryonic and foetal development of eutherian mammals. Although recognized as the interface tissue important in the exchange of oxygen, nutrients and waste products between the foetus and mother, the placenta has increasingly become a focus of research concerning the ontogeny of the blood system. Here, we describe recent data showing the intrinsic hematopoietic potential and appearance of hematopoietic cel...

  17. Single-Cell RNA-Sequencing Reveals a Continuous Spectrum of Differentiation in Hematopoietic Cells

    Directory of Open Access Journals (Sweden)

    Iain C. Macaulay

    2016-02-01

    Full Text Available The transcriptional programs that govern hematopoiesis have been investigated primarily by population-level analysis of hematopoietic stem and progenitor cells, which cannot reveal the continuous nature of the differentiation process. Here we applied single-cell RNA-sequencing to a population of hematopoietic cells in zebrafish as they undergo thrombocyte lineage commitment. By reconstructing their developmental chronology computationally, we were able to place each cell along a continuum from stem cell to mature cell, refining the traditional lineage tree. The progression of cells along this continuum is characterized by a highly coordinated transcriptional program, displaying simultaneous suppression of genes involved in cell proliferation and ribosomal biogenesis as the expression of lineage specific genes increases. Within this program, there is substantial heterogeneity in the expression of the key lineage regulators. Overall, the total number of genes expressed, as well as the total mRNA content of the cell, decreases as the cells undergo lineage commitment.

  18. Intra-arterial Autologous Bone Marrow Cell Transplantation in a Patient with Upper-extremity Critical Limb Ischemia

    International Nuclear Information System (INIS)

    Induction of therapeutic angiogenesis by autologous bone marrow mononuclear cell transplantation has been identified as a potential new option in patients with advanced lower-limb ischemia. There is little evidence of the benefit of intra-arterial cell application in upper-limb critical ischemia. We describe a patient with upper-extremity critical limb ischemia with digital gangrene resulting from hypothenar hammer syndrome successfully treated by intra-arterial autologous bone marrow mononuclear cell transplantation.

  19. Bone Marrow Vascular Niche: Home for Hematopoietic Stem Cells

    Directory of Open Access Journals (Sweden)

    Ningning He

    2014-01-01

    Full Text Available Though discovered later than osteoblastic niche, vascular niche has been regarded as an alternative indispensable niche operating regulation on hematopoietic stem cells (HSCs. As significant progresses gained on this type niche, it is gradually clear that the main work of vascular niche is undertaking to support hematopoiesis. However, compared to what have been defined in the mechanisms through which the osteoblastic niche regulates hematopoiesis, we know less in vascular niche. In this review, based on research data hitherto we will focus on component foundation and various functions of vascular niche that guarantee the normal hematopoiesis process within bone marrow microenvironments. And the possible pathways raised by various research results through which this environment undergoes its function will be discussed as well.

  20. Graft rejection after hematopoietic cell transplantation with nonmyeloablative conditioning

    DEFF Research Database (Denmark)

    Masmas, T.N.; Petersen, S.L.; Madsen, H.O.; Ryder, L.P.; Kornblit, B.; Svejgaard, A.; Andersen, P.; Dickmeiss, E.; Vindelov, L.L.

    2008-01-01

    Graft rejection after hematopoietic cell transplantation (HCT) with nonmyeloablative conditioning is a rare but serious clinical problem. Graft rejection and salvage therapy in eight patients in a retrospective analysis of 124 consecutive patients is reported. The patients were conditioned with low......-dose fludarabine and total body irradiation (TBI). The association of pretransplantation risk factors with rejection and the effect of chimerism and graft-versus-host disease on rejection were analyzed. Overall survival (OS) and progression free survival (PFS) were compared between patients with and without......, patients are at greater risk of dying from infections and progression/relapse of their malignancy. Retransplantation is feasible and well tolerated after HCT with nonmyeloablative conditioning and should be performed without delay in patients with imminent and manifest graft rejection Udgivelsesdato: 2008/7...

  1. Bullous pemphigoid after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Kato, Keisuke; Koike, Kazutoshi; Kobayashi, Chie; Iijima, Shigeruko; Hashimoto, Takashi; Tsuchida, Masahiro

    2015-06-01

    Bullous pemphigoid (BP) is an autoimmune skin disorder characterized by subepidermal blisters due to deposit of autoantibody against dermal basement membrane protein. It has been reported that BP can occur after allogeneic hematopoietic stem cell transplantation (HSCT). We describe a patient with BP having autoantibody against BP180 after unrelated-donor HSCT against T lymphoblastic leukemia. The patient was treated with steroid leading to complete resolution of BP, but T lymphoblastic leukemia progressed rapidly after steroid hormone treatment. Given that immunosuppressant may reduce graft-versus-tumor effect, immunomodulatory agents such as nicotinamide and tetracycline, erythromycin, and immunoglobulin may be appropriate as soon as typical blister lesions are seen after HSCT. PMID:26113316

  2. Iron Overload in Patients Undergoing Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Vinod Pullarkat

    2010-01-01

    Full Text Available Recipients of hematopoietic stem cell transplantation (HSCT frequently have iron overload resulting from chronic transfusion therapy for anemia. In some cases, for example, in patients with myelodysplastic syndromes and thalassemia, this can be further exacerbated by increased absorption of iron from the gut as a result of ineffective erythropoiesis. Accumulating evidence has established the negative impact of elevated pretransplantation serum ferritin, a surrogate marker of iron overload, on overall survival and nonrelapse mortality after HSCT. Complications of HSCT associated with iron overload include increased bacterial and fungal infections as well as sinusoidal obstruction syndrome and possibly other regimen-related toxicities. Based on current evidence, particular attention should be paid to prevention and management of iron overload in allogeneic HSCT candidates, especially in patients with thalassemia and myelodysplastic syndromes. The pathophysiology of iron overload in the HSCT patient and optimum strategies to deal with iron overload during and after HSCT require further study.

  3. 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

    2016-01-01

    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 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. PMID:26372459

  4. 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.

  5. Analysis of the motivation for hematopoietic stem cell donation.

    Science.gov (United States)

    Aurelio, M T; Aniasi, A; Haworth, S E; Colombo, M B; Dimonopoli, T; Mocellin, M C; Poli, F; Torelli, R; Crespiatico, L; Serafini, M; Scalamogna, M

    2011-05-01

    The Italian Bone Marrow Donor Register is the institutional organization for management of unrelated hematopoietic stem cell donors. The law requires only a donor's clinical history, but not a psychosocial profile for registration. We have studied the donor's motivation for enlistment on the donor registry and the medical staff's need for this information to interact correctly with the donor. For this purpose we distributed a questionnaire to new donors at the 20 centers in the Lombardy Region over a period of 1 year. The analysis of the responses revealed a prevalence of extrinsic motivations that would not ensure continued registration for donation. Therefore, it is necessary that the donor be well informed and better educated about all aspects of donation, in order to produce a shift to an intrinsic motivation. This objective can be facilitated via professional training of health workers in communication. PMID:21620031

  6. Engraftment syndrome after allogeneic hematopoietic cell transplantation predicts poor outcomes.

    Science.gov (United States)

    Chang, Lawrence; Frame, David; Braun, Thomas; Gatza, Erin; Hanauer, David A; Zhao, Shuang; Magenau, John M; Schultz, Kathryn; Tokala, Hemasri; Ferrara, James L M; Levine, John E; Reddy, Pavan; Paczesny, Sophie; Choi, Sung Won

    2014-09-01

    Engraftment syndrome (ES), characterized by fever, rash, pulmonary edema, weight gain, liver and renal dysfunction, and/or encephalopathy, occurs at the time of neutrophil recovery after hematopoietic cell transplantation (HCT). In this study, we evaluated the incidence, clinical features, risk factors, and outcomes of ES in children and adults undergoing first-time allogeneic HCT. Among 927 patients, 119 (13%) developed ES at a median of 10 days (interquartile range 9 to 12) after HCT. ES patients experienced significantly higher cumulative incidence of grade 2 to 4 acute GVHD at day 100 (75% versus 34%, P HCT outcomes. Despite early recognition of the syndrome and prompt institution of corticosteroid therapy, outcomes in ES patients were uniformly poor. This study suggests the need for a prospective approach of collecting clinical features combined with correlative laboratory analyses to better characterize ES. PMID:24892262

  7. Natural Killer Cells Improve Hematopoietic Stem Cell Engraftment by Increasing Stem Cell Clonogenicity In Vitro and in a Humanized Mouse Model.

    Science.gov (United States)

    Escobedo-Cousin, Michelle; Jackson, Nicola; Laza-Briviesca, Raquel; Ariza-McNaughton, Linda; Luevano, Martha; Derniame, Sophie; Querol, Sergio; Blundell, Michael; Thrasher, Adrian; Soria, Bernat; Cooper, Nichola; Bonnet, Dominique; Madrigal, Alejandro; Saudemont, Aurore

    2015-01-01

    Cord blood (CB) is increasingly used as a source of hematopoietic stem cells (HSC) for transplantation. Low incidence and severity of graft-versus-host disease (GvHD) and a robust graft-versus-leukemia (GvL) effect are observed following CB transplantation (CBT). However, its main disadvantages are a limited number of HSC per unit, delayed immune reconstitution and a higher incidence of infection. Unmanipulated grafts contain accessory cells that may facilitate HSC engraftment. Therefore, the effects of accessory cells, particularly natural killer (NK) cells, on human CB HSC (CBSC) functions were assessed in vitro and in vivo. CBSC cultured with autologous CB NK cells showed higher levels of CXCR4 expression, a higher migration index and a higher number of colony forming units (CFU) after short-term and long-term cultures. We found that CBSC secreted CXCL9 following interaction with CB NK cells. In addition, recombinant CXCL9 increased CBSC clonogenicity, recapitulating the effect observed of CB NK cells on CBSC. Moreover, the co-infusion of CBSC with CB NK cells led to a higher level of CBSC engraftment in NSG mouse model. The results presented in this work offer the basis for an alternative approach to enhance HSC engraftment that could improve the outcome of CBT. PMID:26465138

  8. Natural Killer Cells Improve Hematopoietic Stem Cell Engraftment by Increasing Stem Cell Clonogenicity In Vitro and in a Humanized Mouse Model.

    Directory of Open Access Journals (Sweden)

    Michelle Escobedo-Cousin

    Full Text Available Cord blood (CB is increasingly used as a source of hematopoietic stem cells (HSC for transplantation. Low incidence and severity of graft-versus-host disease (GvHD and a robust graft-versus-leukemia (GvL effect are observed following CB transplantation (CBT. However, its main disadvantages are a limited number of HSC per unit, delayed immune reconstitution and a higher incidence of infection. Unmanipulated grafts contain accessory cells that may facilitate HSC engraftment. Therefore, the effects of accessory cells, particularly natural killer (NK cells, on human CB HSC (CBSC functions were assessed in vitro and in vivo. CBSC cultured with autologous CB NK cells showed higher levels of CXCR4 expression, a higher migration index and a higher number of colony forming units (CFU after short-term and long-term cultures. We found that CBSC secreted CXCL9 following interaction with CB NK cells. In addition, recombinant CXCL9 increased CBSC clonogenicity, recapitulating the effect observed of CB NK cells on CBSC. Moreover, the co-infusion of CBSC with CB NK cells led to a higher level of CBSC engraftment in NSG mouse model. The results presented in this work offer the basis for an alternative approach to enhance HSC engraftment that could improve the outcome of CBT.

  9. Response of hematopoietic stem cells to ionizing radiation

    International Nuclear Information System (INIS)

    Hematopoietic stem cells (HSCs) maintain blood and immune system throughout life and restore them after hematological injuries. Exposure of an organism to ionizing radiation (IR) causes rapid and acute myelosuppression and challenges the replenishment capacity of HSCs. Yet, the precise damages that are generated remain largely unexplored. To better understand these effects, phenotypic and functional changes in the stem/progenitor compartments of sublethally irradiated mice were monitored over a ten week period after radiation exposure. We report that shortly after sublethal IR-exposure, HSCs, defined by their repopulating ability, still segregate in the Hoechst dye excluding side population (SP); yet, their Sca-1 (S) and c-Kit (K) expression levels are increased and severely reduced, respectively, with a concurrent increase in the proportion of SPSK cells positive for established indicators of HSC presence: CD150+ and CD105+. A great proportion of HSCs quickly but transiently enter the cell cycle to replenish the bone marrow of myelo-ablated mice. Ten weeks after, whereas bone marrow cellularity has recovered and hematopoietic homeostasis is restored, major phenotypic modifications can be observed within the Lin-/low Sca-1+ c-Kit+ (LSK) stem/progenitor compartment: CD150+/Flk2- and CD150-/Flk2+ LSK cell frequencies are increased and dramatically reduced, respectively. CD150+ LSK cells also show impaired reconstitution capacity, accrued number of γ-H2AX foci and increased tendency to apoptosis. This demonstrates that the LSK compartment is not properly restored 10 weeks after sublethal exposure, and that long-term IR-induced injury to the bone marrow proceeds, at least partially, through direct damage to the stem cell pool. Thrombopoietin (TPO) has been shown to promote the survival of lethally irradiated mice when administrated quickly after exposure. We investigated the mechanisms underlying this effect, and found in a competitive transplant experiment that a

  10. Mouse Hematopoietic Stem Cells, Unlike Human and Mouse Embryonic Stem Cells, Exhibit Checkpoint–Apoptosis Coupling

    OpenAIRE

    Rohrabaugh, Sara; Mantel, Charlie; Broxmeyer, Hal E.

    2008-01-01

    Previously, we reported that the spindle assembly checkpoint (SAC), which is coupled in somatic cells, is uncoupled from apoptosis-initiation in mouse and human embryonic stem cells (ESCs). This condition allows ESCs to tolerate and proliferate as polyploidy/aneuploid cells. Proper function of the SAC is vital to prevent polyploidy/aneuploidy during ex vivo hematopoietic stem cell (HSC) expansion. Here we address, for the first time, whether HSCs are more like ESCs or somatic cells with respe...

  11. Application of autologous tumor cell vaccine and NDV vaccine in treatment of tumors of digestive tract

    Institute of Scientific and Technical Information of China (English)

    Wei Liang; Hui Wang; Tie-Mie Sun; Wen-Qing Yao; Li-Li Chen; Yu Jin; Chun-Ling Li; Fan-Juan Meng

    2003-01-01

    AIM: To treat patients with stage Ⅰ-Ⅳ malignant tumors of digestive tract using autologous tumor cell vaccine and NDV (Newcastle disease virus) vaccine, and observe the survival period and curative effect.METHODS: 335 patients with malignant tumors of digestive tract were treated with autologous tumor cell vaccine and NDV vaccine. The autologous tumor cell vaccine were assigned for long-term survival observation. While these failed to obtain the autologous tumor tissue were given with NDV vaccine for a short-term observation on curative effect.RESULTS: The colorectal cancer patients treated with autologous tumor cell vaccine were divided into two groups:the controlled group (subjected to resection alone) (n=257),the vaccine group (subjected to both resection and immunotherapy) (n=310). 25 patients treated with NDV immunotherapy were all at stage Ⅳ without having resection.In postoperation adjuvant therapy patients, the 5, 6 and 7-year survival rates were 66.51%, 60.52 %, 56.50 %respectively; whereas in patients with resection alone, only 45.57 %, 44.76 % and 43.42 % respectively. The average survival period was 5.13 years (resection alone group 4.15years), the median survival period was over 7 years (resection alone group 4.46 years). There were significant differences between the two groups. The patients treated with resection plus vaccine were measured delayed-type hypersensitivity (DTH) reactions after vaccination, (indurative scope >5 mm).The magnitude of DTH was related to the prognosis. The 5-year survival rate was 80 % for those with indurations greater than 5 mm, compared with 30 % for those with indurations less than 5 mm. The 1-year survival rate was 96 % for 25patients treated with NDV immunotherapy. The total effective rate (CR+PR) was 24.00 % in NDV immunotherapy; complete remission (CR) in 1 case (4.00 %), partial remission (PR) in 5 cases (20.00 %), stabilizedin in 16 cases (64.00 %),progression (PD) in 1 case (4.00 %). After NDV vaccine

  12. Hematopoietic stem cell transplantation activity worldwide in 2012 and a SWOT analysis of the Worldwide Network for Blood and Marrow Transplantation Group including the global survey.

    Science.gov (United States)

    Niederwieser, D; Baldomero, H; Szer, J; Gratwohl, M; Aljurf, M; Atsuta, Y; Bouzas, L F; Confer, D; Greinix, H; Horowitz, M; Iida, M; Lipton, J; Mohty, M; Novitzky, N; Nunez, J; Passweg, J; Pasquini, M C; Kodera, Y; Apperley, J; Seber, A; Gratwohl, A

    2016-06-01

    Data on 68 146 hematopoietic stem cell transplants (HSCTs) (53% autologous and 47% allogeneic) gathered by 1566 teams from 77 countries and reported through their regional transplant organizations were analyzed by main indication, donor type and stem cell source for the year 2012. With transplant rates ranging from 0.1 to 1001 per 10 million inhabitants, more HSCTs were registered from unrelated 16 433 donors than related 15 493 donors. Grafts were collected from peripheral blood (66%), bone marrow (24%; mainly non-malignant disorders) and cord blood (10%). Compared with 2006, an increase of 46% total (57% allogeneic and 38% autologous) was observed. Growth was due to an increase in reporting teams (18%) and median transplant activity/team (from 38 to 48 HSCTs/team). An increase of 167% was noted in mismatched/haploidentical family HSCT. A Strengths, Weaknesses, Opportunities, Threats (SWOT) analysis revealed the global perspective of WBMT to be its major strength and identified potential to be the key professional body for patients and authorities. The limited data collection remains its major weakness and threat. In conclusion, global HSCT grows over the years without plateauing (allogeneic>autologous) and at different rates in the four World Health Organization regions. Major increases were observed in allogeneic, haploidentical HSCT and, to a lesser extent, in cord blood transplantation. PMID:26901703

  13. High dose therapy with autologous stem cell support in malignant disorders

    International Nuclear Information System (INIS)

    New biomedical knowledge may improve the diagnostic procedures and treatment provided by the Health Services, but at additional cost. In a social democratic health care system, the hospital budgets have no room for expensive, new procedures or treatments, unless these are funded through extra allocation from the central authorities. High dose therapy with autologous stem cell support in malignant disorders is an example of a new and promising, but rather expensive treatment, but its role in cancer therapy has yet to be established. The indications for testing high dose therapy with autologous stem cell support in various malignancies are discussed, with emphasis on the principles for deciding which categories of disease should have priority. The authors suggest some malignant disorder for which high dose therapy with stem cell support should be explored versus conventional treatment in randomized prospective trials. 8 refs., 1 tab

  14. Donor Dependent Variations in Hematopoietic Differentiation among Embryonic and Induced Pluripotent Stem Cell Lines

    Science.gov (United States)

    Féraud, Olivier; Valogne, Yannick; Melkus, Michael W.; Zhang, Yanyan; Oudrhiri, Noufissa; Haddad, Rima; Daury, Aurélie; Rocher, Corinne; Larbi, Aniya; Duquesnoy, Philippe; Divers, Dominique; Gobbo, Emilie; Brunet de la Grange, Philippe; Louache, Fawzia; Bennaceur-Griscelli, Annelise; Mitjavila-Garcia, Maria Teresa

    2016-01-01

    Hematopoiesis generated from human embryonic stem cells (ES) and induced pluripotent stem cells (iPS) are unprecedented resources for cell therapy. We compared hematopoietic differentiation potentials from ES and iPS cell lines originated from various donors and derived them using integrative and non-integrative vectors. Significant differences in differentiation toward hematopoietic lineage were observed among ES and iPS. The ability of engraftment of iPS or ES-derived cells in NOG mice varied among the lines with low levels of chimerism. iPS generated from ES cell-derived mesenchymal stem cells (MSC) reproduce a similar hematopoietic outcome compared to their parental ES cell line. We were not able to identify any specific hematopoietic transcription factors that allow to distinguish between good versus poor hematopoiesis in undifferentiated ES or iPS cell lines. There is a relatively unpredictable variation in hematopoietic differentiation between ES and iPS cell lines that could not be predicted based on phenotype or gene expression of the undifferentiated cells. These results demonstrate the influence of genetic background in variation of hematopoietic potential rather than the reprogramming process. PMID:26938212

  15. DNA Damage: A Sensible Mediator of the Differentiation Decision in Hematopoietic Stem Cells and in Leukemia

    Directory of Open Access Journals (Sweden)

    Cary N. Weiss

    2015-03-01

    Full Text Available In the adult, the source of functionally diverse, mature blood cells are hematopoietic stem cells, a rare population of quiescent cells that reside in the bone marrow niche. Like stem cells in other tissues, hematopoietic stem cells are defined by their ability to self-renew, in order to maintain the stem cell population for the lifetime of the organism, and to differentiate, in order to give rise to the multiple lineages of the hematopoietic system. In recent years, increasing evidence has suggested a role for the accumulation of reactive oxygen species and DNA damage in the decision for hematopoietic stem cells to exit quiescence and to differentiate. In this review, we will examine recent work supporting the idea that detection of cell stressors, such as oxidative and genetic damage, is an important mediator of cell fate decisions in hematopoietic stem cells. We will explore the benefits of such a system in avoiding the development and progression of malignancies, and in avoiding tissue exhaustion and failure. Additionally, we will discuss new work that examines the accumulation of DNA damage and replication stress in aging hematopoietic stem cells and causes us to rethink ideas of genoprotection in the bone marrow niche.

  16. Studies of hematopoietic stem cells spared by 5-fluorouracil

    International Nuclear Information System (INIS)

    Mouse marrow cells were exposed to 5-fluorouracil (FU) either in vivo or in vitro and the effects on the hematopoietic stem cell compartment were studied. The drug was highly toxic to bone marrow cells including the spleen colony-forming unit (CFU-S) population. The small population of stem cells surviving FU, however, caused a different pattern of spleen colony growth when injected into lethally irradiated mice. Whereas numbers of spleen colonies caused by normal marrow cells remained constant during an 8-14 d period after transplantation, spleen colonies derived from FU-treated marrow cells increased by as much as 100-fold during this time. This effect on stem cells was dose dependent both in vitro and in vivo. When FU was given in vivo, the day 14/day 8 ratio of colonies was greatest 1 d after injection and, over the next 7 d, returned to a near-normal value, that is, unity. A number of studies have shown that the stem cell compartment is heterogeneous with respect to self-replicative capacity and developmental potential. An age structure for the stem cell compartment has been proposed wherein cells with a short mitotic history are more likely to self-replicate than they are to differentiate; hence they are more primitive. I propose that the delayed spleen colony appearance in normal hosts is the result of developmental maturation of the primitive stem cell compartment that survives FU and is responsible for spleen colonies arising around day 14. This maturation, at least initially, occurs in the marrow and leads to the replenishment of the more differentiated CFU-S subsets ablated by FU, which are normally responsible for spleen colonies appearing earlier after transplantation

  17. Pre-emptive treatment with rituximab of molecular relapse after autologous stem cell transplantation in mantle cell lymphoma

    DEFF Research Database (Denmark)

    Andersen, Niels S; Pedersen, Lone B; Laurell, Anna;

    2009-01-01

    PURPOSE: Minimal residual disease (MRD) is predictive of clinical progression in mantle-cell lymphoma (MCL). According to the Nordic MCL-2 protocol we prospectively analyzed the efficacy of pre-emptive treatment using rituximab to MCL patients in molecular relapse after autologous stem cell...

  18. Single-Cell Cytokine Profiling to Investigate Cellular Functional Diversity in Hematopoietic Malignancies.

    Science.gov (United States)

    Chen, Jonathan J; Kwak, Minsuk; Fan, Rong

    2016-01-01

    Single-cell analysis of cytokine production is increasingly recognized as an important method to understand the inflammatory microenvironment and hematopoietic disease state. Certain cytokines are critical to the regulation of lineage specification, and the aberrant production of these cytokines can contribute to lineage reprogramming. Here, we describe of a platform combining subnanoliter microchambers and a high-density antibody barcode array for the study of single-cell cytokine secretions in hematopoietic cancer cell populations. PMID:27581152

  19. Production of human glucocerebrosidase in mice after retroviral gene transfer into multipotential hematopoietic progenitor cells.

    OpenAIRE

    Correll, P H; Fink, J K; Brady, R O; Perry, L K; S. Karlsson

    1989-01-01

    The human glucocerebrosidase (GC) gene has been transferred efficiently into spleen colony-forming unit (CFU-S) multipotential hematopoietic progenitor cells, and production of human GC RNA and protein has been achieved in transduced CFU-S colonies. High-titer retroviral vectors containing the human GC cDNA were constructed. Mouse bone marrow cells were stimulated with hematopoietic growth factors, infected by coculture with producer cells, and injected into lethally irradiated animals. Four ...

  20. Expression Levels of Histone Deacetylases Determine the Cell Fate of Hematopoietic Progenitors*

    OpenAIRE

    Wada, Taeko; Kikuchi, Jiro; Nishimura, Noriko; Shimizu, Rumi; Kitamura, Toshio; Furukawa, Yusuke

    2009-01-01

    Histone deacetylases (HDACs) are globally implicated in the growth and differentiation of mammalian cells; however, relatively little is known about their specific roles in hematopoiesis. In this study, we investigated the expression of HDACs in human hematopoietic cells and their functions during hematopoiesis. The expression of HDACs was very low in hematopoietic progenitor cells, which was accompanied by histone hyperacetylation. HDACs were detectable in more differentiated progenitors and...

  1. Dysregulated Gene Expression During Hematopoietic Differentiation From Human Embryonic Stem Cells

    OpenAIRE

    Dravid, Gautam; Zhu, Yuhua; Scholes, Jessica; Evseenko, Denis; Crooks, Gay M

    2010-01-01

    The generation of hematopoietic cells from human embryonic stem cells (hESC) has raised the possibility of using hESC as an alternative donor source for transplantation. However, functional defects identified in hESC-derived cells limit their use for full lymphohematopoietic reconstitution. The purpose of the present study was to define and quantitate key functional and molecular differences between CD34+ hematopoietic progenitor subsets derived from hESC and CD34+ subsets from umbilical cord...

  2. Sox17 Dependence Distinguishes the Transcriptional Regulation of Fetal from Adult Hematopoietic Stem Cells

    OpenAIRE

    Kim, Injune; Saunders, Thomas L.; Morrison, Sean J

    2007-01-01

    Fetal stem cells differ phenotypically and functionally from adult stem cells in diverse tissues. However, little is known about how these differences are regulated. To address this we compared the gene expression profiles of fetal versus adult hematopoietic stem cells (HSCs) and discovered that the Sox17 transcriptional regulator is specifically expressed in fetal and neonatal but not adult HSCs. Germline deletion of Sox17 led to severe fetal hematopoietic defects, including a lack of detect...

  3. Mobilization of hematopoietic stem cells from the bone marrow niche to the blood compartment

    OpenAIRE

    Hoggatt, Jonathan; Pelus, Louis M.

    2011-01-01

    The vast majority of hematopoietic stem cells (HSCs) reside in specialized niches within the bone marrow during steady state, maintaining lifelong blood cell production. A small number of HSCs normally traffic throughout the body; however, exogenous stimuli can enhance their release from the niche and entry into the peripheral circulation. This process, termed mobilization, has become the primary means to acquire a stem cell graft for hematopoietic transplant at most transplant centers. Curre...

  4. Progress toward curing HIV infection with hematopoietic cell transplantation

    Directory of Open Access Journals (Sweden)

    Petz LD

    2015-07-01

    Full Text Available Lawrence D Petz,1 John C Burnett,2 Haitang Li,3 Shirley Li,3 Richard Tonai,1 Milena Bakalinskaya,4 Elizabeth J Shpall,5 Sue Armitage,6 Joanne Kurtzberg,7 Donna M Regan,8 Pamela Clark,9 Sergio Querol,10 Jonathan A Gutman,11 Stephen R Spellman,12 Loren Gragert,13 John J Rossi2 1StemCyte International Cord Blood Center, Baldwin Park, CA, USA; 2Department of Molecular and Cellular Biology, Irell and Manella Graduate School of Biological Sciences, 3Department of Molecular and Cellular Biology, Beckman Research Institute, City of Hope, Duarte, CA, USA; 4CCR5-Δ32/Δ32 Research Department, StemCyte International Cord Blood Center, Baldwin Park, CA, USA; 5Department of Stem Cell Transplantation, University of Texas MD Anderson Cancer Center, Houston, TX, USA; 6MD Anderson Cord Blood Bank, Department of Stem Cell Transplantation, University of Texas MD Anderson Cancer Center, Houston, TX, USA; 7Carolinas Cord Blood Bank, Duke University Medical Center, Durham, NC, USA; 8St Louis Cord Blood Bank, SSM Cardinal Glennon Children's Medical Center, St Louis, MO, USA; 9Enhance Quality Consulting Inc., Oviedo, FL, USA; 10Cell Therapy Service and Cord Blood Bank, Banc de Sang i Teixits, Barcelona, Spain; 11BMT/Hematologic Malignancies, University of Colorado, Aurora, CO, USA; 12Immunobiology and Observational Research, CIBMTR, Minneapolis, MN, USA; 13National Marrow Donor Program/Be The Match, Minneapolis, MN, USA Abstract: HIV-1 infection afflicts more than 35 million people worldwide, according to 2014 estimates from the World Health Organization. For those individuals who have access to antiretroviral therapy, these drugs can effectively suppress, but not cure, HIV-1 infection. Indeed, the only documented case for an HIV/AIDS cure was a patient with HIV-1 and acute myeloid leukemia who received allogeneic hematopoietic cell transplantation (HCT from a graft that carried the HIV-resistant CCR5-Δ32/Δ32 mutation. Other attempts to establish a cure for HIV

  5. HSC-explorer: a curated database for hematopoietic stem cells.

    Directory of Open Access Journals (Sweden)

    Corinna Montrone

    Full Text Available HSC-Explorer (http://mips.helmholtz-muenchen.de/HSC/ is a publicly available, integrative database containing detailed information about the early steps of hematopoiesis. The resource aims at providing fast and easy access to relevant information, in particular to the complex network of interacting cell types and molecules, from the wealth of publications in the field through visualization interfaces. It provides structured information on more than 7000 experimentally validated interactions between molecules, bioprocesses and environmental factors. Information is manually derived by critical reading of the scientific literature from expert annotators. Hematopoiesis-relevant interactions are accompanied with context information such as model organisms and experimental methods for enabling assessment of reliability and relevance of experimental results. Usage of established vocabularies facilitates downstream bioinformatics applications and to convert the results into complex networks. Several predefined datasets (Selected topics offer insights into stem cell behavior, the stem cell niche and signaling processes supporting hematopoietic stem cell maintenance. HSC-Explorer provides a versatile web-based resource for scientists entering the field of hematopoiesis enabling users to inspect the associated biological processes through interactive graphical presentation.

  6. A Rat Model of Autologous Oral Mucosal Epithelial Transplantation for Corneal Limbal Stem Cell Failure

    Institute of Scientific and Technical Information of China (English)

    Weihua Li; Qiaoli Li; Wencong Wang; Kaijing Li; Shiqi Ling; Yuanzhe Yang; Lingyi Liang

    2014-01-01

    Purpose:.To establish an animal model of autologous oral mucosa grafting for limbal stem cell deficiency. Methods:.The study was carried from August to October 2012. Fourteen SD rats were randomly and evenly allocated to study group A and control group B. Limbal stem cell defi-ciency was established by alkali burn in the right eye of each rat in both groups. Rats in group A received autologous oral mucosa strip transplantation following the chemical burn. Rats in group B did not receive surgery after the chemical burn. Topical antibiotics and dexamethasone were used in all rats. Corneal clarity,.corneal fluorescein staining,.oral mucosal graft survival, and complications at postoperative days 1,3,7, 14 were observed. Results:.The oral mucosa strip graft was detached in one rat in group A. Reepithelialization was observed starting from the graft position and was completed within 14 days in the re-maining 6 eyes in group A. However, persistent corneal ep-ithelium defect was observed in all eyes in group B, among which corneal melting and perforation was observed in 2 eyes and corneal opacification with neovascularization was ob-served in the remaining 5 eyes. Conclusion:.Autologous oral mucosa strip grafting for limbal stem cell deficiency can be achieved by a rat model following chemical burn. The fate of the transplanted oral mucosal ep-ithelial cells warrants further study. (Eye Science 2014; 29:1-5).

  7. Noncultured Autologous Adipose-Derived Stem Cells Therapy for Chronic Radiation Injury

    Directory of Open Access Journals (Sweden)

    Sadanori Akita

    2010-01-01

    Full Text Available Increasing concern on chronic radiation injuries should be treated properly for life-saving improvement of wound management and quality of life. Recently, regenerative surgical modalities should be attempted with the use of noncultured autologous adipose-derived stem cells (ADSCs with temporal artificial dermis impregnated and sprayed with local angiogenic factor such as basic fibroblast growth factor, and secondary reconstruction can be a candidate for demarcation and saving the donor morbidity. Autologous adipose-derived stem cells, together with angiogenic and mitogenic factor of basic fibroblast growth factor and an artificial dermis, were applied over the excised irradiated skin defect and tested for Patients who were uneventfully healed with minimal donor-site morbidity, which lasts more than 1.5 years.

  8. Human autologous serum as a substitute for fetal bovine serum in human Schwann cell culture.

    Directory of Open Access Journals (Sweden)

    Parisa Goodarzi

    2014-04-01

    Full Text Available Nowadays, cell -based and tissue engineered products have opened new horizons in treatment of incurable nervous system disorders. The number of studies on the role of Schwann cells (SC in treating nervous disorders is higher than other cell types. Different protocols have been suggested for isolation and expansion of SC which most of them have used multiple growth factors, mitogens and fetal bovine sera (FBS in culture medium. Because of potential hazards of animal-derived reagents, this study was designed to evaluate the effect of replacing FBS with human autologous serum (HAS on SC's yield and culture parameters. Samples from 10 peripheral nerve biopsies were retrieved and processed under aseptic condition. The isolated cells cultured in FBS (1st group or autologous serum (2nd group. After primary culture the cells were seeded at 10000 cell/cm2 in a 12 wells cell culture plate for each group. At 100% confluency, the cell culture parameters (count, viability, purity and culture duration of 2 groups were compared using paired t-test. The average donors' age was 35.80 (SD=13.35 and except for 1 sample the others cultured successfully. In first group, the averages of cell purity, viability and culture duration were 97% (SD=1.32, 97/33% (SD=1.22 and 11.77 (SD=2.58 days respectively. This parameters were 97.33% (SD=1.00, 97.55% (SD=1.33 and 10.33 days (SD=1.65 in second group. The difference of cell count, purity and viability were not significant between 2 groups (P>0.05. The cells of second group reached to 100% confluency in shorter period of time (P=0.03. The results of this study showed that autologous serum can be a good substitute for FBS in human SC culture. This can reduce the costs and improve the safety of cell product for clinical application.

  9. Autologous peripheral blood stem cell transplantation in children and adolescents with non-Hodgkin lymphoma

    OpenAIRE

    Gui, Wei; Su, Liping; He, Jianxia; WANG, LIEYANG; Guan, Tao

    2015-01-01

    The aim of this study was to evaluate the effect and safety of autologous peripheral blood stem cell transplantation (APBSCT) in children and adolescents with non-Hodgkin lymphoma (NHL). Ten patients with NHL were analyzed retrospectively. In all the patients, lymph node enlargement was most frequently detected. Patients with a mediastinal mass presented with a cough, palpitation and shortness of breath. Extranodal patients presented with abdominal pain, inability to walk and vaginal bleeding...

  10. Autologous Stem Cell Transplant Study in Lymphoma Patients: Statistical Analysis of Multi-State Models

    Czech Academy of Sciences Publication Activity Database

    Furstová, J.; Valenta, Zdeněk

    ISCB, 2012. s. 67-68. ISBN 978-82-8045-026-5. [Annual Conference of the International Society for Clinical Biostatistics /33./. 19.08.2012-23.08.2012, Bergen] Grant ostatní: ESF CZ.1.07/2.4.00/174.0117 Institutional support: RVO:67985807 Keywords : multi-state model * disability model * illness-death model * Markov model * autologous stem cell transplant Subject RIV: BB - Applied Statistics, Operational Research

  11. 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.

  12. Late Effects Surveillance Recommendations among Survivors of Childhood Hematopoietic Cell Transplantation: A Children's Oncology Group Report.

    Science.gov (United States)

    Chow, Eric J; Anderson, Lynnette; Baker, K Scott; Bhatia, Smita; Guilcher, Gregory M T; Huang, Jennifer T; Pelletier, Wendy; Perkins, Joanna L; Rivard, Linda S; Schechter, Tal; Shah, Ami J; Wilson, Karla D; Wong, Kenneth; Grewal, Satkiran S; Armenian, Saro H; Meacham, Lillian R; Mulrooney, Daniel A; Castellino, Sharon M

    2016-05-01

    Hematopoietic cell transplantation (HCT) is an important curative treatment for children with high-risk hematologic malignancies, solid tumors, and, increasingly, nonmalignant diseases. Given improvements in care, there are a growing number of long-term survivors of pediatric HCT. Compared with childhood cancer survivors who did not undergo transplantation, HCT survivors have a substantially increased burden of serious chronic conditions and impairments involving virtually every organ system and overall quality of life. This likely reflects the joint contributions of pretransplantation treatment exposures and organ dysfunction, the transplantation conditioning regimen, and any post-transplantation graft-versus-host disease (GVHD). In response, the Children's Oncology Group (COG) has created long-term follow-up guidelines (www.survivorshipguidelines.org) for survivors of childhood, adolescent, and young adult cancer, including those who were treated with HCT. Guideline task forces, consisting of HCT specialists, other pediatric oncologists, radiation oncologists, organ-specific subspecialists, nurses, social workers, other health care professionals, and patient advocates systematically reviewed the literature with regards to late effects after childhood cancer and HCT since 2002, with the most recent review completed in 2013. For the most recent review cycle, over 800 articles from the medical literature relevant to childhood cancer and HCT survivorship were reviewed, including 586 original research articles. Provided herein is an organ system-based overview that emphasizes the most relevant COG recommendations (with accompanying evidence grade) for the long-term follow-up care of childhood HCT survivors (regardless of current age) based on a rigorous review of the available evidence. These recommendations cover both autologous and allogeneic HCT survivors, those who underwent transplantation for nonmalignant diseases, and those with a history of chronic GVHD. PMID

  13. Subclinical hypothyroidism in children and adolescents after hematopoietic stem cells transplantation without irradiation

    Directory of Open Access Journals (Sweden)

    Milenković Tatjana

    2014-01-01

    Full Text Available Background/Aim. Although total body irradiation (TBI was considered to be the primary cause of thyroid dysfunction following hematopoietic stem cells transplantation (HSCT, a significant prevalence of subclinical hypothyroidism after HSCT with chemotherapy-only conditioning regimens has been observed in several studies. The aim of this study was to assess changes in thyroid stimulating hormone (TSH levels in children after HSCT, without the use of irradiation at any time in the course of the treatment. Methods. Our cohort consisted of 41 children and adolescents who underwent autologous or allogeneic HSCT and were available for follow-up for at least one year after transplantation. Irradiation was not performed in any of the subjects, neither during pretransplatation therapy, nor during conditioning. The median duration of follow-up was 2.9 years. The indications for HSCT were hematologic malignancy (41.5%, solid malignant tumor (34.1%, and other disorders (24.4%. The thyroid status of all the subjects was assessed prior to HSCT and after follow-up period. Results. Thyroid dysfunction after HSCT was present in 27 (65.8% subjects. Subclinical hypothyroidism was the most common abnormality, presenting in 23 (56.1% patients, primary hypothyroidism was present in one (2.4% patient, while 3 (7.3% subjects had low free T4 with normal TSH values. Significantly (p < 0.01 higher elevations in TSH levels were present in the patients who received chemotherapy for the underlying disease prior to HSCT. Conclusion. Our findings emphasize the need for long-term monitoring of thyroid function following HSCT, regardless of whether or not irradiation was used.

  14. The Changing Epidemiology of Bloodstream Infections and Resistance in Hematopoietic Stem Cell Transplantation Recipients

    Directory of Open Access Journals (Sweden)

    Mücahit Yemişen

    2016-08-01

    Full Text Available Objective: Patients receiving hematopoietic stem cell transplantation (HSCT are exposed to highly immunosuppressive conditions and bloodstream infections (BSIs are one of the most common major complications within this period. Our aim, in this study, was to evaluate the epidemiology of BSIs in these patients retrospectively. Materials and Methods: The epidemiological properties of 312 patients with HSCT were retrospectively evaluated. Results: A total of 312 patients, followed between 2000 and 2011, who underwent autologous (62% and allogeneic (38% HSCT were included in the study. The most common underlying malignancies were multiple myeloma (28% and Hodgkin lymphoma (21.5%. A total of 142 (45% patients developed at least 1 episode of BSI and 193 separate pathogens were isolated from the blood cultures. There was a trend of increase in the numbers of BSIs in 2005-2008 and a relative increase in the proportion of gram-positive infections in recent years (2009-2011, and central venous catheter-related BSI was found to be most common source. Coagulase-negative staphylococci (49.2% and Acinetobacter baumannii (8.8% were the most common pathogens. Extended-spectrum beta-lactamase-producing strains were 23% and 22% among Escherichia coli and Klebsiella spp. isolates, respectively. Quinolone resistance was detected in 10% of Enterobacteriaceae. Resistance to carbapenems was not detected in Enterobacteriaceae, while it was seen at 11.1% and 23.5% in Pseudomonas and Acinetobacter strains, respectively. Conclusion: A shift was detected from gram-negative bacteria to gram-positive in the etiology over the years and central lines were the most common sources of BSIs.

  15. 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.

  16. Immunophenotyping of hematopoietic progenitor cells: Comparison between cord blood and adult mobilized blood grafts

    OpenAIRE

    2011-01-01

    AIM: To study the immunophenotype of hematopoietic progenitor cells from cord blood (CB) grafts (n = 39) in comparison with adult apheresis grafts (AG, n = 229) and pre-apheresis peripheral blood (PAPB) samples (n = 908) using flow cytometry analysis.

  17. Expression of human adenosine deaminase in mice reconstituted with retrovirus-transduced hematopoietic stem cells

    International Nuclear Information System (INIS)

    Recombinant retroviruses encoding human adenosine deaminase have been used to infect murine hematopoietic stem cells. In bone marrow transplant recipients reconstituted with the genetically modified cells, human ADA was detected in peripheral blood mononuclear cells of the recipients for at least 6 months after transplantation. In animals analyzed in detail 4 months after transplantation, human ADA and proviral sequences were detected in all hematopoietic lineages; in several cases, human ADA activity exceeded the endogenous activity. These studies demonstrate the feasibility of introducing a functional human ADA gene into hematopoietic stem cells and obtaining expression in multiple hematopoietic lineages long after transplantation. This approach should be helpful in designing effective gene therapies for severe combined immunodeficiency syndromes in humans

  18. The role of citrulline in patients following hematopoietic stem cell transplantation

    NARCIS (Netherlands)

    Herbers, A.H.E.

    2015-01-01

    Hematopoietic stem cell transplantation (HSCT) provides effective treatment of hematological malignancies and other disorders. However, the procedure temporarily compromises the immune system resulting in damage to the gastrointestinal (GI) tract, called mucosal barrier injury (MBI), and neutropenia

  19. Characterization of Selectin Ligands on Hematopoietic Stem Cells

    KAUST Repository

    Mahmood, Hanan

    2013-05-18

    Successful bone marrow (BM) transplantation requires the homing of the transplanted hematopoietic stem/progenitor cells (HSPCs) to their bone marrow niche, where they undergo differentiation to form mature cells that are eventually released into the peripheral blood. However, the survival rate of patients receiving BM transplants is poor since many of the transplanted HSPCs do not make it to their BM niches in the recipient’s body. Since the availability of HSPCs from traditional sources is limited, transplanting more number of HSPCs is not a solution to this problem. This study aims to characterize the adhesion molecules mediating cell migration in order to better understand the adhesion mechanisms of HSCs with the bone marrow endothelium. This will aid in developing future tools to improve the clinical transplantation of HSPCs. This study also aims to understand the factors that influence HSPC proliferation in the bone marrow niche. E-selectin plays an important role in the process of homing; however, its ligands on HSPCs are not well characterized. We used western blotting and immunoprecipitation to show that endomucin is expressed on HSPCs and plays a role in the binding of HSPCs to E-selectin. We also studied the effect of recombinant E-selectin on the expression of a newly characterized E-selectin ligand in our lab, CD34, in HSPCs. This will provide us insight into novel roles for endomucin and E-selectin and help us to understand the factors influencing HSPC migration to BM endothelium.

  20. Identification of a population of cells with hematopoietic stem cell properties in mouse aorta-gonad-mesonephros cultures

    International Nuclear Information System (INIS)

    The aorta-gonad-mesonephros (AGM) region is a primary source of definitive hematopoietic cells in the midgestation mouse embryo. In cultures of dispersed AGM regions, adherent cells containing endothelial cells are observed first, and then non-adherent hematopoietic cells are produced. Here we report on the characterization of hematopoietic cells that emerge in the AGM culture. Based on the expression profiles of CD45 and c-Kit, we defined three cell populations: CD45low c-Kit+ cells that had the ability to form hematopoietic cell colonies in methylcellulose media and in co-cultures with stromal cells; CD45low c-Kit- cells that showed a granulocyte morphology; CD45high c-Kitlow/- that exhibited a macrophage morphology. In co-cultures of OP9 stromal cells and freshly prepared AGM cultures, CD45low c-Kit+ cells from the AGM culture had the abilities to reproduce CD45low c-Kit+ cells and differentiate into CD45low c-Kit- and CD45high c-Kitlow/- cells, whereas CD45low c-Kit- and CD45high c-Kitlow/- did not produce CD45low c-Kit+ cells. Furthermore, CD45low c-Kit+ cells displayed a long-term repopulating activity in adult hematopoietic tissue when transplanted into the liver of irradiated newborn mice. These results indicate that CD45low c-Kit+ cells from the AGM culture have the potential to reconstitute multi-lineage hematopoietic cells

  1. Regulatory T cells and immune tolerance after allogeneic hematopoietic stem cell transplantation

    NARCIS (Netherlands)

    M. Bruinsma (Marieke)

    2010-01-01

    textabstractThe story of allogeneic hematopoietic stem cell transplantation (allo-SCT) begins after the atomic bombings of Hiroshima and Nagasaki in 1945. It was observed that fallout radiation caused dose-dependent depression of hematopoiesis 1. Research first focused on how to protect the hematopo

  2. Immune Reconstitution after Allogeneic Hematopoietic Cell Transplantation in Children.

    Science.gov (United States)

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

    2016-02-01

    Allogeneic (allo) hematopoietic cell transplantation (HCT) has evolved into a potent curative treatment option for a variety of malignant and nonmalignant diseases. The occurrence of complications and mortality after allo-HCT is, however, still high and is strongly associated with immune reconstitution (IR). Therefore, detailed information on IR through immunomonitoring is crucial to improve survival chances after HCT. To date, information about the reconstituting immune system after allo-HCT in pediatric patients is mostly derived from routine standard-of-care measurements. More profound knowledge on IR may provide tools to better predict and modulate adverse reactions and, subsequently, improve survival chances. Here, we provide an overview of IR (eg, immune cell subsets and circulating chemokines/cytokines) after allo-HCT in children, taking into account different cell sources and serotherapy, and discuss strategies to enhance immunomonitoring. We conclude that available IR data after allo-HCT contain limited information on immune cell families (mostly only generic T, B, and NK cells), which would improve with more detailed information on reconstituting cell subsets or effector cell functionality at earlier time points (functionality and may even provide (early) biomarkers for individual disease outcome, such as viral reactivity, graft-versus-host disease, or graft-versus-leukemia. The present data and suggestions for more detailed, standardized, and harmonized immunomonitoring in future (pediatric) allo-HCT studies will pave the path to "precision transplantation:" an individualized HCT approach (including conditioning), based on detailed information on IR and biomarkers, aiming to reduce transplantation related mortality and relapse, and subsequently improve survival chances. PMID:26341398

  3. Mesenchymal stem cell derived hematopoietic cells are permissive to HIV-1 infection

    Directory of Open Access Journals (Sweden)

    Mondal Debasis

    2011-01-01

    Full Text Available Abstract Background Tissue resident mesenchymal stem cells (MSCs are multipotent, self-renewing cells known for their differentiation potential into cells of mesenchymal lineage. The ability of single cell clones isolated from adipose tissue resident MSCs (ASCs to differentiate into cells of hematopoietic lineage has been previously demonstrated. In the present study, we investigated if the hematopoietic differentiated (HD cells derived from ASCs could productively be infected with HIV-1. Results HD cells were generated by differentiating clonally expanded cultures of adherent subsets of ASCs (CD90+, CD105+, CD45-, and CD34-. Transcriptome analysis revealed that HD cells acquire a number of elements that increase their susceptibility for HIV-1 infection, including HIV-1 receptor/co-receptor and other key cellular cofactors. HIV-1 infected HD cells (HD-HIV showed elevated p24 protein and gag and tat gene expression, implying a high and productive infection. HD-HIV cells showed decreased CD4, but significant increase in the expression of CCR5, CXCR4, Nef-associated factor HCK, and Vpu-associated factor BTRC. HIV-1 restricting factors like APOBEC3F and TRIM5 also showed up regulation. HIV-1 infection increased apoptosis and cell cycle regulatory genes in HD cells. Although undifferentiated ASCs failed to show productive infection, HIV-1 exposure increased the expression of several hematopoietic lineage associated genes such as c-Kit, MMD2, and IL-10. Conclusions Considering the presence of profuse amounts of ASCs in different tissues, these findings suggest the possible role that could be played by HD cells derived from ASCs in HIV-1 infection. The undifferentiated ASCs were non-permissive to HIV-1 infection; however, HIV-1 exposure increased the expression of some hematopoietic lineage related genes. The findings relate the importance of ASCs in HIV-1 research and facilitate the understanding of the disease process and management strategies.

  4. Cell-surface expression of Hsp70 on hematopoietic cancer cells after inhibition of HDAC activity

    DEFF Research Database (Denmark)

    Jensen, Helle; Andresen, Lars; Hansen, Karen Aagaard; Skov, Søren

    2009-01-01

    We show that inhibition of HDAC activity leads to surface expression of Hsp70 on various hematopoietic cancer cells, an occurance that was not observed on naïve or activated peripheral blood cells. HDAC inhibitor-mediated Hsp70 surface expression was confined to the apoptotic Annexin V...... activity selectively induces surface expression of Hsp70 on hematopoietic cancer cells and that this may increase immunorecognition of these cells.......-positive cells and blocked by inhibition of apoptosis. Other chemotherapeutic inducers of apoptosis such as etoposide and camptothecin also led to a robust induction of Hsp70 surface expression. Hsp70 expression was, however, not caused by induction of apoptosis per se, as activated CD4 T cells remained Hsp70...

  5. Critical Role of Jak2 in the Maintenance and Function of Adult Hematopoietic Stem Cells

    OpenAIRE

    Akada, Hajime; Akada, Saeko; Hutchison, Robert E.; Sakamoto, Kazuhito; Wagner, Kay-Uwe; Mohi, Golam

    2014-01-01

    Jak2, a member of the Janus kinase family of non-receptor protein tyrosine kinases, is activated in response to a variety of cytokines, and functions in survival and proliferation of cells. An activating JAK2V617F mutation has been found in most patients with myeloproliferative neoplasms, and patients treated with Jak2 inhibitors show significant hematopoietic toxicities. However, the role of Jak2 in adult hematopoietic stem cells (HSCs) has not been clearly elucidated. Using a conditional Ja...

  6. Myelodysplastic syndrome evolving from aplastic anemia treated with immunosuppressive therapy: efficacy of hematopoietic stem cell transplantation

    OpenAIRE

    Kim, Sung-Yong; Le Rademacher, Jennifer; Antin, Joseph H.; Anderlini, Paolo; Ayas, Mouhab; Battiwalla, Minoo; Carreras, Jeanette; Kurtzberg, Joanne; Nakamura, Ryotaro; Eapen, Mary; Deeg, H. Joachim

    2014-01-01

    A proportion of patients with aplastic anemia who are treated with immunosuppressive therapy develop clonal hematologic disorders, including post-aplastic anemia myelodysplastic syndrome. Many will proceed to allogeneic hematopoietic stem cell transplantation. We identified 123 patients with post-aplastic anemia myelodysplastic syndrome who from 1991 through 2011 underwent allogeneic hematopoietic stem cell transplantation, and in a matched-pair analysis compared outcome to that in 393 patien...

  7. Quality of life of hospitalized patients submitted to hematopoietic stem cells transplantation

    OpenAIRE

    Vanessa da Rocha; Luciana Puchalski Kalinke; Jorge Vinicius Cestari Felix; Maria de Fátima Montovani; Mariluci Alves Maftum; Paulo Ricardo Bittencourt Guimarães

    2015-01-01

    The objective of this study was to assess the quality of life and to identify the altered domains of adult patients with blood cancer, submitted to hematopoietic stem cells transplantation during hospitalization time. A longitudinal, observation and analytical study, conducted in a reference hospital for hematopoietic stem cell transplant. The data collection was during September of 2013 and September of 2014, including 25 patients and using questionnaires for sociodemographic and clinic char...

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

    OpenAIRE

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

    2013-01-01

    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 se...

  9. Are neural crest stem cells the missing link between hematopoietic and neurogenic niches?

    Directory of Open Access Journals (Sweden)

    Virginie Neirinckx

    2015-06-01

    Full Text Available Hematopoietic niches are defined as cellular and molecular microenvironments that regulate hematopoietic stem cell (HSC function together with stem cell autonomous mechanisms. Many different cell types have been characterized as contributors to the formation of HSC niches, such as osteoblasts, endothelial cells, Schwann cells, and mesenchymal progenitors. These mesenchymal progenitors have themselves been classified as CXC chemokine ligand (CXCL12-abundant reticular (CAR cells, stem cell factor expressing cells, or nestin-positive mesenchymal stem cells (MSCs, which have been recently identified as neural crest-derived cells (NCSCs. Together, these cells are spatially associated with HSCs and believed to provide appropriate microenvironments for HSC self-renewal, differentiation, mobilization and hibernation both by cell-to-cell contact and soluble factors. Interestingly, it appears that regulatory pathways governing the hematopoietic niche homeostasis are operating in the neurogenic niche as well. Therefore, this review paper aims to compare both the regulation of hematopoietic and neurogenic niches, in order to highlight the role of NCSCs and nervous system components in the development and the regulation of the hematopoietic system.

  10. Are neural crest stem cells the missing link between hematopoietic and neurogenic niches?

    Science.gov (United States)

    Coste, Cécile; Neirinckx, Virginie; Gothot, André; Wislet, Sabine; Rogister, Bernard

    2015-01-01

    Hematopoietic niches are defined as cellular and molecular microenvironments that regulate hematopoietic stem cell (HSC) function together with stem cell autonomous mechanisms. Many different cell types have been characterized as contributors to the formation of HSC niches, such as osteoblasts, endothelial cells, Schwann cells, and mesenchymal progenitors. These mesenchymal progenitors have themselves been classified as CXC chemokine ligand (CXCL) 12-abundant reticular (CAR) cells, stem cell factor expressing cells, or nestin-positive mesenchymal stem cells (MSCs), which have been recently identified as neural crest-derived cells (NCSCs). Together, these cells are spatially associated with HSCs and believed to provide appropriate microenvironments for HSC self-renewal, differentiation, mobilization and hibernation both by cell-cell contact and soluble factors. Interestingly, it appears that regulatory pathways governing the hematopoietic niche homeostasis are operating in the neurogenic niche as well. Therefore, this review paper aims to compare both the regulation of hematopoietic and neurogenic niches, in order to highlight the role of NCSCs and nervous system components in the development and the regulation of the hematopoietic system. PMID:26136659

  11. Paracrine Molecules of Mesenchymal Stem Cells for Hematopoietic Stem Cell Niche

    OpenAIRE

    Tian Li; Yaojiong Wu

    2011-01-01

    Hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) are both adult stem cells residing in the bone marrow. MSCs interact with HSCs, they stimulate and enhance the proliferation of HSCs by secreting regulatory molecules and cytokines, providing a specialized microenvironment for controlling the process of hematopoiesis. In this paper we discuss how MSCs contribute to HSC niche, maintain the stemness and proliferation of HSCs, and support HSC transplantation.

  12. The treatment of diffuse cutaneous systemic sclerosis with autologous hemopoietic stem cells transplantation (HSCT: our experience on 2 cases

    Directory of Open Access Journals (Sweden)

    A. Tyndall

    2011-09-01

    Full Text Available Objectives: Autologous hematopoietic stem cell transplantation (HSCT is a treatment option which may be considered for severe diffuse cutaneous systemic sclerosis (dcSSc patients not responding to cyclophophamide (CY. We present two cases of dcSSc not responding to CY >10 g who were successfully treated with HSCT. Patients and methods: Two dcSSc patients were unresponsive to monthly i.v. pulse of CYC (0.75 g m2. Both patients had significant reduction of DLCO and mild-moderate pulmonary hypertension and HSCT was considered due to the rapid progression of the disease. Following informed consent and ethics committee approval, HSCT was performed. Mobilisation was performed with CY 4g/m2 and recombinant human granulocyte colony stimulating factor (rHu GCSF followed by a successful apheresis (CD34+ cells, >7X106. Conditioning regimens were: CY 100mg/kg body weight plus thiotepa 10 mg/ kg in the first patient and CY 200 mg/kg in the second. Both graft products were CD34 selected. No arrythmias occurred during the procedure and no other severe side effects were observed during hospitalisation. Results: Follow up: Patients underwent a monthly follow up with physical examination, pulmonary function tests and echocardiography every 3 months. Chest CT has been performed 6 months post transplantation. The following was observed: skin score (from 40 to 10 for the first patient and from 38 to 12 for the second one, LVEF and pulmonary function remained stable, PAP decreased from 45 mmHg to 35 mmHg and from 40 to 32 mmHg. No late complications or cardiac toxicity was observed. Conclusion: These two dcSSc cases demonstrate that HSCT may be successfully performed without serious side effects in cases in whom despite a cumulative CY dose was ineffective. This suggests an “immunological threshold” effect which may be exploited in other severe, therapy refractory autoimmune cases.

  13. Improved Activation toward Primary Colorectal Cancer Cells by Antigen-Specific Targeting Autologous Cytokine-Induced Killer Cells

    Directory of Open Access Journals (Sweden)

    Claudia Schlimper

    2012-01-01

    Full Text Available Adoptive therapy of malignant diseases with cytokine-induced killer (CIK cells showed promise in a number of trials; the activation of CIK cells from cancer patients towards their autologous cancer cells still needs to be improved. Here, we generated CIK cells ex vivo from blood lymphocytes of colorectal cancer patients and engineered those cells with a chimeric antigen receptor (CAR with an antibody-defined specificity for carcinoembryonic antigen (CEA. CIK cells thereby gained a new specificity as defined by the CAR and showed increase in activation towards CEA+ colon carcinoma cells, but less in presence of CEA− cells, indicated by increased secretion of proinflammatory cytokines. Redirected CIK activation was superior by CAR-mediated CD28-CD3ζ than CD3ζ signaling only. CAR-engineered CIK cells from colon carcinoma patients showed improved activation against their autologous, primary carcinoma cells from biopsies resulting in more efficient tumour cell lysis. We assume that adoptive therapy with CAR-modified CIK cells shows improved selectivity in targeting autologous tumour lesions.

  14. Alternative donor hematopoietic cell transplantation for Fanconi anemia.

    Science.gov (United States)

    MacMillan, Margaret L; DeFor, Todd E; Young, Jo-Anne H; Dusenbery, Kathryn E; Blazar, Bruce R; Slungaard, Arne; Zierhut, Heather; Weisdorf, Daniel J; Wagner, John E

    2015-06-11

    Historically, alternative donor hematopoietic cell transplantation (HCT) for Fanconi anemia (FA) patients resulted in excessive morbidity and mortality. To improve outcomes, we made sequential changes to the HCT conditioning regimen. A total of 130 FA patients (median age, 9.0 years; range, 1-48) underwent alternative donor HCT at the University of Minnesota between 1995 and 2012. All patients received cyclophosphamide (CY), single fraction total body irradiation (TBI), and antithymocyte globulin (ATG) with or without fludarabine (FLU), followed by T-cell-depleted bone marrow or unmanipulated umbilical cord blood transplantation. The addition of FLU enhanced engraftment 3-fold. The incidence of grades 2-4 acute and chronic graft-versus-host disease was 20% and 10%, respectively. Severe toxicity was highest in patients >10 years of age or those with a history of opportunistic infections or transfusions before HCT. Mortality was lowest in patients without a history of opportunistic infection or transfusions and who received conditioning with TBI 300 cGy, CY, FLU, and ATG. These patients had a probability of survival of 94% at 5 years. Alternative donor HCT is now associated with excellent survival for patients without prior opportunistic infections or transfusions and should be considered for all FA patients after the onset of marrow failure. These studies were registered at http://www.clinicaltrials.gov as NCT00005898, NCT00167206, and NCT00352976. PMID:25824692

  15. TET2 deficiency inhibits mesoderm and hematopoietic differentiation in human embryonic stem cells

    DEFF Research Database (Denmark)

    Langlois, Thierry; da Costa Reis Monte Mor, Barbara; Lenglet, Gaëlle;

    2014-01-01

    profile, including abnormal expression of neuronal genes. Intriguingly, when TET2 was knockdown in hematopoietic cells, it increased hematopoietic development. In conclusion, our work suggests that TET2 is involved in different stages of human embryonic development, including induction of the mesoderm and......Ten-Eleven-Translocation 2 (TET2) belongs to the TET protein family that catalyzes the conversion of 5-methylcytosine into 5-hydroxymethylcytosine and plays a central role in normal and malignant adult hematopoiesis. Yet, the role of TET2 in human hematopoietic development remains largely unknown....... Here, we show that TET2 expression is low in human embryonic stem (ES) cell lines and increases during hematopoietic differentiation. ShRNA-mediated TET2 knockdown had no effect on the pluripotency of various ES cells. However, it skewed their differentiation into neuroectoderm at the expense of...

  16. Platelet-rich plasma-induced bone marrow mesenchymal stem cells versus autologous nerve grafting for sciatic nerve repair

    Institute of Scientific and Technical Information of China (English)

    Changsuo Xia; Yajuan Li; Wen Cao; Zhaohua Yu

    2010-01-01

    Autologous nerve grafting is the gold standard of peripheral nerve repair.We previously showed that autologous platelet-rich plasma(PRP)contains high concentrations of growth factors and can induce in vitro cultured bone marrow mesenchymal stem cells(BMSCs)to differentiate into Schwann cells.Here we used PRP-induced BMSCs combined with chemically extracted acellular nerves to repair sciatic nerve defects and compared the effect with autologous nerve grafting.The BMSCs and chemically extracted acellular nerve promoted target muscle wet weight restoration,motor nerve conduction velocity,and axonal and myelin sheath regeneration,with similar effectiveness to autologous nerve grafting.This finding suggests that PRP induced BMSCs can be used to repair peripheral nerve defects.

  17. Regulatory Systems in Bone Marrow for Hematopoietic Stem/Progenitor Cells Mobilization and Homing

    Directory of Open Access Journals (Sweden)

    P. Alvarez

    2013-01-01

    Full Text Available Regulation of hematopoietic stem cell release, migration, and homing from the bone marrow (BM and of the mobilization pathway involves a complex interaction among adhesion molecules, cytokines, proteolytic enzymes, stromal cells, and hematopoietic cells. The identification of new mechanisms that regulate the trafficking of hematopoietic stem/progenitor cells (HSPCs cells has important implications, not only for hematopoietic transplantation but also for cell therapies in regenerative medicine for patients with acute myocardial infarction, spinal cord injury, and stroke, among others. This paper reviews the regulation mechanisms underlying the homing and mobilization of BM hematopoietic stem/progenitor cells, investigating the following issues: (a the role of different factors, such as stromal cell derived factor-1 (SDF-1, granulocyte colony-stimulating factor (G-CSF, and vascular cell adhesion molecule-1 (VCAM-1, among other ligands; (b the stem cell count in peripheral blood and BM and influential factors; (c the therapeutic utilization of this phenomenon in lesions in different tissues, examining the agents involved in HSPCs mobilization, such as the different forms of G-CSF, plerixafor, and natalizumab; and (d the effects of this mobilization on BM-derived stem/progenitor cells in clinical trials of patients with different diseases.

  18. Role of Hematopoietic Stem Cells in Inflammation of the Pancreas during Diabetes Mellitus.

    Science.gov (United States)

    Dygai, A M; Skurikhin, E G; Pershina, O V; Ermakova, N N; Krupin, V A; Ermolaeva, L A; Stakheeva, M N; Choinzonov, E L; Goldberg, V E; Reikhart, D V; Ellinidi, V N; Kravtsov, V Yu

    2016-02-01

    The model of streptozotocin-induced diabetes mellitus in C57Bl/6 mice was employed to study the role of precursors of insulin-producing β-cells, hematopoietic stem cells, and progenitor hematopoietic cells in inflammation. In addition to provoking hyperglycemia, streptozotocin elevated serum levels of IL-1β and hyaluronic acid, induced edema in the pancreatic insular tissue and its infiltration by inflammatory cells (neutrophils, lymphocytes, and macrophages) and fibroblasts. Inflammation in pancreatic islets was accompanied by necrotic processes and decreasing counts of multipotent progenitor β-cells (CD45(-), TER119(-), c-kit-1(-), and Flk-1(-)), oligopotent progenitor β-cells (CD45(-), TER119(-), CD133(+), and CD49f(low)), and insulinproducing β-cells (Pdx1(+)). Pancreatic infl ammation was preceded by elevation of the number of short-term hematopoietic stem cells (Lin-Sca-1(+)c-kit(+)CD34(+)) relative to long-term cells (Lin(-)Sca-1(+)c-kit(+)CD34(-)) in the bone marrow as well as recruitment of hematopoietic stem and progenitor cells into circulation. Transplantation of bone marrow hematopoietic stem and progenitor cells from diabetic C57Bl/6 donor mice to recipient CBA mice with 5-fluorouracilinduced leukopenia accelerated regeneration of granulocytopoiesis in recipient mice. PMID:26906195

  19. The autologous bone marrow mononuclear cell transplantation by intracoronary route treat patients with severe heart failure after myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    高连如

    2006-01-01

    Objective To investigate the chronic effects of intracoronary autologous bone marrow mononuclear cell (BM-MNCs) transplantation in patients with refractory heart failure (RIHF) after myocardial infarction. Methods Thirty patients with RIHF (LVEF<40%) were enrolled in this nonrandomized study, autologous BM-MNCs (5.0±0.7)×107 were transplanted with via infarct-related coronary artery in 16 patients and 14 patients received

  20. Optimising gene therapy of hypoparathyroidism with hematopoietic stem cells

    Institute of Scientific and Technical Information of China (English)

    ZHOU Yi; L(U) Bing-jie; XU Ping; SONG Chun-fang

    2005-01-01

    Background The treatment of hypoparathyroidism (HPT) is still a difficult clinical problem, which necessitates a new therapy. Gene therapy of HPT has been valuable, but how to improve the gene transfer efficiency and expression stability is a problem. This study was designed to optimize the gene therapy of HPT with hematopoietic stem cells (HSCs) recombined with the parathyroid hormone (PTH) gene. Methods The human PTH gene was amplified by polymerase chain reaction (PCR) from pcDNA3.1-PTH vectors and inserted into murine stem cell virus (MSCV) vectors with double enzyme digestion (EcoRI and XhoI). The recombinant vectors were transfected into PA317 packaging cell lines by the lipofectin method and screened by G418 selective medium. The condensed recombinant retroviruses were extracted and used to infect HSCs, which were injected into mice suffering from HPT. The change of symptoms and serum levels of PTH and calcium in each group of mice were investigated. Results The human PTH gene was inserted into MSCV vectors successfully and the titres were up to 2×107 colony forming unit (CFU)/ml in condensed retroviral solution. The secretion of PTH reached 15 ng·10-6·cell-1 per 48 hours. The wild type viruses were not detected via PCR amplification, so they were safe for use. The mice suffering from HPT recovered quickly and the serum levels of calcium and PTH remained normal for about three months after the HSCs recombined with PTH were injected into them. The therapeutic effect of this method was better than simple recombinant retroviruses injection.Conclusions The recombinant retroviral vectors MSCV-PTH and the high-titre condensed retroviral solution recombined with the PTH gene are obtained. The recombinant retroviral solution could infect HSCs at a high rate of efficiency. The infected HSCs could cure HPT in mice. This method has provided theoretical evidence for the clinical gene therapy of HPT.

  1. Placental Growth Factor Expression Is Required for Bone Marrow Endothelial Cell Support of Primitive Murine Hematopoietic Cells

    OpenAIRE

    Xiaoying Zhou; Barsky, Lora W.; Adams, Gregor B

    2013-01-01

    Two distinct microenvironmental niches that regulate hematopoietic stem/progenitor cell physiology in the adult bone marrow have been proposed; the endosteal and the vascular niche. While extensive studies have been performed relating to molecular interactions in the endosteal niche, the mechanisms that regulate hematopoietic stem/progenitor cell interaction with bone marrow endothelial cells are less well defined. Here we demonstrate that endothelial cells derived from the bone marrow suppor...

  2. Autologous bone marrow stem cells--properties and advantages.

    Science.gov (United States)

    Rice, Claire M; Scolding, Neil J

    2008-02-15

    The properties of self-renewal and multi-lineage differentiation make stem cells attractive candidates for use in cellular reparative therapy, particularly in neurological diseases where there is a paucity of treatment options. However, clinical trials using foetal material in Parkinson's disease have been disappointing and highlighted problems associated with the use of embryonic stem cells, including ethical issues and practical concerns regarding teratoma formation. Understandably, this has led investigators to explore alternative sources of stem cells for transplantation. The expression of neuroectodermal markers by cells of bone marrow origin focused attention on these adult stem cells. Although early enthusiasm has been tempered by dispute regarding the validity of reports of in vitro (trans)differentiation, the demonstration of functional benefit in animal models of neurological disease is encouraging. Here we will review some of the required properties of stem cells for use in transplantation therapy with specific reference to the development of bone marrow-derived cells as a source of cells for repair in demyelination. PMID:17669432

  3. [Neutrophil disorders: diagnosis and hematopoietic stem cell transplantation].

    Science.gov (United States)

    Kobayashi, Masao

    2015-10-01

    Neutrophil disorders are classified into abnormal neutrophil function and granulopoiesis. The identification of genetic defects causing neutropenia and neutrophil dysfunction has revealed the mechanisms controlling myeloid differentiation and their functions. The International Union of Immunological Societies of Primary Immunodeficiencies represents the most current catalog of approximately 30 neutrophil disorders. In this report, we show the progress made in studies of the pathophysiology and treatment of these disorders, focusing on chronic granulomatous disease (CGD) and severe congenital neutropenia (SCN). Hematopoietic stem cell transplantation (HSCT) is the only available curative therapy for CGD and SCN. However, the use of HSCT as treatment for both diseases is limited by transplant-related mortality (TRM) because of active infections and intractable inflammatory complications. Recently, reduced-intensity conditioning regimens have been introduced to minimize the TRM and the late adverse effects of HSCT for both diseases. The results of HSCT using the RIC regimen for 40 patients with CGD and SCN in Hiroshima University Hospital are summarized herein. Determining the optimal line of treatment will require further accumulation to cases to refine HSCT for both diseases. PMID:26458464

  4. Systematic Nutritional Support in Allogeneic Hematopoietic Stem Cell Transplant Recipients.

    Science.gov (United States)

    Fuji, Shigeo; Einsele, Hermann; Savani, Bipin N; Kapp, Markus

    2015-10-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) has become an established treatment modality for various hematological diseases. However, in allogeneic HSCT, patients often suffer from severe gastrointestinal complications caused by the conditioning regimen and acute/chronic graft-versus-host disease, which requires support by multidisciplinary nutritional support teams (NST). In addition, pretransplantation nutritional status can affect the clinical outcome after allogeneic HSCT. Therefore, it is important to refer the patient to a NST when becoming aware of nutritional problems before allogeneic HSCT. It is also important to follow nutritional status over the long term, as patients often suffer from various nutritional problems, such as malnutrition and metabolic syndrome, even late after allogeneic HSCT. In summary, NST can contribute to the improvement of nutritional status and possibly prognosis at every stage before and after allogeneic HSCT. Here, we aim to give a comprehensive overview of current understanding about nutritional support in allogeneic HSCT and try to provoke a constructive discussion to stimulate further investigation. PMID:26172477

  5. HEMATOPOIETIC CELL TRANSPLANTATION FOR OLDER PATIENTS WITH MDS

    Directory of Open Access Journals (Sweden)

    Mazyar Shadman

    2014-09-01

    Full Text Available The incidence of myeloid malignancies, including myelodysplastic syndromes (MDS increases with age. While several therapeutic modalities have been developed, for most of these patients the only treatment with curative potential is allogeneic hematopoietic cell transplantation (HCT. The development of reduced/low intensity transplant conditioning regimens allows to successfully transplant patients in their ‘60s and even ‘70s, although comorbidities may determine who does come to transplantation and who does not. Also, as many as half of the patients will develop graft versus host disease (GVHD, even with HLA matched  donors, requiring therapy for extended periods of time,  and GVHD and treatment  with glucocorticoids is likely to impact the quality  of life. Nevertheless, dependent upon disease stage at HCT, the presence of comorbidities and the regimen used, 30% to 50% of patients  60 years of age or older, may survive long-term cured of their disease. Future studies should focus on the incorporation of non-transplant modalities into the overall transplant approach, the prevention of GVHD, and the utilization of immunotherapy to reduce the incidence of relapse and GVHD and further improve overall transplant success.

  6. Eltrombopag for Treatment of Thrombocytopenia after Allogeneic Hematopoietic Cell Transplantation.

    Science.gov (United States)

    Tanaka, Takashi; Inamoto, Yoshihiro; Yamashita, Takuya; Fuji, Shigeo; Okinaka, Keiji; Kurosawa, Saiko; Kim, Sung-Won; Tanosaki, Ryuji; Fukuda, Takahiro

    2016-05-01

    Persistent thrombocytopenia is a common complication after allogeneic hematopoietic cell transplantation (HCT). Eltrombopag is an oral thrombopoietin receptor agonist whose efficacy against persistent thrombocytopenia after allogeneic HCT has not been well characterized. This retrospective study evaluated the safety and efficacy of eltrombopag in 12 consecutive patients with persistent thrombocytopenia after allogeneic HCT. Eltrombopag was started at 12.5 mg once daily and the dose was increased by 12.5 mg daily every week until platelet counts exceeded 50,000/μL. Five patients had prolonged isolated thrombocytopenia (PIT) and 7 patients had secondary failure of platelet recovery (SFPR). The cumulative incidence rate of successful platelet recovery to ≥50,000/μL without transfusion support was 60% in PIT patients and 71% in SFPR patients. No patients discontinued the drug because of adverse events or intolerability. Notably, the rate of platelet recovery was higher (100% versus 58%; P = .0017) and recovery was faster (median, 33 days versus 137 days; P = .0078) in patients with normal numbers of bone marrow megakaryocytes before starting eltrombopag than in those with decreased numbers of megakaryocytes. Eltrombopag is a promising treatment for both PIT and SFPR after allogeneic HCT. The number of megakaryocytes in bone marrow before eltrombopag treatment may predict the response to eltrombopag. PMID:26785333

  7. 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

  8. Hematopoietic Cell Transplantation for Acute Lymphoblastic Leukemia in Adults.

    Science.gov (United States)

    Speziali, Craig; Paulson, Kristjan; Seftel, Matthew

    2016-06-01

    The majority of adults with acute lymphoblastic leukemia will achieve a first complete remission (CR). However relapse is the most common cause of treatment failure. Outcomes after relapse remain poor, with long-term survival in the order of 10 %. Treatment decisions made at the time of first complete remission are thus critical to ensuring long-term survival. Allogeneic hematopoietic cell transplant (HCT) is effective at preventing relapse in many transplant recipients but is also associated with significant treatment related morbidity and mortality. Alternatively, ongoing systemic chemotherapy offers lower toxicity at the expense of increased relapse rates. Over the past decades, both the safety of transplant and the efficacy of non-transplant chemotherapy have improved. Emerging data show substantially improved outcomes for young adults treated with pediatric-inspired chemotherapy regimens that question the role of HCT in the upfront setting. In this review, we review the data supporting the role of allogeneic transplantation in adult acute lymphoblastic leukemia (ALL), and we propose a therapeutic algorithm for upfront therapy of adults with ALL. PMID:26984203

  9. Comparative study of hematopoietic differentiation between human embryonic stem cell lines.

    Science.gov (United States)

    Melichar, Heather; Li, Ou; Ross, Jenny; Haber, Hilary; Cado, Dragana; Nolla, Hector; Robey, Ellen A; Winoto, Astar

    2011-01-01

    Directed differentiation of human embryonic stem cells (hESCs) into any desired cell type has been hailed as a therapeutic promise to cure many human diseases. However, substantial roadblocks still exist for in vitro differentiation of hESCs into distinct cell types, including T lymphocytes. Here we examined the hematopoietic differentiation potential of six different hESC lines. We compare their ability to develop into CD34(+) or CD34(+)CD45(+) hematopoietic precursor populations under several differentiation conditions. Comparison of lymphoid potential of hESC derived- and fetal tissue derived-hematopoietic precursors was also made. We found diverse hematopoietic potential between hESC lines depending on the culture or passage conditions. In contrast to fetal-derived hematopoietic precursors, none of the CD34(+) precursors differentiated from hESCs were able to develop further into T cells. These data underscore the difficulties in the current strategy of hESC forward differentiation and highlight distinct differences between CD34(+) hematopoietic precursors generated in vitro versus in vivo. PMID:21603627

  10. Comparative study of hematopoietic differentiation between human embryonic stem cell lines.

    Directory of Open Access Journals (Sweden)

    Heather Melichar

    Full Text Available Directed differentiation of human embryonic stem cells (hESCs into any desired cell type has been hailed as a therapeutic promise to cure many human diseases. However, substantial roadblocks still exist for in vitro differentiation of hESCs into distinct cell types, including T lymphocytes. Here we examined the hematopoietic differentiation potential of six different hESC lines. We compare their ability to develop into CD34(+ or CD34(+CD45(+ hematopoietic precursor populations under several differentiation conditions. Comparison of lymphoid potential of hESC derived- and fetal tissue derived-hematopoietic precursors was also made. We found diverse hematopoietic potential between hESC lines depending on the culture or passage conditions. In contrast to fetal-derived hematopoietic precursors, none of the CD34(+ precursors differentiated from hESCs were able to develop further into T cells. These data underscore the difficulties in the current strategy of hESC forward differentiation and highlight distinct differences between CD34(+ hematopoietic precursors generated in vitro versus in vivo.

  11. Canine PHA-stimulated adherent cell enhance interferon-gamma production and proliferation of autologous peripheral blood mononuclear cells.

    Science.gov (United States)

    Ide, Kaori; Momoi, Yasuyuki; Iwasaki, Toshiroh

    2005-03-01

    Dendritic cells are specialized antigen-presenting cells with immuno-modulating functions that are attractive for clinical applications for cancer immunotherapy. This study examined immunostimulatory functions of phytohemagglutinin (PHA)-stimulated adherent cells (PHA-Ad cells) from peripheral blood mononuclear cells (PBMCs) in dogs. PHA-Ad cells enhanced interferon-gamma from autologous PBMC in vitro. PHA-Ad cells also stimulated antigen-independent proliferation of peripheral blood lymphocytes. These results suggest that PHA-Ad cells from PBMC possess a stimulatory function to evoke anti-tumour immunity and that they demonstrate potential for therapeutic applications in dogs. PMID:19379211

  12. EXERCISE in pediatric autologous stem cell transplant patients: a randomized controlled trial protocol

    OpenAIRE

    Chamorro-Viña Carolina; Guilcher Gregory MT; Khan Faisal M; Mazil Karen; Schulte Fiona; Wurz Amanda; Williamson Tanya; Reimer Raylene A; Culos-Reed S Nicole

    2012-01-01

    Abstract Background Hematopoietic stem cell transplantation is an intensive therapy used to improve survivorship and cure various oncologic diseases. However, this therapy is associated with high mortality rates and numerous negative side-effects. The recovery of the immune system is a special concern and plays a key role in the success of this treatment. In healthy populations it is known that exercise plays an important role in immune system regulation, but little is known about the role of...

  13. OP9-Lhx2 stromal cells facilitate derivation of hematopoietic progenitors both in vitro and in vivo.

    Science.gov (United States)

    Chen, Xiaoli; Zhao, Qianhao; Li, Chen; Geng, Yang; Huang, Ke; Zhang, Jian; Wang, Xiaoshan; Yang, Jiaqi; Wang, Tongjie; Xia, Chengxiang; Liu, Xiaofei; Meng, Minghui; Yang, Dan; Zheng, Yi; Du, Juan; Zhang, Xiangzhong; Chen, Jiekai; Pan, Guangjin; Wang, Jinyong

    2015-09-01

    Generating engraftable hematopoietic stem cells (HSCs) from pluripotent stem cells (PSCs) is an ideal approach for obtaining induced HSCs for cell therapy. However, the path from PSCs to robustly induced HSCs (iHSCs) in vitro remains elusive. We hypothesize that the modification of hematopoietic niche cells by transcription factors facilitates the derivation of induced HSCs from PSCs. The Lhx2 transcription factor is expressed in fetal liver stromal cells but not in fetal blood cells. Knocking out Lhx2 leads to a fetal hematopoietic defect in a cell non-autonomous role. In this study, we demonstrate that the ectopic expression of Lhx2 in OP9 cells (OP9-Lhx2) accelerates the hematopoietic differentiation of PSCs. OP9-Lhx2 significantly increased the yields of hematopoietic progenitor cells via co-culture with PSCs in vitro. Interestingly, the co-injection of OP9-Lhx2 and PSCs into immune deficient mice also increased the proportion of hematopoietic progenitors via the formation of teratomas. The transplantation of phenotypic HSCs from OP9-Lhx2 teratomas but not from the OP9 control supported a transient repopulating capability. The upregulation of Apln gene by Lhx2 is correlated to the hematopoietic commitment property of OP9-Lhx2. Furthermore, the enforced expression of Apln in OP9 cells significantly increased the hematopoietic differentiation of PSCs. These results indicate that OP9-Lhx2 is a good cell line for regeneration of hematopoietic progenitors both in vitro and in vivo. PMID:26339946

  14. OP9-Lhx2 stromal cells facilitate derivation of hematopoietic progenitors both in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Xiaoli Chen

    2015-09-01

    Full Text Available Generating engraftable hematopoietic stem cells (HSCs from pluripotent stem cells (PSCs is an ideal approach for obtaining induced HSCs for cell therapy. However, the path from PSCs to robustly induced HSCs (iHSCs in vitro remains elusive. We hypothesize that the modification of hematopoietic niche cells by transcription factors facilitates the derivation of induced HSCs from PSCs. The Lhx2 transcription factor is expressed in fetal liver stromal cells but not in fetal blood cells. Knocking out Lhx2 leads to a fetal hematopoietic defect in a cell non-autonomous role. In this study, we demonstrate that the ectopic expression of Lhx2 in OP9 cells (OP9-Lhx2 accelerates the hematopoietic differentiation of PSCs. OP9-Lhx2 significantly increased the yields of hematopoietic progenitor cells via co-culture with PSCs in vitro. Interestingly, the co-injection of OP9-Lhx2 and PSCs into immune deficient mice also increased the proportion of hematopoietic progenitors via the formation of teratomas. The transplantation of phenotypic HSCs from OP9-Lhx2 teratomas but not from the OP9 control supported a transient repopulating capability. The upregulation of Apln gene by Lhx2 is correlated to the hematopoietic commitment property of OP9-Lhx2. Furthermore, the enforced expression of Apln in OP9 cells significantly increased the hematopoietic differentiation of PSCs. These results indicate that OP9-Lhx2 is a good cell line for regeneration of hematopoietic progenitors both in vitro and in vivo.

  15. Maternal T cells limit engraftment after in utero hematopoietic cell transplantation in mice

    OpenAIRE

    Nijagal, Amar; Wegorzewska, Marta; Jarvis, Erin; Le, Tom; Tang, Qizhi; MacKenzie, Tippi C.

    2011-01-01

    Transplantation of allogeneic stem cells into the early gestational fetus, a treatment termed in utero hematopoietic cell transplantation (IUHCTx), could potentially overcome the limitations of bone marrow transplants, including graft rejection and the chronic immunosuppression required to prevent rejection. However, clinical use of IUHCTx has been hampered by poor engraftment, possibly due to a host immune response against the graft. Since the fetal immune system is relatively immature, we h...

  16. Allogeneic hematopoietic stem cell transplantation for primary cutaneous T cell lymphomas

    OpenAIRE

    Paralkar, Vikram R.; Nasta, Sunita Dwivedy; Morrissey, Kelly; Smith, Jacqueline; Vassilev, Pavel; Martin, Mary Ellen; Goldstein, Steven C.; Loren, Alison; Rook, Alain H.; Kim, Ellen J.; Porter, David L.

    2011-01-01

    Cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of non-Hodgkin lymphomas that are considered incurable. The role of allogeneic hematopoietic stem cell transplantation (HSCT) in the treatment of CTCL is not well defined but may provide potent graft-vs-lymphoma (GVL) activity independent of the conditioning therapy. We present outcomes of 12 extensively-pretreated patients with CTCL who underwent allogeneic HSCT using, most commonly, a reduced intensity conditioning (RIC) regimen. M...

  17. Regulatory T-cell immunotherapy for allogeneic hematopoietic stem-cell transplantation

    OpenAIRE

    Horch, Matthew; Nguyen, Vu H

    2012-01-01

    From mouse studies to recently published clinical trials, evidence has accumulated on the potential use of regulatory T cells (Treg) in preventing and treating graft-versus-host disease following hematopoietic-cell transplantation (HCT). However, controversies remain as to the phenotype and stability of various Treg subsets and their respective roles in vivo, the requirement of antigen-specificity of Treg to reduce promiscuous suppression, and the molecular mechanisms by which Treg suppress, ...

  18. Transcatheter Arterial Infusion of Autologous CD133+ Cells for Diabetic Peripheral Artery Disease

    Science.gov (United States)

    Zhang, Xiaoping; Lian, Weishuai; Lou, Wensheng; Han, Shilong; Lu, Chenhui; Zuo, Keqiang; Su, Haobo; Xu, Jichong; Cao, Chuanwu; Tang, Tao; Jia, Zhongzhi; Jin, Tao; Uzan, Georges; Gu, Jianping; Li, Maoquan

    2016-01-01

    Microvascular lesion in diabetic peripheral arterial disease (PAD) still cannot be resolved by current surgical and interventional technique. Endothelial cells have the therapeutic potential to cure microvascular lesion. To evaluate the efficacy and immune-regulatory impact of intra-arterial infusion of autologous CD133+ cells, we recruited 53 patients with diabetic PAD (27 of CD133+ group and 26 of control group). CD133+ cells enriched from patients' PB-MNCs were reinfused intra-arterially. The ulcer healing followed up till 18 months was 100% (3/3) in CD133+ group and 60% (3/5) in control group. The amputation rate was 0 (0/27) in CD133+ group and 11.54% (3/26) in control group. Compared with the control group, TcPO2 and ABI showed obvious improvement at 18 months and significant increasing VEGF and decreasing IL-6 level in the CD133+ group within 4 weeks. A reducing trend of proangiogenesis and anti-inflammatory regulation function at 4 weeks after the cells infusion was also found. These results indicated that autologous CD133+ cell treatment can effectively improve the perfusion of morbid limb and exert proangiogenesis and anti-inflammatory immune-regulatory impacts by paracrine on tissue microenvironment. The CD133+ progenitor cell therapy may be repeated at a fixed interval according to cell life span and immune-regulatory function. PMID:26981134

  19. Cigarette Smoke Alters the Hematopoietic Stem Cell Niche

    Directory of Open Access Journals (Sweden)

    Robert W. Siggins

    2014-02-01

    Full Text Available Effects of tobacco smoke on hematologic derangements have received little attention. This study employed a mouse model of cigarette smoke exposure to explore the effects on bone marrow niche function. While lung cancer is the most widely studied consequence of tobacco smoke exposure, other malignancies, including leukemia, are associated with tobacco smoke exposure. Animals received cigarette smoke exposure for 6 h/day, 5 days/week for 9 months. Results reveal that the hematopoietic stem and progenitor cell (HSPC pool size is reduced by cigarette smoke exposure. We next examined the effect of cigarette smoke exposure on one supporting cell type of the niche, the mesenchymal stromal cells (MSCs. Smoke exposure decreased the number of MSCs. Transplantation of naïve HSPCs into irradiated mice with cigarette smoke exposure yielded fewer numbers of engrafted HSPCs. This result suggests that smoke-exposed mice possess dysfunctional niches, resulting in abnormal hematopoiesis. Co-culture experiments using MSCs isolated from control or cigarette smoke-exposed mice with naïve HSPCs in vitro showed that MSCs from cigarette smoke-exposed mice generated marked expansion of naïve HSPCs. These data show that cigarette smoke exposure decreases in vivo MSC and HSC number and also increases pro-proliferative gene expression by cigarette smoke-exposed MSCs, which may stimulate HSPC expansion. These results of this investigation are clinically relevant to both bone marrow donors with a history of smoking and bone marrow transplant (BMT recipients with a history of smoking.

  20. Tissue Engineering Bone Using Autologous Progenitor Cells in the Peritoneum

    OpenAIRE

    Jinhui Shen; Ashwin Nair; Ramesh Saxena; Cheng Cheng Zhang; Joseph Borrelli; Liping Tang

    2014-01-01

    Despite intensive research efforts, there remains a need for novel methods to improve the ossification of scaffolds for bone tissue engineering. Based on a common phenomenon and known pathological conditions of peritoneal membrane ossification following peritoneal dialysis, we have explored the possibility of regenerating ossified tissue in the peritoneum. Interestingly, in addition to inflammatory cells, we discovered a large number of multipotent mesenchymal stem cells (MSCs) in the periton...

  1. Vector design for expression of O6-methylguanine-DNA methyltransferase in hematopoietic cells

    OpenAIRE

    Schambach, Axel; Baum, Christopher

    2007-01-01

    Enhancing DNA repair activity of hematopoietic cells by stably integrating gene vectors that express O(6)-methylguanine-DNA-methyltransferase (MGMT) is of major interest for innovative approaches in tumor chemotherapy and for the control of hematopoietic chimerism in the treatment of multiple other acquired or inherited disorders. Crucial determinants of this selection principle are the stringency of treatment with O(6)-alkylating agents and the level of transgenic MGMT expression. Attempts t...

  2. Donor parity no longer a barrier for female-to-male hematopoietic stem cell transplantation

    OpenAIRE

    van Halteren, Astrid GS; Miranda P Dierselhuis; Netelenbos, Tanja; Fechter, Mirjam

    2014-01-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) is a widely applied treatment for disorders mainly involving the hematopoietic system. The success of this treatment depends on many different patient- and donor-specific factors. Based on higher CD34+ yields and superior clinical outcomes associated with the use of male donors, males are generally seen as the preferred HSCT donor. In addition, female donors are notorious for bearing memory type lymphocytes induced by previous pregnanc...

  3. In Vivo Repopulating Activity Emerges at the Onset of Hematopoietic Specification during Embryonic Stem Cell Differentiation

    OpenAIRE

    Stella Pearson; Sara Cuvertino; Maud Fleury; Georges Lacaud; Valerie Kouskoff

    2015-01-01

    Summary The generation of in vivo repopulating hematopoietic cells from in vitro differentiating embryonic stem cells has remained a long-standing challenge. To date, hematopoietic engraftment has mostly been achieved through the enforced expression of ectopic transcription factors. Here, we describe serum-free culture conditions that allow the generation of in vivo repopulating hematopoietic cells in the absence of ectopically expressed factors. We show that repopulating activity arises imme...

  4. High-dose immunosuppression and hematopoietic stem cell transplantation in autoimmune disease: clinical review.

    Science.gov (United States)

    Openshaw, Harry; Nash, Richard A; McSweeney, Peter A

    2002-01-01

    Since 1996, a number of investigators have carried out phase I-II studies of high-dose immunosuppression with autologous hematopoietic stem cell transplantation (HSCT) in autoimmune diseases. Most of this activity has been in studies of multiple sclerosis (MS), systemic sclerosis (SSc), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and juvenile idiopathic arthritis (JIA). Supported by animal models of antigen-induced autoimmunity, the rationale of HSCT is to time-shift the clinical autoimmunity to an earlier period, restoring self-tolerance. Even with the considerable experience of more than 200 transplantations since 1996, it is difficult to judge the optimal approach. This difficulty is in part because of the multiplicity of centers and protocols and the variability in patient eligibility and assessment, the extent of T-cell depletion, and the intensity of the preparatory regimens used. Other than that found in RA, treatment-related mortality has been higher than expected: 17% in SSc (with an additional 10% mortality from progressive disease), 13% in SLE, 13% in JIA, and 8% in MS. Protocol changes to improve safety have been instituted. These changes include the avoidance of high-dose rabbit antithymocyte serum in patients who received T-cell-depleted grafts, use of corticosteroids with granulocyte colony-stimulating factor during stem cell mobilization and as prophylaxis for the engraftment syndrome in MS, lung radiation shielding in SSc, and multiple precautions against the macrophage activation syndrome in JIA. Responses to primary and secondary endpoints have been seen, and there is a consensus among investigators and regulatory bodies that the time has come for randomized phase II-III studies. Each disease presents distinct difficulties: in MS, restriction of eligibility to patients with active inflammatory disease; in SSc, formulation of cardiopulmonary eligibility criteria to decrease risk; in SLE, judgment of whether HSCT adds any

  5. Reconstitution of mammary epithelial morphogenesis by murine embryonic stem cells undergoing hematopoietic stem cell differentiation.

    Directory of Open Access Journals (Sweden)

    Shuxian Jiang

    Full Text Available BACKGROUND: Mammary stem cells are maintained within specific microenvironments and recruited throughout lifetime to reconstitute de novo the mammary gland. Mammary stem cells have been isolated through the identification of specific cell surface markers and in vivo transplantation into cleared mammary fat pads. Accumulating evidence showed that during the reformation of mammary stem cell niches by dispersed epithelial cells in the context of the intact epithelium-free mammary stroma, non-mammary epithelial cells may be sequestered and reprogrammed to perform mammary epithelial cell functions and to adopt mammary epithelial characteristics during reconstruction of mammary epithelium in regenerating mammary tissue in vivo. METHODOLOGY/PRINCIPAL FINDINGS: To examine whether other types of progenitor cells are able to contribute to mammary branching morphogenesis, we examined the potential of murine embryonic stem (mES cells, undergoing hematopoietic differentiation, to support mammary reconstitution in vivo. We observed that cells from day 14 embryoid bodies (EBs under hematopoietic differentiation condition, but not supernatants derived from these cells, when transplanted into denuded mammary fat pads, were able to contribute to both the luminal and myoepithelial lineages in branching ductal structures resembling the ductal-alveolar architecture of the mammary tree. No teratomas were observed when these cells were transplanted in vivo. CONCLUSIONS/SIGNIFICANCE: Our data provide evidence for the dominance of the tissue-specific mammary stem cell niche and its role in directing mES cells, undergoing hematopoietic differentiation, to reprogram into mammary epithelial cells and to promote mammary epithelial morphogenesis. These studies should also provide insights into regeneration of damaged mammary gland and the role of the mammary microenvironment in reprogramming cell fate.

  6. Autologous bone marrow cell therapy for peripheral arterial disease

    Directory of Open Access Journals (Sweden)

    Botti C

    2012-09-01

    Full Text Available C Botti, C Maione, A Coppola, V Sica, G CobellisDepartment of General Pathology, Second University of Naples, Naples, ItalyAbstract: Inadequate blood supply to tissues caused by obstruction of arterioles and/or capillaries results in ischemic injuries – these injuries can range from mild (eg, leg ischemia to severe conditions (eg, myocardial infarction, stroke. Surgical and/or endovascular procedures provide cutting-edge treatment for patients with vascular disorders; however, a high percentage of patients are currently not treatable, owing to high operative risk or unfavorable vascular involvement. Therapeutic angiogenesis has recently emerged as a promising new therapy, promoting the formation of new blood vessels by the introduction of bone marrow–derived stem and progenitor cells. These cells participate in the development of new blood vessels, the enlargement of existing blood vessels, and sprouting new capillaries from existing blood vessels, providing evidence of the therapeutic utility of these cells in ischemic tissues. In this review, the authors describe peripheral arterial disease, an ischemic condition affecting the lower extremities, summarizing different aspects of vascular regeneration and discussing which and how stem cells restore the blood flow. The authors also present an overview of encouraging results from early-phase clinical trials using stem cells to treat peripheral arterial disease. The authors believe that additional research initiatives should be undertaken to better identify the nature of stem cells and that an intensive cooperation between laboratory and clinical investigators is needed to optimize the design of cell therapy trials and to maximize their scientific rigor. Only this will allow the results of these investigations to develop best clinical practices. Additionally, although a number of stem cell therapies exist, many treatments are performed outside international and national regulations and many

  7. 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.

  8. Autologous hematopoietic stem cell transplantation (AHSCT) for aggressive multiple sclerosis - whom, when and how.

    Science.gov (United States)

    Szczechowski, Lech; Śmiłowski, Marek; Helbig, Grzegorz; Krawczyk-Kuliś, Małgorzata; Kyrcz-Krzemień, Sławomira

    2016-10-01

    Multiple sclerosis (MS) is an autoimmune disease of the central nervous system that leads to an inflammatory process resulting in demyelination and axonal degeneration. The most common form of MS is the relapsing-remitting MS (RRMS) characterized by the presence of numerous relapses. After few years of disease course, 90% of those patients eventually develop a secondary progressive form. About 10% of patients may suffer from a slowly progressive MS form - the primary progressive. The current treatment of RRMS includes immunomodulatory and immunosuppressive agents, which are effective, but usually in earlier and more benign forms. The immunomodulatory treatment has limited efficacy in aggressive forms of RRMS, and relapses occur despite treatment continuation. AHSCT should be considered as a therapeutic approach for patients with aggressive relapsing-remitting and aggressive progressive MS who failed conventional therapy. The mechanism of action of AHSCT for MS results from resetting the aberrant patient's immune system and eliminating the autoreactive T-lymphocytes. AHSCT can serve as an effective and safe procedure only when strict neurological eligibility criteria are adhered. The procedure should be performed in highly specialized hematological centers. The aim of our paper is to summarize the current eligibility criteria for AHSCT in MS patients as well as to present data on efficacy and safety of this approach. PMID:26577419

  9. Aneuploidy impairs hematopoietic stem cell fitness and is selected against in regenerating tissues in vivo.

    Science.gov (United States)

    Pfau, Sarah J; Silberman, Rebecca E; Knouse, Kristin A; Amon, Angelika

    2016-06-15

    Aneuploidy, an imbalanced karyotype, is a widely observed feature of cancer cells that has long been hypothesized to promote tumorigenesis. Here we evaluate the fitness of cells with constitutional trisomy or chromosomal instability (CIN) in vivo using hematopoietic reconstitution experiments. We did not observe cancer but instead found that aneuploid hematopoietic stem cells (HSCs) exhibit decreased fitness. This reduced fitness is due at least in part to the decreased proliferative potential of aneuploid hematopoietic cells. Analyses of mice with CIN caused by a hypomorphic mutation in the gene Bub1b further support the finding that aneuploidy impairs cell proliferation in vivo. Whereas nonregenerating adult tissues are highly aneuploid in these mice, HSCs and other regenerative adult tissues are largely euploid. These findings indicate that, in vivo, mechanisms exist to select against aneuploid cells. PMID:27313317

  10. 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....

  11. Graft rejection after hematopoietic cell transplantation with nonmyeloablative conditioning.

    Science.gov (United States)

    Masmas, Tania N; Petersen, Søren L; Madsen, Hans O; Ryder, Lars P; Kornblit, Brian; Svejgaard, Arne; Andersen, Pernille; Dickmeiss, Ebbe; Vindeløv, Lars L

    2008-07-01

    Graft rejection after hematopoietic cell transplantation (HCT) with nonmyeloablative conditioning is a rare but serious clinical problem. Graft rejection and salvage therapy in eight patients in a retrospective analysis of 124 consecutive patients is reported. The patients were conditioned with low-dose fludarabine and total body irradiation (TBI). The association of pretransplantation risk factors with rejection and the effect of chimerism and graft-versus-host disease on rejection were analyzed. Overall survival (OS) and progression free survival (PFS) were compared between patients with and without rejection. Retransplantation was performed with increased TBI conditioning for all patients, and with increased mycophenolate mofetil doses for recipients with HLA-identical sibling donors. No known pretransplantation risk factors were confirmed in this study. Rejection episodes were unevenly distributed over time. The storage temperature of the apheresis products was identified as a risk factor for rejection. Storage of the apheresis products at 5 degrees C diminished the risk of rejection. Low donor T cell chimerism at Day +14 significantly increased the risk of rejection. Seven patients were retransplanted. All but one engrafted successfully, but with decreased OS and PFS. Two patients received pentostatin infusion prior to donor lymphocyte infusions in unsuccessful attempts at reversing rejection. Storage temperature and donor chimerism had a significant effect on rejection. Following rejection, patients are at greater risk of dying from infections and progression/relapse of their malignancy. Retransplantation is feasible and well tolerated after HCT with nonmyeloablative conditioning and should be performed without delay in patients with imminent and manifest graft rejection. PMID:18383319

  12. Our Experience with Autologous Bone Marrow Stem Cell Application in Dilated Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Mukund K

    2009-01-01

    Full Text Available Background - Use of autologous bone marrow stem cell is a newly evolving treatment modality for end stage cardiac failure as reported in the literature. We report our experience with two patients with dilated cardiomyopathy who underwent this treatment after failure of maximal conventional therapy. Methods - A 29 year old Male patient with history of orthopnea and PND, with a diagnosis of dilated cardiomyopathy and echocardiographic evidence of severe LV dysfunction was referred for further treatment. His echo on admission showed EF of 17% and no other abnormal findings except elevated bilirubin levels. He was in NYHA functional class IV. He received intracoronary injection of autologous bone marrow stem cells in January 2009. 254X106 cells were injected with a CD34+ of 0.20%. His clinical condition stabilized and he was discharged home. He received a second injection of 22X106 in vitro expanded stem cells with a CD34+ of 0.72% in Aug 2009. He is now in NYHA class II-III with EF 24%. A 31year old Male patient with history of increasing shortness of breath, severe over the past 3-4 days was admitted for evaluation and treatment. His echo on admission showed EF of 20% and was in NYHA functional class IV. Coronary angiogram was normal and he was stabilized on maximal anti failure measures. He received intracoronary autologous bone marrow stem cell injection of 56X106 with a CD34+ of 0.53% in August 2009. His clinical condition stabilized over the next 10 days and he was discharged home. Conclusions - In our experience of two cases of dilated cardiomyopathy, safety of intracoronary injection of autologous bone marrow stem cells both isolated and in vitro expanded has been proven in both the cases with efficacy proven in one of the cases. Long term follow-up of these two cases and inclusion of more number of similar cases where all available conventional therapies have not resulted in significant improvement for such studies are planned.

  13. [Outcomes of using autologous peripheral-blood stem cells in patients with chronic lower arterial insufficiency].

    Science.gov (United States)

    Maksimov, A V; Kiiasov, A P; Plotnikov, M V; Maianskaia, S D; Shamsutdinova, I I; Gazizov, I M; Mavlikeev, M O

    2011-01-01

    Presented herein are the outcomes of using autologous peripheral blood stem cells (SCs) in patients with stage II В lower limb chronic obliterating diseases (according to A.V. Pokrovsky's classification). Autologous SCs had previously been stimulated by means of the recombinant granulocytic colony stimulating factor (G-CSF) for five days. On day six, we performed mobilization of the peripheral blood stem cells on the MSC+ unit by means of leukopheresis followed by intramuscular administration of half of the obtained dose into the affected extremity. The mean number of the transplanted mononuclears amounted to 6.73 ± 2.2 x 10(9) cells, with the number of CD34+ cells averaging 2.94 ± 2.312 x 10(7). Assessing the therapeutic outcomes at 3 and 6 months of follow-up showed a statistically significant increase in the ankle-brachial pressure index (ABPI) [being at baseline 0.59 ± 0.04, at 3 months - 0.66 ± 0.04 (P=0.001), and after 6 months - 0.73 ± .08 (P=0.035)], accompanied and followed by improved measures of the treadmill test, with the pain-free walking distance at baseline equalling 102.2 ± 11.55 m, after 3 months - 129 ± 11.13 m (P<0.001), and after 6 months - 140 ± 13.11 m=0.021 vs baseline). The findings of the immunohistochemical study confirmed the development of neoangiogenesis in the skeletal muscle and a 25 percent increase in the capillary-network density following administration of autologous stem cells into the muscle. The method of transplanting peripheral-blood autologous stem cells for treatment of patients presenting with distal forms of chronic obliterating insufficiency of the lower limbs proved safe and efficient. The findings obtained during this study made it possible to recommend extending the indications for its application at the expense of patients with critical ischaemia. PMID:21983456

  14. Pyrimidoindole derivatives are agonists of human hematopoietic stem cell self-renewal

    Science.gov (United States)

    Fares, Iman; Chagraoui, Jalila; Gareau, Yves; Gingras, Stéphane; Ruel, Réjean; Mayotte, Nadine; Csaszar, Elizabeth; Knapp, David J. H. F.; Miller, Paul; Ngom, Mor; Imren, Suzan; Roy, Denis-Claude; Watts, Kori L.; Kiem, Hans-Peter; Herrington, Robert; Iscove, Norman N.; Humphries, R. Keith; Eaves, Connie J.; Cohen, Sandra; Marinier, Anne; Zandstra, Peter W.; Sauvageau, Guy

    2015-01-01

    The small number of hematopoietic stem and progenitor cells in cord blood units limits their widespread use in human transplant protocols. We identified a family of chemically related small molecules that stimulates the expansion ex vivo of human cord blood cells capable of reconstituting human hematopoiesis for at least 6 months in immunocompromised mice. The potent activity of these newly identified compounds, UM171 being the prototype, is independent of suppression of the aryl hydrocarbon receptor, which targets cells with more-limited regenerative potential. The properties of UM171 make it a potential candidate for hematopoietic stem cell transplantation and gene therapy. PMID:25237102

  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. Identification of a novel population of human cord blood cells with hematopoietic and chondrocytic potential

    Institute of Scientific and Technical Information of China (English)

    Karen E JAY; Anne ROULEAU; T Michael UNDERHILL; Mickie BHATIA

    2004-01-01

    With the exception of mature erythrocytes, cells within the human hematopoietic system are characterized by the cell surface expression of the pan-leukocyte receptor CD45. Here, we identify a novel subset among mononuclear cord blood cells depleted of lineage commitment markers (Lin-) that are devoid of CD45 expression. Surprisingly, functional examination of Lin-CD45- cells also lacking cell surface CD34 revealed they were capable of multipotential hematopoietic progenitor capacity. Co-culture with mouse embryonic limb bud cells demonstrated that Lin-CD45-CD34- cells were capable of contributing to cartilage nodules and differentiating into human chondrocytes. BMP-4, a mesodermal factor known to promote chondrogenesis, significantly augmented Lin-CD45-CD34- differentiation into chondrocytes.Moreover, unlike CD34+ human hematopoietic stem cells, Lin-CD45-CD34- cells were unable to proliferate or survive in liquid cultures, whereas single Lin-CD45-CD34- cells were able to chimerize the inner cell mass (ICM) of murine blastocysts and proliferate in this embryonic environment. Our study identifies a novel population of Lin-CD45-CD34-cells capable of commitment into both hematopoietic and chondrocytic lineages, suggesting that human cord blood may provide a more ubiquitous source of tissue with broader developmental potential than previously appreciated.

  17. The combination of valproic acid and lithium delays hematopoietic stem/progenitor cell differentiation.

    NARCIS (Netherlands)

    Walasek, M.A.; Bystrykh, L.; Boom, V. van den; Olthof, S.; Ausema, A.; Ritsema, M.; Huls, G.A.; Haan, G. de; Os, R. van

    2012-01-01

    Despite increasing knowledge on the regulation of hematopoietic stem/progenitor cell (HSPC) self-renewal and differentiation, in vitro control of stem cell fate decisions has been difficult. The ability to inhibit HSPC commitment in culture may be of benefit to cell therapy protocols. Small molecule

  18. Nucleofection, an efficient nonviral method to transfer genes into human hematopoietic stem and progenitor cells.

    NARCIS (Netherlands)

    Levetzow, G. von; Spanholtz, J.; Beckmann, J.; Fischer, J.; Kogler, G.; Wernet, P.; Punzel, M.; Giebel, B.

    2006-01-01

    The targeted manipulation of the genetic program of single cells as well as of complete organisms has strongly enhanced our understanding of cellular and developmental processes and should also help to increase our knowledge of primary human stem cells, e.g., hematopoietic stem cells (HSCs), within

  19. GATA-3 regulates hematopoietic stem cell maintenance and cell-cycle entry

    OpenAIRE

    Ku, Chia-Jui; Hosoya, Tomonori; Maillard, Ivan; Engel, James Douglas

    2012-01-01

    Maintaining hematopoietic stem cell (HSC) quiescence is a critical property for the life-long generation of blood cells. Approximately 75% of cells in a highly enriched long-term repopulating HSC (LT-HSC) pool (Lin−Sca1+c-KithiCD150+CD48−) are quiescent, with only a small percentage of the LT-HSCs in cycle. Transcription factor GATA-3 is known to be vital for the development of T cells at multiple stages in the thymus and for Th2 differentiation in the peripheral organs. Although it is well d...

  20. The effects of proliferation and DNA damage on hematopoietic stem cell function determine aging.

    Science.gov (United States)

    Khurana, Satish

    2016-07-01

    In most of the mammalian tissues, homeostasis as well as injury repair depend upon a small number of resident adult stem cells. The decline in tissue/organ function in aged organisms has been directly linked with poorly functioning stem cells. Altered function of hematopoietic stem cells (HSCs) is at the center of an aging hematopoietic system, a tissue with high cellular turnover. Poorly engrafting, myeloid-biased HSCs with higher levels of DNA damage accumulation are the hallmark features of an aged hematopoietic system. These cells show a higher proliferation rate than their younger counterparts. It was proposed that quiescence of these cells over long period of time leads to accumulation of DNA damage, eventually resulting in poor function/pathological conditions in hematopoietic system. However, various mouse models with premature aging phenotype also show highly proliferative HSCs. This review examines the evidence that links proliferation of HSCs with aging, which leads to functional changes in the hematopoietic system. Developmental Dynamics 245:739-750, 2016. © 2016 Wiley Periodicals, Inc. PMID:26813236

  1. 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. PMID:27242795

  2. Correlation between survivin mRNA expression and homoharringtonine induced apoptosis of malignant hematopoietic cells

    Institute of Scientific and Technical Information of China (English)

    CAI Zhen; BAO Han-ying; LIN Mao-fang

    2005-01-01

    Background The inhibitor of apoptosis (IAP) gene family is involved in the suppression of apoptotic cell death as well as an increasing number of seemingly unrelated cellular functions. It is not known, however, whether IAP expression in malignant hematopoietic cells is affected by chemotherapeutic agents such as homoharringtonine (HHT). In this study, we investigated mRNA expression levels of IAPs, especially survivin, in various hematopoietic cell lines in relation with apoptosis induced by HHT. Methods Semiquantitative reverse transcriptase polymerase chain reaction was used to determine survivin mRNA levels. Cell apoptosis was examined by flow cytometry. Cell viability and proliferation assay was evaluated by MTT. The experiments were performed on the malignant hematopoietic cell lines MUTZ-1, K562, Jurkat, RMPI and HL60, with or without survivin antisense-oligodeoxynucleotides (AS-ODN) and HHT.Results The expression levels of survivin mRNA were variable in the cell lines and negatively correlated to HHT induced cell apoptosis. Survivin AS-ODN significantly decreased mRNA level of survivin, but not those of bax and bcl-2. Survivin also inhibited MUTZ-1 cell growth and induced apoptosis in a dose dependent manner. AS-ODN and HHT showed synergistic effect on MUTZ-1 cell growth.Conclusion The apoptotic effect of HHT on the hematopoietic cell lines is associated with decreased level of survivin expression. Survivin could be a new marker for drug sensitivity and a new target for cancer treatment.

  3. Expansive effects of aorta-gonad-mesonephros-derived stromal cells on hematopoietic stem cells from embryonic stem cells

    Institute of Scientific and Technical Information of China (English)

    FU Jin-rong; LIU Wen-li; ZHOU Yu-feng; ZHOU Jian-feng; SUN Han-ying; LUO Li; ZHANG Heng; XU Hui-zhen

    2005-01-01

    Background Hematopoietic stem cells (HSCs) give rise to all blood and immune cells and are used in clinical transplantation protocols to treat a wide variety of refractory diseases, but the amplification of HSCs has been difficult to achieve in vitro. In the present study, the expansive effects of aorta-gonad-mesonephros (AGM) region derived stromal cells on HSCs were explored, attempting to improve the efficiency of HSC transplantation in clinical practice.Methods The murine stromal cells were isolated from the AGM region of 12 days postcoitum (dpc) murine embryos and bone marrow(BM)of 6 weeks old mice, respectively. After identification with flow cytometry and immunocytochemistry, the stromal cells were co-cultured with ESCs-derived, cytokines-induced HSCs. The maintenance and expansion of ESCs-derived HSCs were evaluated by detecting the population of CD34+ and CD34+Sca-1+cells with flow cytometry and the blast colony-forming cells (BL-CFCs), high proliferative potential colony-forming cells (HPP-CFCs) by using semi-solid medium colonial culture. Finally, the homing and hematopoietic reconstruction abilities of HSCs were evaluated using a murine model of HSC transplantation in vivo.Results AGM and BM-derived stromal cells were morphologically and phenotypically similar, and had the features of stromal cells. When co-cultured with AGM or BM stromal cells, more primitive progenitor cells (HPP-CFCs ) could be detected in ESCs derived hematopoietic precursor cells, but BL-CFC's expansion could be detected only when co-cultured with AGM-derived stromal cells. The population of CD34+ hematopoietic stem/progenitor cells were expanded 3 times,but no significant expansion in the population of CD34+Sca-1+ cells was noted when co-cultured with BM stromal cells. While both CD34+ hematopoietic stem/progenitor cells and CD34+Sca-1+ cells were expanded 4 to 5 times respectively when co-cultured with AGM stromal cells. AGM region-derived stromal cells, like BM-derived stromal

  4. Canonical Wnt signaling promotes early hematopoietic progenitor formation and erythroid specification during embryonic stem cell differentiation.

    Directory of Open Access Journals (Sweden)

    Anuradha Tarafdar

    Full Text Available The generation of hematopoietic stem cells (HSCs during development is a complex process linked to morphogenic signals. Understanding this process is important for regenerative medicine applications that require in vitro production of HSC. In this study we investigated the effects of canonical Wnt/β-catenin signaling during early embryonic differentiation and hematopoietic specification using an embryonic stem cell system. Our data clearly demonstrates that following early differentiation induction, canonical Wnt signaling induces a strong mesodermal program whilst maintaining a degree of stemness potential. This involved a complex interplay between β-catenin/TCF/LEF/Brachyury/Nanog. β-catenin mediated up-regulation of TCF/LEF resulted in enhanced brachyury levels, which in-turn lead to Nanog up-regulation. During differentiation, active canonical Wnt signaling also up-regulated key transcription factors and cell specific markers essential for hematopoietic specification, in particular genes involved in establishing primitive erythropoiesis. This led to a significant increase in primitive erythroid colony formation. β-catenin signaling also augmented early hematopoietic and multipotent progenitor (MPP formation. Following culture in a MPP specific cytokine cocktail, activation of β-catenin suppressed differentiation of the early hematopoietic progenitor population, with cells displaying a higher replating capacity and a propensity to form megakaryocytic erythroid progenitors. This bias towards erythroid lineage commitment was also observed when hematopoietic progenitors were directed to undergo myeloid colony formation. Overall this study underscores the importance of canonical Wnt/β-catenin signaling in mesodermal specification, primitive erythropoiesis and early hematopietic progenitor formation during hematopoietic induction.

  5. 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.

  6. Placenta as a source of hematopoietic stem cells

    NARCIS (Netherlands)

    E.A. Dzierzak (Elaine); C. Robin (Catherine)

    2010-01-01

    textabstractThe placenta is a large, highly vascularised hematopoietic tissue that functions during the embryonic and foetal development of eutherian mammals. Although recognised as the interface tissue important in the exchange of oxygen, nutrients and waste products between the foetus and mother,

  7. Reengineering autologous bone grafts with the stem cell activator WNT3A.

    Science.gov (United States)

    Jing, Wei; Smith, Andrew A; Liu, Bo; Li, Jingtao; Hunter, Daniel J; Dhamdhere, Girija; Salmon, Benjamin; Jiang, Jie; Cheng, Du; Johnson, Chelsey A; Chen, Serafine; Lee, Katherine; Singh, Gurpreet; Helms, Jill A

    2015-04-01

    Autologous bone grafting represents the standard of care for treating bone defects but this biomaterial is unreliable in older patients. The efficacy of an autograft can be traced back to multipotent stem cells residing within the bone graft. Aging attenuates the viability and function of these stem cells, leading to inconsistent rates of bony union. We show that age-related changes in autograft efficacy are caused by a loss in endogenous Wnt signaling. Blocking this endogenous Wnt signal using Dkk1 abrogates autograft efficacy whereas providing a Wnt signal in the form of liposome-reconstituted WNT3A protein (L-WNT3A) restores bone forming potential to autografts from aged animals. The bioengineered autograft exhibits significantly better survival in the hosting site. Mesenchymal and skeletal stem cell populations in the autograft are activated by L-WNT3A and mitotic activity and osteogenic differentiation are significantly enhanced. In a spinal fusion model, aged autografts treated with L-WNT3A demonstrate superior bone forming capacity compared to the standard of care. Thus, a brief incubation in L-WNT3A reliably improves autologous bone grafting efficacy, which has the potential to significantly improve patient care in the elderly. PMID:25682158

  8. PRDM11 is dispensable for the maintenance and function of hematopoietic stem and progenitor cells

    DEFF Research Database (Denmark)

    Thoren, Lina A; Fog, Cathrine K; Jensen, Klaus T;

    2013-01-01

    Hematopoietic stem cells (HSC)(1) supply organisms with life-long output of mature blood cells. To do so, the HSC pool size has to be maintained by HSC self-renewing divisions. PRDM3 and PRDM16 have been documented to regulate HSC self-renewal, maintenance and function. We found Prdm11 to have...... similar expression patterns in the hematopoietic stem and progenitor cell (HSPC) compartments as Prdm3 and Prdm16. Therefore, we undertook experiments to test if PRDM11 regulates HSC self-renewal, maintenance and function by investigating the Prdm11(-/-) mice. Our data shows that phenotypic HSPCs...

  9. Potential of bursa-immigrated hematopoietic precursor cells to differentiate to functional B and T cells

    International Nuclear Information System (INIS)

    The potential of hematopoietic precursor cells, recently immigrated into the 13- and 14-day-old embryonic bursa, to migrate to the thymus and to differentiate to functional T cells was investigated. Chromosomally marked cell populations obtained from 13- and 14-day-old embryonic bursas were transferred i.v. to 780 R γ-irradiated chick embryos of equivalent age. When appropriate chimeras were examined at 4 to 12 weeks after cell transfer, donor cells were found to proliferate primarily in the bursa. Significant donor cell influx into the thymus was not detected. In correlation with these findings, Con A- and PHA-responsive T cells in thymus and spleen cell cultures of recipients remained of host origin whereas the number of anti-CIg responsive B cells of donor type increased gradually in the spleens of recipients. An initial lag period preceded the accumulation of functional donor B cells in the spleens of recipients, despite the predominant presence of dividing donor cells in the bursa. This suggests that the transferred bursal cell population required substantially longer to mature and emigrate from the bursa as functional B cells than the host cell population remaining in the irradiated bursas at time of cell transfer. The failure to detect significant influx of donor cells into the thymus and their failure to differentiate to functional T cells suggest that the recently bursa-immigrated hematopoietic stem cells of 13- and 14-day-old embryos may not be pluripotential cells, but rather cells already committed to the B cell line of differentiation

  10. Effect of genistein on cell cycle of bone marrow hematopoietic cells in normal and irradiated mice

    International Nuclear Information System (INIS)

    Objective: To study the effects of genistein on cell cycle, proliferation and expression of bcl-2 gene in bone marrow hematopoietic cells (BMHCs) of normal and irradiated mice in order to explore mechanisms for protection of genistein from radiation-induced hematopoietic system injury. Methods: Adult male BALB/c mice were orally administered with genistein (160 mg/kg b.w.) 24 h before irradiation. Cell cycles in BMHCs of the normal and irradiated mice were measured by flow cytometry. The protein and mRNA expressions of bcl-2 gene in BMHCs were analyzed by Western blot and RT-PCR, respectively. Results: a) Transitory and significant changes occurred in the cell cycle of BMHCs in the normal mice after administration of genistein: first, the proliferation suppression of BMHCs was observed and most cells were arrested in G0/G1 phase on day 1; second, progression of cells from G0/G1 phase into S phase was observed, accumulation of cells in S phase on day 2, and back to the normal level on day 4. b) Genistein, administration 24 h before irradiation, decreased the percentage of BMHCs in G0/G1 phase and increased cell proliferation. Moreover, genistein up-regulated the protein and mRNA expressions of bcl-2 in BMHCs in the irradiated mice. Conclusions: It was shown that changing with cell cycle, strengthening of radioresistant, suppressing of radiation-induced apoptosis, and enhancing of proliferation and differentiation of BMHCs maybe the underlying mechanisms for genistein protection of hematopoietic system against radiation damage. (authors)

  11. A novel potent Fas agonist for selective depletion of tumor cells in hematopoietic transplants

    OpenAIRE

    Nahimana, A; AUBRY, D.; Lagopoulos, L; Greaney, P.; Attinger, A; Demotz, S; Dawson, K. M.; Schapira, M; Tschopp, J; Dupuis, M.; Duchosal, M A

    2011-01-01

    There remains a clear need for effective tumor cell purging in autologous stem cell transplantation (ASCT) where residual malignant cells within the autograft contribute to disease relapse. Here we propose the use of a novel Fas agonist with potent pro-apoptotic activity, termed MegaFasL, as an effective ex-vivo purging agent. MegaFasL selectively kills hematological cancer cells from lymphomas and leukemias and prevents tumor development at concentrations that do not reduce the functional ca...

  12. Prostate cancer cells metastasize to the hematopoietic stem cell niche in bone

    Institute of Scientific and Technical Information of China (English)

    Evan T Keller

    2011-01-01

    @@ The majority of men with advanced prostate cancer develop bone metastases as opposed to metastases at other sites.1 It has been unclear why prostate cancer selectively metastasizes to and proliferates in bone.Recently, Shiozawa et al.Delineated a mechanism that may account for the establishment of prostate cancer in bone.2 Specifically, they identified that prostate cancer cells compete with hematopoietic stem cells (HSC) for the osteoblast in the HSC niche of the bone.Defining the mechanisms through which prostate cancer cells establish themselves in bone is critical towards developing effective therapeutic strategies to prevent or target bone metastases.

  13. Redefining endothelial progenitor cells via clonal analysis and hematopoietic stem/progenitor cell principals.

    Science.gov (United States)

    Yoder, Mervin C; Mead, Laura E; Prater, Daniel; Krier, Theresa R; Mroueh, Karim N; Li, Fang; Krasich, Rachel; Temm, Constance J; Prchal, Josef T; Ingram, David A

    2007-03-01

    The limited vessel-forming capacity of infused endothelial progenitor cells (EPCs) into patients with cardiovascular dysfunction may be related to a misunderstanding of the biologic potential of the cells. EPCs are generally identified by cell surface antigen expression or counting in a commercially available kit that identifies "endothelial cell colony-forming units" (CFU-ECs). However, the origin, proliferative potential, and differentiation capacity of CFU-ECs is controversial. In contrast, other EPCs with blood vessel-forming ability, termed endothelial colony-forming cells (ECFCs), have been isolated from human peripheral blood. We compared the function of CFU-ECs and ECFCs and determined that CFU-ECs are derived from the hematopoietic system using progenitor assays, and analysis of donor cells from polycythemia vera patients harboring a Janus kinase 2 V617F mutation in hematopoietic stem cell clones. Further, CFU-ECs possess myeloid progenitor cell activity, differentiate into phagocytic macrophages, and fail to form perfused vessels in vivo. In contrast, ECFCs are clonally distinct from CFU-ECs, display robust proliferative potential, and form perfused vessels in vivo. Thus, these studies establish that CFU-ECs are not EPCs and the role of these cells in angiogenesis must be re-examined prior to further clinical trials, whereas ECFCs may serve as a potential therapy for vascular regeneration. PMID:17053059

  14. Autologous bone marrow stem cell intralesional transplantation repairing bisphosphonate related osteonecrosis of the jaw

    Directory of Open Access Journals (Sweden)

    Cella Luigi

    2011-08-01

    Full Text Available Abstract Purpose Bisphosphonate - related osteonecrosis of the JAW (BRONJ is a well known side effect of bisphosphonate therapies in oncologic and non oncologic patients. Since to date no definitive consensus has been reached on the treatment of BRONJ, novel strategies for the prevention, risk reduction and treatment need to be developed. We report a 75 year old woman with stage 3 BRONJ secondary to alendronate and pamidronate treatment of osteoporosis. The patient was unresponsive to recommended treatment of the disease, and her BRONJ was worsening. Since bone marrow stem cells are know as being multipotent and exhibit the potential for differentiation into different cells/tissue lineages, including cartilage, bone and other tissue, we performed autologous bone marrow stem cell transplantation into the BRONJ lesion of the patient. Methods Under local anesthesia a volume of 75 ml of bone marrow were harvested from the posterior superior iliac crest by aspiration into heparinized siringes. The cell suspension was concentrated, using Ficoll - Hypaque® centrifugation procedures, in a final volume of 6 ml. Before the injection of stem cells into the osteonecrosis, the patient underwent surgical toilet, local anesthesia was done and spongostan was applied as a carrier of stem cells suspension in the bone cavity, then 4 ml of stem cells suspension and 1 ml of patient's activated platelet-rich plasma were injected in the lesion of BRONJ. Results A week later the residual spongostan was removed and two weeks later resolution of symptoms was obtained. Then the lesion improved with progressive superficialization of the mucosal layer and CT scan, performed 15 months later, shows improvement also of bone via concentric ossification: so complete healing of BRONJ (stage 0 was obtained in our patient, and 30 months later the patient is well and without signs of BRONJ. Conclusion To our knowledge this is the first case of BRONJ successfully treated with

  15. 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

    Science.gov (United States)

    Giralt, Sergio; Garderet, Laurent; Durie, Brian; Cook, Gordon; Gahrton, Gosta; Bruno, Benedetto; Hari, Paremesweran; Lokhorst, Henk; McCarthy, Phillip; Krishnan, Amrita; Sonneveld, Pieter; Goldschmidt, Harmut; Jagannath, Sundar; Barlogie, Bart; Mateos, Maria; Gimsing, Peter; Sezer, Orhan; Mikhael, Joseph; Lu, Jin; Dimopoulos, Meletios; Mazumder, Amitabha; Palumbo, Antonio; Abonour, Rafat; Anderson, Kenneth; Attal, Michel; Blade, Joan; Bird, Jenny; Cavo, Michele; Comenzo, Raymond; de la Rubia, Javier; Einsele, Hermann; Garcia-Sanz, Ramon; Hillengass, Jens; Holstein, Sarah; Johnsen, Hans Erik; Joshua, Douglas; Koehne, Guenther; Kumar, Shaji; Kyle, Robert; Leleu, Xavier; Lonial, Sagar; Ludwig, Heinz; Nahi, Hareth; Nooka, Anil; Orlowski, Robert; Rajkumar, Vincent; Reiman, Anthony; Richardson, Paul; Riva, Eloisa; Miguel, Jesus San; Turreson, Ingemar; Usmani, Saad; Vesole, David; Bensinger, William; Qazilbash, Muzaffer; Efebera, Yvonne; Mohty, Mohamed; Gasparreto, Christina; Gajewski, James; LeMaistre, Charles F.; Bredeson, Chris; Moreau, Phillipe; Pasquini, Marcelo; Kroeger, Nicolaus; Stadtmauer, Edward

    2016-01-01

    In 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 HCT has 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 a collaborative initiative to move the research agenda forward. After reviewing the available data, the expert committee came to the following consensus statement for salvage autologous HCT: (1) In transplantation-eligible patients relapsing after primary therapy that did NOT include an autologous HCT, high-dose therapy with HCT as part of salvage therapy should be considered standard; (2) High-dose therapy and autologous HCT should be considered appropriate therapy for any patients relapsing after primary therapy that includes an autologous HCT with initial remission duration of more than 18 months; (3) High-dose therapy and autologous HCT can be used as a bridging strategy to allogeneic HCT; (4) The role of postsalvage HCT maintenance needs to be explored in the context of well-designed prospective trials that should include new agents, such as monoclonal antibodies, immune-modulating agents, and oral proteasome inhibitors; (5) Autologous HCT consolidation should be explored as a strategy to develop novel conditioning regimens or post-HCT strategies in patients with short

  16. Financial Hardship and Patient-Reported Outcomes after Hematopoietic Cell Transplantation.

    Science.gov (United States)

    Abel, Gregory A; Albelda, Randy; Khera, Nandita; Hahn, Theresa; Salas Coronado, Diana Y; Odejide, Oreofe O; Bona, Kira; Tucker-Seeley, Reginald; Soiffer, Robert

    2016-08-01

    Although hematopoietic cell transplantation (HCT) is the only curative therapy for many advanced hematologic cancers, little is known about the financial hardship experienced by HCT patients nor the association of hardship with patient-reported outcomes. We mailed a 43-item survey to adult patients approximately 180 days after their first autologous or allogeneic HCT at 3 high-volume centers. We assessed decreases in household income; difficulty with HCT-related costs, such as need to relocate or travel; and 2 types of hardship: hardship_1 (reporting 1 or 2 of the following: dissatisfaction with present finances, difficulty meeting monthly bill payments, or not having enough money at the end of the month) and "hardship_2" (reporting all 3). Patient-reported stress was measured with the Perceived Stress Scale-4, and 7-point scales were provided for perceptions of overall quality of life (QOL) and health. In total, 325 of 499 surveys (65.1%) were received. The median days since HCT was 173; 47% underwent an allogeneic HCT, 60% were male, 51% were > 60 years old, and 92% were white. Overall, 46% reported income decline after HCT, 56% reported hardship_1, and 15% reported hardship_2. In multivariable models controlling for income, those reporting difficulty paying for HCT-related costs were more likely to report financial hardship (odds ratio, 6.9; 95% confidence interval, 3.8 to 12.3). Hardship_1 was associated with QOL below the median (odds ratio, 2.9; 95% confidence interval, 1.7 to 4.9), health status below the median (odds ratio, 2.2; 95% confidence interval, 1.3 to 3.6), and stress above the median (odds ratio, 2.1; 95% confidence interval, 1.3 to 3.5). In this sizable cohort of HCT patients, financial hardship was prevalent and associated with worse QOL and higher levels of perceived stress. Interventions to address patient financial hardship-especially those that ameliorate HCT-specific costs-are likely to improve patient-reported outcomes. PMID:27184627

  17. Coculture with hematopoietic stem cells protects cardiomyocytes against apoptosis via paracrine activation of AKT

    Directory of Open Access Journals (Sweden)

    Rosenberg Mark

    2012-06-01

    Full Text Available Abstract Background Previous experimental studies concluded that stem cells (SC may exert their beneficial effects on the ischemic heart by paracrine activation of antiapoptotic pathways. In order to identify potential cardioprotective mediators, we performed a systematic analysis of the differential gene expression of hematopoietic SC after coculture with cardiomyocytes (CM. Methods After 48 h of coculture with neonatal rat ventricular CM (NRVCM, two consecutive cell sorting steps generated a highly purified population of conditioned murine hematopoietic SC (>99%. Next, a genome-wide microarray analysis of cocultured vs. monocultured hematopoietic SC derived from three independent experiments was performed. The analysis of differentially expressed genes was focused on products that are secretable and/or membrane-bound and potentially involved in antiapoptotic signalling. Results We found CCL-12, Macrophage Inhibitory Factor, Fibronectin and connexin 40 significantly upregulated in our coculture model. An ELISA of cell culture supernatants was performed to confirm secretion of candidate genes and showed that coculture supernatants revealed markedly higher CCL-12 concentrations. Moreover, we stimulated NRVCM with concentrated coculture supernatants which resulted in a significant reduction of apoptosis compared to monoculture-derived supernatant. Mechanistically, NRVCMs stimulated with coculture supernatants showed a higher level of AKT-phosphorylation, consistent with enhanced antiapoptotic signaling. Conclusion In summary, our results show that the interaction between hematopoietic SC and NRVCM led to a modified gene expression and induction of antiapoptotic pathways. These findings may thus at least in part explain the cardioprotective effects of hematopoietic SC.

  18. The role of autologous haemopoietic stem cell transplantation in the treatment of autoimmune disorders.

    Science.gov (United States)

    Rebeiro, P; Moore, J

    2016-01-01

    Autologous haemopoietic stem cell transplantation (HSCT) has been used for over 30 years for malignant haematological diseases, such as myeloma and lymphoma, with considerable success. More recently this procedure has been adopted as a form of high dose immunosuppression in selected patients with autoimmune diseases that are resistant to conventional therapies. Animal models have previously outlined the rationale and validity of HSCT in patients with these non-malignant, but in many cases, life-threatening conditions. Recent data have that deletion of putative autoreactive immune clones with reconstitution of a thymic driven, tolerant immune system occurs in HSCT for auto-immune patients. Two randomised control trials have confirmed that HSCT is superior to monthly cyclophosphamide in systemic sclerosis with a highly significant disease free and overall survival benefit demonstrated in the Autologous Stem cell Transplantation International Scleroderma trial. Over 2000 patients worldwide with autoimmune conditions have been treated with HSCT - the commonest indications being multiple sclerosis (MS) and systemic sclerosis. Encouraging relapse free survival of 70-80% at 4 years, in heavily pre-treated MS patients, has been demonstrated in Phase II trials. A Phase III trial in MS patients who have failed interferon is currently accruing patients. Future challenges include improvements in safety of HSCT, particularly in cardiac assessment of systemic sclerosis patients, cost-benefit analyses of HSCT compared to standard therapy and establishment of centres of excellence to continue to enhance the safety and benefit of this exciting new therapy. PMID:26524106

  19. NMD is essential for hematopoietic stem and progenitor cells and for eliminating by-products of programmed DNA rearrangements

    DEFF Research Database (Denmark)

    Weischelfeldt, Joachim Lütken; Damgaard, Inge; Bryder, David;

    2008-01-01

    been addressed in detail. Here we use mouse genetics to demonstrate that hematopoietic-specific deletion of Upf2, a core NMD factor, led to the rapid, complete, and lasting cell-autonomous extinction of all hematopoietic stem and progenitor populations. In contrast, more differentiated cells were only...

  20. Hypercholesterolemia Tunes Hematopoietic Stem/Progenitor Cells for Inflammation and Atherosclerosis

    OpenAIRE

    Xiaojuan Ma; Yingmei Feng

    2016-01-01

    As the pathological basis of cardiovascular disease (CVD), atherosclerosis is featured as a chronic inflammation. Hypercholesterolemia is an independent risk factor for CVD. Accumulated studies have shown that hypercholesterolemia is associated with myeloid cell expansion, which stimulates innate and adaptive immune responses, strengthens inflammation, and accelerates atherosclerosis progression. Hematopoietic stem/progenitor cells (HSPC) in bone marrow (BM) expresses a panel of lipoprotein r...

  1. Control of AC133/CD133 and impact on human hematopoietic progenitor cells through nucleolin.

    Science.gov (United States)

    Bhatia, S; Reister, S; Mahotka, C; Meisel, R; Borkhardt, A; Grinstein, E

    2015-11-01

    AC133 is a prominent surface marker of CD34+ and CD34- hematopoietic stem/progenitor cell (HSPC) subsets. AC133+ HSPCs contain high progenitor cell activity and are capable of hematopoietic reconstitution. Furthermore, AC133 is used for prospective isolation of tumor-initiating cells in several hematological malignancies. Nucleolin is a multifunctional factor of growing and cancer cells, which is aberrantly active in certain hematological neoplasms, and serves as a candidate molecular target for cancer therapy. Nucleolin is involved in gene transcription and RNA metabolism and is prevalently expressed in HSPCs, as opposed to differentiated hematopoietic tissue. The present study dissects nucleolin-mediated activation of surface AC133 and its cognate gene CD133, via specific interaction of nucleolin with the tissue-dependent CD133 promoter P1, as a mechanism that crucially contributes to AC133 expression in CD34+ HSPCs. In mobilized peripheral blood (MPB)-derived HSPCs, nucleolin elevates colony-forming unit (CFU) frequencies and enriches granulocyte-macrophage CFUs. Furthermore, nucleolin amplifies long-term culture-initiating cells and also promotes long-term, cytokine-dependent maintenance of hematopoietic progenitor cells. Active β-catenin, active Akt and Bcl-2 levels in MPB-derived HSPCs are nucleolin-dependent, and effects of nucleolin on these cells partially rely on β-catenin activity. The study provides new insights into molecular network relevant to stem/progenitor cells in normal and malignant hematopoiesis. PMID:26183533

  2. The polycomb group gene Ezh2 prevents hematopoietic stem cell exhaustion

    NARCIS (Netherlands)

    Kamminga, LM; Bystrykh, LV; Boer, AC; Houwer, S; Douma, J; Weersing, E; Dontje, B; de Haan, G

    2006-01-01

    The molecular mechanism responsible for a decline of stem cell functioning after replicative stress remains unknown. We used mouse embryonic fibroblasts (MEFs) and hematopoietic stem cells (HSCs) to identify genes involved in the process of cellular aging. In proliferating and senescent MEFs one of

  3. A Rare Complication Developing After Hematopoietic Stem Cell Transplantation: Wernicke’s Encephalopathy

    Science.gov (United States)

    Solmaz, Soner; Gereklioğlu, Çiğdem; Tan, Meliha; Demir, Şenay; Yeral, Mahmut; Korur, Aslı; Boğa, Can; Özdoğu, Hakan

    2015-01-01

    Thiamine is a water-soluble vitamin. Thiamine deficiency can present as a central nervous system disorder known as Wernicke’s encephalopathy, which classically manifests as confusion, ataxia, and ophthalmoplegia. Wernicke’s encephalopathy has rarely been reported following hematopoietic stem cell transplantation. Herein, we report Wernicke’s encephalopathy in a patient with acute myeloid leukemia who had been receiving prolonged total parenteral nutrition after haploidentical allogeneic hematopoietic stem cell transplantation. To the best of our knowledge, this is the first case reported from Turkey in the literature. PMID:25912759

  4. A Rare Complication Developing After Hematopoietic Stem Cell Transplantation: Wernicke’s Encephalopathy

    Directory of Open Access Journals (Sweden)

    Soner Solmaz

    2015-12-01

    Full Text Available Thiamine is a water-soluble vitamin. Thiamine deficiency can present as a central nervous system disorder known as Wernicke’s encephalopathy, which classically manifests as confusion, ataxia, and ophthalmoplegia. Wernicke’s encephalopathy has rarely been reported following hematopoietic stem cell transplantation. Herein, we report Wernicke’s encephalopathy in a patient with acute myeloid leukemia who had been receiving prolonged total parenteral nutrition after haploidentical allogeneic hematopoietic stem cell transplantation. To the best of our knowledge, this is the first case reported from Turkey in the literature.

  5. An overlooked tumor promoting immunoregulation by non-hematopoietic stromal cells.

    Science.gov (United States)

    Bose, Anamika; Ghosh, Tithi; Baral, Rathindranath

    2016-08-01

    Multidirectional complex communication between tumor-residing hematopoietic and non-hematopoietic stromal cells (NHSCs) decisively regulates cancer development, progression and therapeutic responses. HSCs predominantly participate in the immune regulations, while, NHSCs, provide parenchymal support or serve as a conduit for other cells or support angiogenesis. However, recent reports suggest NHSCs can additionally participate in ongoing tumor promoting immune reactions within tumor-microenvironment (TME). In this review, based on the state-of-art knowledge and accumulated evidence by us, we discuss the role of quite a few NHSCs in tumor from immunological perspectives. Understanding such consequence of NHSCs will surely pave the way in crafting effective cancer management. PMID:27311851

  6. Tracking the elusive fibrocyte: identification and characterization of collagen-producing hematopoietic lineage cells during murine wound healing.

    Science.gov (United States)

    Suga, Hirotaka; Rennert, Robert C; Rodrigues, Melanie; Sorkin, Michael; Glotzbach, Jason P; Januszyk, Michael; Fujiwara, Toshihiro; Longaker, Michael T; Gurtner, Geoffrey C

    2014-05-01

    Fibrocytes are a unique population of circulating cells reported to exhibit characteristics of both hematopoietic and mesenchymal cells, and play an important role in wound healing. However, putative fibrocytes have been found to lose expression of hematopoietic surface markers such as CD45 during differentiation, making it difficult to track these cells in vivo with conventional methodologies. In this study, to distinguish hematopoietic and nonhematopoietic cells without surface markers, we took advantage of the gene vav 1, which is expressed solely on hematopoietic cells but not on other cell types, and established a novel transgenic mouse, in which hematopoietic cells are irreversibly labeled with green fluorescent protein and nonhematopoietic cells with red fluorescent protein. Use of single-cell transcriptional analysis in this mouse model revealed two discrete types of collagen I (Col I) expressing cells of hematopoietic lineage recruited into excisional skin wounds. We confirmed this finding on a protein level, with one subset of these Col I synthesizing cells being CD45+ and CD11b+, consistent with the traditional definition of a fibrocyte, while another was CD45- and Cd11b-, representing a previously unidentified population. Both cell types were found to initially peak, then reduce posthealing, consistent with a disappearance from the wound site and not a loss of identifying surface marker expression. Taken together, we have unambiguously identified two cells of hematopoietic origin that are recruited to the wound site and deposit collagen, definitively confirming the existence and natural time course of fibrocytes in cutaneous healing. PMID:24446236

  7. Circulating hematopoietic progenitors and CD34+ cells predicted successful hematopoietic stem cell harvest in myeloma and lymphoma patients: experiences from a single institution

    Directory of Open Access Journals (Sweden)

    Yu JT

    2016-02-01

    Full Text Available Jui-Ting Yu,1,2,* Shao-Bin Cheng,3,* Youngsen Yang,1 Kuang-Hsi Chang,4 Wen-Li Hwang,1 Chieh-Lin Jerry Teng,1,5,6 1Division of Hematology/Medical Oncology, Department of Medicine, Taichung Veterans General Hospital, 2Division of Hematology/Medical Oncology, Tungs' Taichung MetroHarbor Hospital, 3Division of General Surgery, Department of Surgery, 4Department of Medical Research and Education, Taichung Veterans General Hospital, 5Department of Life Science, Tunghai University, 6School of Medicine, Chung Shan Medical University, Taichung, Taiwan, Republic of China *These authors contributed equally to this work Background: Previous studies have shown that the numbers of both circulating hematopoietic progenitor cell (HPC and CD34+ cell are positively correlated with CD34+ cell harvest yield. However, the minimal numbers of both circulating HPCs and CD34+ cells required for performing an efficient hematopoietic stem cell (HSC harvest in lymphoma and myeloma patients have not been defined in our institution. Patients and methods: Medical records of 50 lymphoma and myeloma patients undergoing peripheral blood HSC harvest in our institution were retrospectively reviewed. The minimal and optimal HSC harvest yield required for the treatment was considered to be ≥2×106 CD34+ cells/kg and ≥5×106 CD34+ cells/kg, respectively. Results: The minimally required or optimal HSC yield obtained was not influenced by age (≥60 years, sex, underlying malignancies, disease status, multiple rounds of chemotherapy, or history of radiotherapy. The numbers of both circulating HPC and CD34+ cell were higher in patients with minimally required HSC yields (P=0.000 for HPC and P=0.000 for CD34+ cell and also in patients with optimal HSC yields (P=0.011 for HPC and P=0.006 for CD34+ cell. The cell count cutoff for obtaining minimally required HSC harvest was determined to be 20/mm3 for HPCs and 10/mm3 for CD34+ cells. Furthermore, the cell count cutoff for obtaining

  8. Real-time monitoring of hematopoietic cell interaction with fibronectin fragment

    OpenAIRE

    Obr, Adam; Röselová, Pavla; Grebeňová, Dana; Kuželová, Kateřina

    2013-01-01

    Real-time cell analysis (RTCA) system based on measurement of electrical microimpedance has been introduced to monitor adherent cell cultures. We describe its use for real-time analysis of hematopoietic cell adhesion to bone marrow stroma proteins. Cells growing in suspension do not generate any significant change in the microimpedance signal until the surface with embedded microelectrodes is coated with a cell-binding protein. We show that in this case, the microimpedance signal specifically...

  9. Basal Cell Skin Cancer after Total-Body Irradiation and Hematopoietic Cell Transplantation

    OpenAIRE

    Schwartz, Jeffrey L.; Kopecky, Kenneth J.; Robert W. Mathes; Leisenring, Wendy M; Friedman, Debra L.; Deeg, H. Joachim

    2009-01-01

    Previous studies identified radiation therapy as a key modifier of basal cell carcinoma (BCC) risk in survivors of hematopoietic cell transplantation (HCT). In the present analysis, risk of BCC was analyzed in relation to age at transplant, attained age, race, total-body irradiation (TBI), and radiation fractionation in 6,306 patients who received HCT at ages 0–65 years after conditioning regimens with (n = 3870) or without (n = 2436) TBI, and who were followed from 100 days to 36.2 years aft...

  10. Development of Hematopoietic and Endothelial Cells from Human Embryonic Stem Cells: Lessons from the Studies using Mouse as a Model

    OpenAIRE

    Anna Jezierski; Albert Swedani; Lisheng Wang

    2007-01-01

    The current progress using the human embryonic stem cell (hESC) model system has provided much insight into the early origins of the hematopoietic and endothelial lineages, particularly the elusive hemangioblast. Recently, the cellular hierarchy and molecular regulation controlling hematopoietic commitment have been further elucidated. These findings not only provide new insights into early human development, but also advance the knowledge required to develop techniques capable of generating ...

  11. Adoptive precursor cell therapy to enhance immune reconstitution after hematopoietic stem cell transplantation in mouse and man

    Science.gov (United States)

    Holland, Amanda M.; Zakrzewski, Johannes L.; Goldberg, Gabrielle L.; Ghosh, Arnab

    2016-01-01

    Hematopoietic stem cell transplantation is a curative therapy for hematological malignancies. T cell deficiency following transplantation is a major cause of morbidity and mortality. In this review, we discuss adoptive transfer of committed precursor cells to enhance T cell reconstitution and improve overall prognosis after transplantation. PMID:19015856

  12. Cardiac atrioventricular conduction improved by autologous transplantation of mesenchymal stem cells in canine atrioventricular block models

    Institute of Scientific and Technical Information of China (English)

    Xiaoqing Ren; Jielin Pu; Shu Zhang; Liang Meng; Fangzheng Wang

    2007-01-01

    Objective Atrioventricular block (AVB) is a common and serious arrhythmia. At present, there is no perfect method of treatment for this kind of arrhythmia. The purpose of this study was to regenerate cardiac atrioventricular conduction by autologous transplantation of bone marrow mesenchymal stem cells (MSCs), and explore new methods for therapy of atrioventricular block. Methods Eleven Mongrel canines were randomized to MSCs transplantation (n=6) or control (n=5) group. The models of permanent and complete AVB in 11 canines were established by ablating His bundle with radiofrequency technique. At 4 weeks after AVB, bone marrow was aspirated from the iliac crest. MSCs were isolated and culture-expanded by means of gradient centrifugal and adherence to growth technique, and differentiated by 5-azacytidine in vitro. Differentiated MSCs (1ml, 1.5×107cells) labeled with BrdU were autotransplanted into His bundle area of canines by direct injection in the experimental group, and 1ml DMEM in the control group. At 1-12 weeks after operation,the effects of autologous MSCs transplantation on AVB models were evaluated by electrocardiogram, pathologic and immunohistochemical staining technique. Results Compared with the control group, there was a distinct improvement in atrioventricular conduction function in the experimental group. MSCs transplanted in His bundle were differentiated into analogous conduction system cells and endothelial cells in vivo, and established gap junction with host cardiomyocytes. Conclusions The committed-induced MSCs transplanted into His bundle area could differentiate into analogous conduction system cells and improve His conduction function in canine AVB models.

  13. Flotillins are involved in the polarization of primitive and mature hematopoietic cells.

    Directory of Open Access Journals (Sweden)

    Lawrence Rajendran

    Full Text Available BACKGROUND: Migration of mature and immature leukocytes in response to chemokines is not only essential during inflammation and host defense, but also during development of the hematopoietic system. Many molecules implicated in migratory polarity show uniform cellular distribution under non-activated conditions, but acquire a polarized localization upon exposure to migratory cues. METHODOLOGY/PRINCIPAL FINDINGS: Here, we present evidence that raft-associated endocytic proteins (flotillins are pre-assembled in lymphoid, myeloid and primitive hematopoietic cells and accumulate in the uropod during migration. Furthermore, flotillins display a polarized distribution during immunological synapse formation. Employing the membrane lipid-order sensitive probe Laurdan, we show that flotillin accumulation in the immunological synapse is concomittant with membrane ordering in these regions. CONCLUSIONS: Together with the observation that flotillin polarization does not occur in other polarized cell types such as polarized epithelial cells, our results suggest a specific role for flotillins in hematopoietic cell polarization. Based on our results, we propose that in hematopoietic cells, flotillins provide intrinsic cues that govern segregation of certain microdomain-associated molecules during immune cell polarization.

  14. 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

  15. Lentivirus mediated HO-1 gene transfer enhances myogenic precursor cell survival after autologous transplantation in pig.

    Science.gov (United States)

    Laumonier, Thomas; Yang, Sheng; Konig, Stephane; Chauveau, Christine; Anegon, Ignacio; Hoffmeyer, Pierre; Menetrey, Jacques

    2008-02-01

    Cell therapy for Duchenne muscular dystrophy and other muscle diseases is limited by a massive early cell death following injections. In this study, we explored the potential benefit of heme oxygenase-1 (HO-1) expression in the survival of porcine myogenic precursor cells (MPCs) transplanted in pig skeletal muscle. Increased HO-1 expression was assessed either by transient hyperthermia or by HO-1 lentiviral infection. One day after the thermic shock, we observed a fourfold and a threefold increase in HSP70/72 and HO-1 levels, respectively. This treatment protected 30% of cells from staurosporine-induced apoptosis in vitro. When porcine MPC were heat-shocked prior to grafting, we improved cell survival by threefold at 5 days after autologous transplantation (26.3 +/- 5.5% surviving cells). After HO-1 lentiviral transduction, almost 60% of cells expressed the transgene and kept their myogenic properties to proliferate and fuse in vitro. Apoptosis of HO-1 transduced cells was reduced by 50% in vitro after staurosporine induction. Finally, a fivefold enhancement in cell survival was observed after transplantation of HO-1-group (47.5 +/- 9.1% surviving cells) as compared to the nls-LacZ-group or control group. These results identify HO-1 as a protective gene against early MPC death post-transplantation. PMID:18026170

  16. Involved field radiation therapy following high dose chemotherapy and autologous stem cell transplant benefits local control and survival in refractory or recurrent Hodgkin lymphoma

    International Nuclear Information System (INIS)

    Background and purpose: Patients with recurrent or primary refractory Hodgkin lymphoma (HL) treated with high dose chemotherapy (HDT) and autologous stem cell transplant (ASCT) commonly relapse post-ASCT in previous disease sites. We sought to evaluate involved field radiation therapy (IFRT) following ASCT and patterns of recurrence, overall survival (OS), and disease specific survival (DSS). Methods and materials: Between May 1993 and October 2003, 62 (n = 66) evaluable patients with refractory/relapsed HL underwent HDT followed by ASCT. Thirty-two (52%) patients received IFRT following transplant. Survival was calculated from the day of hematopoietic stem cell infusion. Results: Median follow-up was 2.3 years (range 0.03–11.56). Estimated 3-year OS (p = 0.05) and DSS (p = 0.08) were 69.6% and 82.1% with IFRT and 40% and 57.6% without IFRT on univariate analysis. B-symptoms were adverse on univariate (p = 0.007) and multivariate (p = 0.01) analysis. HL patients who received IFRT following ASCT had improved local control in areas of previously recurrent disease (p = 0.03). Conclusion: OS and DSS showed marginal benefit at 3 years. Given the retrospective nature of our study and attendant selection bias that can be both positive and negative, a future prospective study is warranted to better understand the value of IFRT in the transplant setting.

  17. Success of an International Learning Health Care System in Hematopoietic Cell Transplantation: The American Society of Blood and Marrow Transplantation Clinical Case Forum.

    Science.gov (United States)

    Barba, Pere; Burns, Linda J; Litzow, Mark R; Juckett, Mark B; Komanduri, Krishna V; Lee, Stephanie J; Devlin, Sean M; Costa, Luciano J; Khan, Shakila; King, Andrea; Klein, Andreas; Krishnan, Amrita; Malone, Adriana; Mir, Muhammad A; Moravec, Carina; Selby, George; Roy, Vivek; Cochran, Melissa; Stricherz, Melisa K; Westmoreland, Michael D; Perales, Miguel-Angel; Wood, William A

    2016-03-01

    The American Society for Blood and Marrow Transplantation (ASBMT) Clinical Case Forum (CCF) was launched in 2014 as an online secure tool to enhance interaction and communication among hematopoietic cell transplantation (HCT) professionals worldwide through the discussion of challenging clinical care issues. After 14 months, we reviewed clinical and demographical data of cases posted in the CCF from January 29, 2014 to March 18, 2015. A total of 137 cases were posted during the study period. Ninety-two cases (67%) were allogeneic HCT, 29 (21%) were autologous HCT, and in 16 (12%), the type of transplantation (autologous versus allogeneic) was still under consideration. The diseases most frequently discussed included non-Hodgkin lymphoma (NHL; n = 30, 22%), acute myeloid leukemia (n = 23, 17%), and multiple myeloma (MM; n = 20, 15%). When compared with the US transplantation activity reported by the US Department of Health and Human Services, NHL and acute lymphoblastic leukemia cases were over-represented in the CCF, whereas MM was under-represented (P community worldwide and may allow identification of areas of controversy or unmet need from clinical, educational and research perspectives. PMID:26718665

  18. Effects of expanded bone marrow cells supported by stromal cells on hematopoietic repair in lethally irradiated mice

    International Nuclear Information System (INIS)

    Objective: To compare the effects of bone marrow cells expanded under different conditions on hematopoietic repair of radiation injury. Methods: In the liquid expanded cultural system with several cytokines and/or a bone marrow stromal cell layer, bone marrow mononuclear cells of mice were expanded for 5 days. Then, the expanded cells were transplanted to lethally irradiated mice via the caudal vein. The hematopoietic recovery of mice after transplantation was assessed by analysing the peripheral blood Hb,WBC, TBC and observing the survival states. Results: Ex vivo expansion of bone marrow mononuclear cells with combined use of cytokines under our cultural conditions can not improve the hematopoietic recovery of post-irradiated mice, but the expansion supported by bone marrow stromal cells can accelerate this process significantly

  19. Autologous transplantation and management of younger patients with mantle cell lymphoma

    DEFF Research Database (Denmark)

    Geisler, Christian H

    2012-01-01

    -term disease control. The efficacy of CHOP as induction therapy before ASCT in MCL is questioned and there is now evidence that as pretreatment before ASCT, AraC + rituximab leads to deeper remission and prolongs progression-free survival compared to rituximab + CHOP. The treatment goal of complete clinical......Mantle cell lymphoma is traditionally conceived as one of the NHL subtypes with the worst prognosis and incurable. In responders to frontline induction with CHOP-like chemotherapy autologous stem cell transplantation (ASCT) is proven superior to interferon maintenance, but does not lead to long...... approach might lead to a shift of paradigm of MCL from an incurable to a curable lymphoma....

  20. Hematopoietic stem cell enhancer: a powerful tool in stem cell biology.

    Science.gov (United States)

    Koh, Cai Ping; Ng, Cherry Ee Lin; Nah, Giselle Sek Suan; Wang, Chelsia Qiuxia; Tergaonkar, Vinay; Matsumura, Takayoshi; Yokomizo, Tomomasa; Suda, Toshio; Osato, Motomi

    2015-06-01

    There has been considerable interest in identifying a cis-regulatory element that targets gene expression to stem cells. Such an element, termed stem cell enhancer, holds the promise of providing important insights into the transcriptional programs responsible for inherent stem cell-specific properties such as self-renewal capacity. The element also serves as a molecular handle for stem cell-specific marking, transgenesis and gene targeting, thereby becoming invaluable to stem cell research. A series of candidate enhancers have been identified for hematopoietic stem cells (HSCs). This review summarizes currently known HSC enhancers with emphasis on an intronic enhancer in the Runx1 gene which is essential for the generation and maintenance of HSCs. The element, named eR1 (+24m), is active specifically in HSCs, but not in progenitors, and is hence the most definitive HSC enhancer. PMID:25574754

  1. Lentivirus Vector Gene Expression during ES Cell-Derived Hematopoietic Development In Vitro

    OpenAIRE

    Hamaguchi, Isao; Woods, Niels-Bjarne; Panagopoulos, Ioannis; Andersson, Elisabet; Mikkola, Hanna; Fahlman, Cecilia; Zufferey, Romain; Carlsson, Leif; Trono, Didier; Karlsson, Stefan

    2000-01-01

    The murine embryonal stem (ES) cell virus (MESV) can express transgenes from the long terminal repeat (LTR) promoter/enhancer in undifferentiated ES cells, but expression is turned off upon differentiation to embryoid bodies (EBs) and hematopoietic cells in vitro. We examined whether a human immunodeficiency virus type 1-based lentivirus vector pseudotyped with the vesicular stomatitis virus G protein (VSV-G) could transduce ES cells efficiently and express the green fluorescent protein (GFP)...

  2. Infections Caused by Mycobacterium tuberculosis in Recipients of Hematopoietic Stem Cell Transplantation

    OpenAIRE

    KhalidAhmedAl-Anazi; ASMAMAL-JASSER; KhalidAlsaleh

    2014-01-01

    Mycobacterium tuberculosis (M. tuberculosis) infections are uncommon in recipients of hematopoietic stem cell transplantation. These infections are 10–40 times commoner in recipients of stem cell transplantation than in the general population but they are 10 times less in stem cell transplantation recipients compared to solid organ transplant recipients. The incidence of M. tuberculosis infections in recipients of allogeneic stem cell transplantation ranges between

  3. The Proapoptotic BH3-Only Protein Bim Is Expressed in Hematopoietic, Epithelial, Neuronal, and Germ Cells

    OpenAIRE

    O’Reilly, Lorraine A.; Cullen, Leonie; Visvader, Jane; Lindeman, Geoffrey J.; Print, Cris; Bath, Mary L.; Huang, David C. S.; Strasser, Andreas

    2000-01-01

    Proapoptotic Bcl-2 family members activate cell death by neutralizing their anti-apoptotic relatives, which in turn maintain cell viability by regulating the activation of the cell death effectors, the caspases. Bim belongs to a distinct subgroup of proapoptotic proteins that only resemble other Bcl-2 family members within the short BH3 domain. Gene targeting experiments in mice have shown that Bim is essential for the execution of some but not all apoptotic stimuli, for hematopoietic cell ho...

  4. Use of Autologous Mesenchymal Stem Cells Derived from Bone Marrow for the Treatment of Naturally Injured Spinal Cord in Dogs

    OpenAIRE

    Euler Moraes Penha; Cássio Santana Meira; Elisalva Teixeira Guimarães; Marcus Vinícius Pinheiro Mendonça; Faye Alice Gravely; Cláudia Maria Bahia Pinheiro; Taiana Maria Bahia Pinheiro; Stella Maria Barrouin-Melo; Ricardo Ribeiro-dos-Santos; Milena Botelho Pereira Soares

    2014-01-01

    The use of stem cells in injury repair has been extensively investigated. Here, we examined the therapeutic effects of autologous bone marrow mesenchymal stem cells (MSC) transplantation in four dogs with natural traumatic spinal cord injuries. MSC were cultured in vitro, and proliferation rate and cell viability were evaluated. Cell suspensions were prepared and surgically administered into the spinal cord. The animals were clinically evaluated and examined by nuclear magnetic resonance. Ten...

  5. Activated H-Ras regulates hematopoietic cell survival by modulating Survivin

    International Nuclear Information System (INIS)

    Survivin expression and Ras activation are regulated by hematopoietic growth factors. We investigated whether activated Ras could circumvent growth factor-regulated Survivin expression and if a Ras/Survivin axis mediates growth factor independent survival and proliferation in hematopoietic cells. Survivin expression is up-regulated by IL-3 in Ba/F3 and CD34+ cells and inhibited by the Ras inhibitor, farnesylthiosalicylic acid. Over-expression of constitutively activated H-Ras (CA-Ras) in Ba/F3 cells blocked down-modulation of Survivin expression, G0/G1 arrest, and apoptosis induced by IL-3 withdrawal, while dominant-negative (DN) H-Ras down-regulated Survivin. Survivin disruption by DN T34A Survivin blocked CA-Ras-induced IL-3-independent cell survival and proliferation; however, it did not affect CA-Ras-mediated enhancement of S-phase, indicating that the anti-apoptotic activity of CA-Ras is Survivin dependent while its S-phase enhancing effect is not. These results indicate that CA-Ras modulates Survivin expression independent of hematopoietic growth factors and that a CA-Ras/Survivin axis regulates survival and proliferation of transformed hematopoietic cells

  6. THE IMPROVEMENT OF INFARCTED MYOCARDIAL CONTRACTILE FORCE AFTER AUTOLOGOUS SKELETAL MUSCLE SATELLITE CELL IMPLANTATION

    Institute of Scientific and Technical Information of China (English)

    钟竑; 朱洪生; 张臻

    2002-01-01

    Objective To study the improvement of infarcted myocardial contractile force after autologous skeletal muscle satellite cell implantation via intracoronary arterial perfusion. Methods Skeletal muscle cells were harvested from gluteus max of adult mongrel dogs and the cells were cultured and expanded before being labeled with DAPI (4, 6-diamidino-2-phenylindone). The labeled cells were then implanted into the acute myocardial infarct site via the ligated left anterior descending (LAD) coronary artery. Specimens were taken at 2nd, 4th, 8th week after myoblast implantation for histologic and contractile force evaluation, respectively. Results The satellite cells with fluorescence had been observed in the infarct site and also in papi-llary muscle with consistent oriented direction of host myocardium. A portion of the implanted cells had differen-tiated into muscle fibers. Two weeks after implantation, the myocardial contractile force showed no significant difference between the cell implant group and control group. At 4 and 8 week, the contractile force in the cell implant group was better than that in control group. Conclusion The skeletal muscle satellite cells, implanted into infarct myocardium by intracoronary arterial perfusion, could disseminate through the entire infarcted zone with myocardial regeneration and improve the contractile function of the infarcted myocardium.

  7. Distinguishing autocrine and paracrine signals in hematopoietic stem cell culture using a biofunctional microcavity platform.

    Science.gov (United States)

    Müller, Eike; Wang, Weijia; Qiao, Wenlian; Bornhäuser, Martin; Zandstra, Peter W; Werner, Carsten; Pompe, Tilo

    2016-01-01

    Homeostasis of hematopoietic stem cells (HSC) in the mammalian bone marrow stem cell niche is regulated by signals of the local microenvironment. Besides juxtacrine, endocrine and metabolic cues, paracrine and autocrine signals are involved in controlling quiescence, proliferation and differentiation of HSC with strong implications on expansion and differentiation ex vivo as well as in vivo transplantation. Towards this aim, a cell culture analysis on a polymer microcavity carrier platform was combined with a partial least square analysis of a mechanistic model of cell proliferation. We could demonstrate the discrimination of specific autocrine and paracrine signals from soluble factors as stimulating and inhibitory effectors in hematopoietic stem and progenitor cell culture. From that we hypothesize autocrine signals to be predominantly involved in maintaining the quiescent state of HSC in single-cell niches and advocate our analysis platform as an unprecedented option for untangling convoluted signaling mechanisms in complex cell systems being it of juxtacrine, paracrine or autocrine origin. PMID:27535453

  8. Hematopoietic stem cells: ex-vivo expansion and therapeutic potential for myocardial ischemia

    Directory of Open Access Journals (Sweden)

    Jingwei Lu

    2010-03-01

    Full Text Available Jingwei Lu, Vincent J Pompili, Hiranmoy DasCardiovascular Stem Cell Research Laboratory, The Dorothy M Davis Heart and Lung Research Institute, The Ohio State University Medical Center, Columbus, OH 43210, USAAbstract: Despite recent advances in cardiovascular medicine, ischemic heart disease remains the major cause of death in the United States and abroad. Cell-based therapy for degenerative diseases like myocardial ischemia using stem cells is currently under serious investigation. Various types of stem cells are being considered to be candidates for cell transplantation in cell-based therapy. Hematopoietic stem cells are one of the most promising cell types as several studies demonstrated their ability to improve ischemic cardiac functions by enhancing neovascularization and by reducing the total size of scar tissue. However, in order to procure sufficient numbers of functional stem cells, ex-vivo expansion technology became critically important. In this review, we focus on the state-of-the-art ex-vivo technology for the expansion of hematopoietic stem cells, and the underlying mechanisms regulating stem cell self-renewal as well as differentiation.Keywords: ischemic heart disease, ex-vivo expansion, hematopoietic stem cells, cytokines, nanofibers

  9. Short intensive sequential therapy followed by autologous stem cell transplantation in adult Burkitt, Burkitt-like and lymphoblastic lymphoma

    NARCIS (Netherlands)

    G. van Imhoff (Gustaaf); B. van der Holt (Bronno); M.A. MacKenzie (Marius); G.J. Ossenkoppele (Gert); P.W. Wijermans (Pierre); M.H.H. Kramer (Mark); M.B. van 't Veer (Mars); H. Schouten (Harry); M. van Marwijk Kooy (Marinus); M.H.J. van Oers (Marinus); J. Raemaekers; P. Sonneveld (Pieter); L.A.M.H. Meulendijks (L. A M H); P.M. Kluin; H.C. Kluin-Nelemans (H.); L.F. Verdonck (Leo)

    2005-01-01

    textabstractThe feasibility and efficacy of up-front high-dose sequential chemotherapy followed by autologous stem cell transplantation (ASCT) in previously untreated adults (median age 33 years; range 15-64) with Burkitt lymphoma (BL), Burkitt-like lymphoma (BLL) or lymphoblastic lymphoma (LyLy), b

  10. Short intensive sequential therapy followed by autologous stem cell transplantation in adult Burkitt, Burkitt-like and lymphoblastic lymphoma

    NARCIS (Netherlands)

    van Imhoff, GW; van der Holt, B; MacKenzie, MA; Ossenkoppele, GJ; Wijermans, PW; Kramer, MHH; van't Veer, MB; Schouten, HC; Kooy, MV; van Oers, MHJ; Raemaekers, JMM; Sonneveld, P; Meulendijks, LAMH; Kluin, PM; Kluin-Nelemans, HC; Verdonck, LF

    2005-01-01

    The feasibility and efficacy of up- front high- dose sequential chemotherapy followed by autologous stem cell transplantation ( ASCT) in previously untreated adults ( median age 33 years; range 15 - 64) with Burkitt lymphoma ( BL), Burkitt- like lymphoma ( BLL) or lymphoblastic lymphoma ( LyLy), bot

  11. One enhancer mediates mafK transcriptional activation in both hematopoietic and cardiac muscle cells

    OpenAIRE

    Katsuoka, Fumiki; Motohashi, Hozumi; Onodera, Ko; Suwabe, Naruyoshi; Engel, James Douglas; Yamamoto, Masayuki

    2000-01-01

    Members of the small Maf family of transcription factors play important roles in hematopoiesis. Using transgenic assays, we discovered a tissue-specific enhancer 3′ to the mafK gene. This enhancer directs mafK transcription in hematopoietic as well as in developing cardiac muscle cells, and was thus designated the hematopoietic and cardiac enhancer of mafK (HCEK). Only two of four GATA consensus motifs identified within HCEK contributed to enhancer activity, and both of these sites were requi...

  12. Hematopoietic stem cell transplantation in thalassemia major and sickle cell disease: indications and management recommendations from an international expert panel

    Science.gov (United States)

    Angelucci, Emanuele; Matthes-Martin, Susanne; Baronciani, Donatella; Bernaudin, Françoise; Bonanomi, Sonia; Cappellini, Maria Domenica; Dalle, Jean-Hugues; Di Bartolomeo, Paolo; de Heredia, Cristina Díaz; Dickerhoff, Roswitha; Giardini, Claudio; Gluckman, Eliane; Hussein, Ayad Achmed; Kamani, Naynesh; Minkov, Milen; Locatelli, Franco; Rocha, Vanderson; Sedlacek, Petr; Smiers, Frans; Thuret, Isabelle; Yaniv, Isaac; Cavazzana, Marina; Peters, Christina

    2014-01-01

    Thalassemia major and sickle cell disease are the two most widely disseminated hereditary hemoglobinopathies in the world. The outlook for affected individuals has improved in recent years due to advances in medical management in the prevention and treatment of complications. However, hematopoietic stem cell transplantation is still the only available curative option. The use of hematopoietic stem cell transplantation has been increasing, and outcomes today have substantially improved compared with the past three decades. Current experience world-wide is that more than 90% of patients now survive hematopoietic stem cell transplantation and disease-free survival is around 80%. However, only a few controlled trials have been reported, and decisions on patient selection for hematopoietic stem cell transplantation and transplant management remain principally dependent on data from retrospective analyses and on the clinical experience of the transplant centers. This consensus document from the European Blood and Marrow Transplantation Inborn Error Working Party and the Paediatric Diseases Working Party aims to report new data and provide consensus-based recommendations on indications for hematopoietic stem cell transplantation and transplant management. PMID:24790059

  13. Effect of Remission Status and Induction Chemotherapy Regimen on Outcome of Autologous Stem Cell Transplantation for Mantle Cell Lymphoma

    OpenAIRE

    Till, Brian G.; Gooley, Theodore A.; Crawford, Nathan; Gopal, Ajay K.; Maloney, David G; Petersdorf, Stephen H.; Pagel, John M.; Holmberg, Leona; Bensinger, William; Press, Oliver W.

    2008-01-01

    We analyzed the outcomes of autologous stem cell transplantation (ASCT) following high-dose therapy with respect to remission status at the time of transplantation and induction regimen used in 56 consecutive patients with mantle cell lymphoma (MCL). Twenty-one patients received induction chemotherapy with HyperCVAD with or without rituximab (±R) followed by ASCT in first complete or partial remission (CR1/PR1), 15 received CHOP (±R) followed by ASCT in CR1/PR1, and 20 received ASCT following...

  14. Vaccination with autologous dendritic cells pulsed with multiple tumor antigens for treatment of patients with malignant melanoma: results from a phase I/II trial

    DEFF Research Database (Denmark)

    Trepiakas, Redas; Berntsen, Annika; Hadrup, Sine Reker;

    2010-01-01

    vaccination with autologous monocyte-derived mature dendritic cells (DC) pulsed with p53, survivin and telomerase-derived peptides (HLA-A2+ patients) or with autologous/allogeneic tumor lysate (HLA-A2(-) patients) in combination with low-dose interleukin (IL)-2 and interferon (IFN)-alpha2b....

  15. 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.

  16. Autologous Stem Cell Injection for Spinal Cord Injury - A Clinical Study from India.

    Directory of Open Access Journals (Sweden)

    Ravikumar R

    2007-01-01

    Full Text Available We studied 100 patients with Spinal Cord injury (SCI after Autologous Stem cell Injection in the Spinal fluid with a Follow up of 6 months post Stem cell injection. There were 69 males and 31 females; age ranging from 8 years to 55 years.? Time after Spinal Injury ranged from 11 years - 3 months (Average: 4.5 years. The Level of Injury ranged from Upper Thoracic (T1-T7 - 34 pts, Lower thoracic (T7-T12 -45 pts, Lumbar -12, Cervical-9 pts. All patients had an MRI Scan, urodynamic study and SSEP (somatosensory Evoked Potential tests before and 3 months after Stem cell Injection.80% of patients had Grade 0 power in the Lower limbs and rest had grade 1-2 power before stem cell injections. 70% of cases had complete lack of Bladder control and 95% had reduced detrusor function.We Extracted CD34 and CD 133 marked Stem cells from 100 ml of Bone marrow Aspirate using Ficoll Gradient method with Cell counting done using flowcytometry.15 ml of the Stem cell concentrate was injected into the Lumbar spinal fluid in aseptic conditions. The CD 34/CD45 counts ranged from 120-400 million cells in the total volume.6 months after Injection, 8 patients had more than 2 grades of Motor power improvement, 3 are able to walk with support. 1 patient with T12/L1 injury was able to walk without support. 12 had sensory tactile and Pain perception improvement and 8 had objective improvement in bladder control and Bladder Muscle contractility. A total of 18 patients had reported or observed improvement in Neurological status. 85% of patients who had motor Improvement had Lesions below T8. MRI, SSEP and Urodynamic Study data are gathered at regular intervals. Conclusion: This study shows that Quantitative and qualitative Improvement in the Neurological status of paralyzed patients after Spinal cord injury is possible after autologous bone marrow Stem cell Injections in select patients. There was no report of Allodynia indicating the safety of the procedure. Further studies to

  17. Autologous Bone Marrow Mononuclear Cell Transplantation Delays Progression of Carotid Atherosclerosis in Rabbits.

    Science.gov (United States)

    Cui, Kefei; Ma, Xiao; Yu, Lie; Jiang, Chao; Fu, Chao; Fu, Xiaojie; Yu, Xiaofang; Huang, Yuanjing; Hou, Suyun; Si, Caifeng; Chen, Zhengguang; Yu, Jing; Wan, Jieru; Wang, Jian

    2016-09-01

    Bone marrow mononuclear cells (BMMNCs) can counteract oxidative stress and inhibit the inflammatory response in focal ischemic stroke models. However, the effect of BMMNC transplantation on carotid atherosclerosis needs to be determined. The carotid atherosclerotic plaque model was established in New Zealand White rabbits by balloon injury and 8 weeks of high-fat diet. Rabbits were randomized to receive an intravenous injection of autologous bromodeoxyuridine (BrdU)-labeled BMMNCs or an equal volume of phosphate-buffered saline. Plaques were evaluated for expression of proinflammatory and anti-inflammatory cytokines, anti-oxidant proteins, and markers of cell death. BMMNCs migrated into atherosclerotic plaque on the first day after cell transplantation. BMMNC-treated rabbits had smaller plaques and more collagen deposition than did the vehicle-treated controls on day 28 (p < 0.05). BMMNC treatment significantly increased endothelial nitric oxide synthase and the anti-oxidant enzymes glutathione peroxidase and superoxide dismutase in plaques compared to vehicle treatment on day 7. BMMNC-treated rabbits also had lower levels of cleaved caspase-3 expression; lower levels of proinflammatory cytokines interleukin-1β, tumor necrosis factor alpha, and matrix metalloproteinase 9; and higher levels of insulin-like growth factor-1 and its receptor (p < 0.05). Autologous BMMNC transplantation can suppress the process of atherosclerotic plaque formation and is associated with enhanced anti-oxidative effect, reduced levels of inflammatory cytokines and cleaved caspase-3, and increased expression of insulin-like growth factor-1 and its receptor. BMMNC transplantation represents a novel approach for the treatment of carotid atherosclerosis. PMID:26232064

  18. IL-18 single nucleotide polymorphisms in hematologic malignancies with HLA matched sibling donor allogeneic hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    蔡小矜

    2014-01-01

    Objective To explore the impact of interleukin-18(IL-18)single nucleotide polymorphisms on outcomes of hematologic malignancies with HLA-matched sibling donor hematopoietic stem cell transplantation(allo-HSCT).Methods Single-nucleotide polymorphisms in IL-18 promoter was detected by PCR-sequence-specific primer analysis(PCR-SSP)in 93 recipients and their HLA matched sibling donors.Hematopoietic reconstitution,

  19. Outcome of hematopoietic stem cell transplantation for adenosine deaminase-deficient severe combined immunodeficiency

    NARCIS (Netherlands)

    Hassan, Amel; Booth, Claire; Brightwell, Alex; Allwood, Zoe; Veys, Paul; Rao, Kanchan; Hoenig, Manfred; Friedrich, Wilhelm; Gennery, Andrew; Slatter, Mary; Bredius, Robbert; Finocchi, Andrea; Cancrini, Caterina; Aiuti, Alessandro; Porta, Fulvio; Lanfranchi, Arnalda; Ridella, Michela; Steward, Colin; Filipovich, Alexandra; Marsh, Rebecca; Bordon, Victoria; Al-Muhsen, Saleh; Al-Mousa, Hamoud; Alsum, Zobaida; Al-Dhekri, Hasan; Al Ghonaium, Abdulaziz; Speckmann, Carsten; Fischer, Alain; Mahlaoui, Nizar; Nichols, Kim E.; Grunebaum, Eyal; Al Zahrani, Daifulah; Roifman, Chaim M.; Boelens, Jaap; Davies, E. Graham; Cavazzana-Calvo, Marina; Notarangelo, Luigi; Gaspar, H. Bobby

    2012-01-01

    Deficiency of the purine salvage enzyme adenosine deaminase leads to SCID (ADA-SCID). Hematopoietic cell transplantation (HCT) can lead to a permanent cure of SCID; however, little data are available on outcome of HCT for ADA-SCID in particular. In this multicenter retrospective study, we analyzed o

  20. Collapse of Telomere Homeostasis in Hematopoietic Cells Caused by Heterozygous Mutations in Telomerase Genes

    NARCIS (Netherlands)

    Aubert, Geraldine; Baerlocher, Gabriela M.; Vulto, Irma; Poon, Steven S.; Lansdorp, Peter M.

    2012-01-01

    Telomerase activity is readily detectable in extracts from human hematopoietic stem and progenitor cells, but appears unable to maintain telomere length with proliferation in vitro and with age in vivo. We performed a detailed study of the telomere length by flow FISH analysis in leukocytes from 835

  1. 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

  2. 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

  3. The Hematopoietic Stem and Progenitor Cell Cistrome: GATA Factor-Dependent cis-Regulatory Mechanisms.

    Science.gov (United States)

    Hewitt, K J; Johnson, K D; Gao, X; Keles, S; Bresnick, E H

    2016-01-01

    Transcriptional regulators mediate the genesis and function of the hematopoietic system by binding complex ensembles of cis-regulatory elements to establish genetic networks. While thousands to millions of any given cis-element resides in a genome, how transcriptional regulators select these sites and how site attributes dictate functional output is not well understood. An instructive system to address this problem involves the GATA family of transcription factors that control vital developmental and physiological processes and are linked to multiple human pathologies. Although GATA factors bind DNA motifs harboring the sequence GATA, only a very small subset of these abundant motifs are occupied in genomes. Mechanistic studies revealed a unique configuration of a GATA factor-regulated cis-element consisting of an E-box and a downstream GATA motif separated by a short DNA spacer. GATA-1- or GATA-2-containing multiprotein complexes at these composite elements control transcription of genes critical for hematopoietic stem cell emergence in the mammalian embryo, hematopoietic progenitor cell regulation, and erythroid cell maturation. Other constituents of the complex include the basic helix-loop-loop transcription factor Scl/TAL1, its heterodimeric partner E2A, and the Lim domain proteins LMO2 and LDB1. This chapter reviews the structure/function of E-box-GATA composite cis-elements, which collectively constitute an important sector of the hematopoietic stem and progenitor cell cistrome. PMID:27137654

  4. Long-term outcome of Hurler syndrome patients after hematopoietic cell transplantation : an international multicenter study

    NARCIS (Netherlands)

    Aldenhoven, Mieke; Wynn, Robert F.; Orchard, Paul J.; O'Meara, Anne; Veys, Paul; Fischer, Alain; Valayannopoulos, Vassili; Neven, Benedicte; Rovelli, Attilio; Prasad, Vinod K.; Tolar, Jakub; Allewelt, Heather; Jones, Simon A.; Parini, Rossella; Renard, Marleen; Bordon, Victoria; Wulffraat, Nico M.; de Koning, Tom J.; Shapiro, Elsa G.; Kurtzberg, Joanne; Boelens, Jaap Jan

    2015-01-01

    Mucopolysaccharidosis type I-Hurler syndrome (MPS-IH) is a lysosomal storage disease characterized by multisystem morbidity and death in early childhood. Although hematopoietic cell transplantation (HCT) has been performed in these patients for more than 30 years, large studies on the long-term outc

  5. Long-term outcome of Hurler syndrome patients after hematopoietic cell transplantation : An international multicenter study

    NARCIS (Netherlands)

    Aldenhoven, Mieke; Wynn, Robert F.; Orchard, Paul J.; O'Meara, Anne; Veys, Paul; Fischer, Alain; Valayannopoulos, Vassili; Neven, Benedicte; Rovelli, Attilio; Prasad, Vinod K.; Tolar, Jakub; Allewelt, Heather; Jones, Simon A.; Parini, Rossella; Renard, Marleen; Bordon, Victoria; Wulffraat, Nico M.; de Koning, Tom J.; Shapiro, Elsa G.; Kurtzberg, Joanne; Boelens, Jaap Jan

    2015-01-01

    Mucopolysaccharidosis type I-Hurler syndrome (MPS-IH) is a lysosomal storage disease characterized by multisystem morbidity and death in early childhood. Although hematopoietic cell transplantation (HCT) has been performed in these patients for more than 30 years, large studies on the long-term outc

  6. Pulmonary Rehabilitation for Bronchiolitis Obliterans Syndrome after Hematopoietic Stem Cell Transplantation

    OpenAIRE

    Tran, Jerry; Norder, Emily; Diaz, Phil; Gary S Phillips; Elder, Pat; Devine, Steven M; Wood, Karen L.

    2012-01-01

    Bronchiolitis obliterans syndrome (BOS) is a progressive, insidious lung disease affecting allogeneic hematopoietic stem cell transplant (HSCT) recipients. Unfortunately, there is no standardized approach for treatment of BOS in post HSCT patients. Pulmonary rehabilitation is a standard treatment in emphysema, an irreversible obstructive lung disease secondary to tobacco abuse. The National Emphysema Treatment Trial (NETT) demonstrated improved exercise tolerance, decrease dyspnea, and increa...

  7. Routine Surveillance for Bloodstream Infections in a Pediatric Hematopoietic Stem Cell Transplant Cohort: Do Patients Benefit?

    Directory of Open Access Journals (Sweden)

    Heather Rigby

    2007-01-01

    Full Text Available BACKGROUND: Hematopoietic stem cell transplant (HSCT recipients are at a high risk for late bloodstream infection (BSI. Controversy exists regarding the benefit of surveillance blood cultures in this immunosuppressed population. Despite the common use of this practice, the practical value is not well established in non-neutropenic children following HSCT.

  8. Graft-versus-host disease and graft-versus-tumor effects after allogeneic hematopoietic cell transplantation

    DEFF Research Database (Denmark)

    Storb, Rainer; Gyurkocza, Boglarka; Storer, Barry E;

    2013-01-01

    We designed a minimal-intensity conditioning regimen for allogeneic hematopoietic cell transplantation (HCT) in patients with advanced hematologic malignancies unable to tolerate high-intensity regimens because of age, serious comorbidities, or previous high-dose HCT. The regimen allows the pures...

  9. ERG promotes the maintenance of hematopoietic stem cells by restricting their differentiation

    DEFF Research Database (Denmark)

    Knudsen, Kasper Jermiin; Rehn, Matilda Carolina; Hasemann, Marie Sigurd;

    2015-01-01

    The balance between self-renewal and differentiation is crucial for the maintenance of hematopoietic stem cells (HSCs). Whereas numerous gene regulatory factors have been shown to control HSC self-renewal or drive their differentiation, we have relatively few insights into transcription factors...

  10. Engraftment potential of human fetal hematopoietic cells in NOD/SCID mice is not restricted to mitotically quiescent cells.

    Science.gov (United States)

    Wilpshaar, Jannine; Bhatia, Mickie; Kanhai, Humphrey H H; Breese, Robert; Heilman, Doug K; Johnson, Cynthia S; Falkenburg, J H Frederik; Srour, Edward F

    2002-07-01

    During fetal development, there is a continued demand for large numbers of primitive and mature hematopoietic cells. This demand may require that all potential hematopoietic stem cells (HSCs) migrate effectively to emerging hematopoietic sites and subsequently contribute to blood cell production, regardless of their cell cycle status. We recently established that umbilical cord blood cells in the G(1) phase of the cell cycle have a repopulating potential similar to cells in G(0), suggesting that cycling prenatal and neonatal HSCs may have the same functional capabilities described for quiescent, but not cycling, cells from adult sources. To establish the relationship between cell cycle status and hematopoietic potential at early stages of human ontogeny, the in vivo engraftment potential of mitotically defined fetal liver (FL) and fetal bone marrow (FBM) cells were examined in NOD/SCID recipients. Following transplantation of the same numbers of G(0), G(1), or S/G(2)+M CD34(+) cells from FL, equivalent percentages of recipient mice were chimeric (55%, 60%, and 60%, respectively). FBM-derived CD34(+) cells in all phases of the cell cycle engrafted in conditioned recipients and sustained human hematopoiesis, albeit at lower levels than their FL-derived counterparts. Multilineage differentiation was evident in all transplanted mice independent of the source or cell cycle status of graft cells. In addition, levels of chimerism in mice transplanted with fetal blood-derived G(0) or G(1) CD34(+) lineage-depleted cells were similar. These results support the assertion that mitotically quiescent and cycling fetal hematopoietic cells contain marrow-repopulating stem cells capable of multilineage engraftment in NOD/SCID mouse recipients. PMID:12070016

  11. TGFβ inhibition enhances the generation of hematopoietic progenitors from human ES cell-derived hemogenic endothelial cells using a stepwise strategy

    Institute of Scientific and Technical Information of China (English)

    Chengyan Wang; Liying Du; Yang Gao; Ming Yin; Mingxiao Ding; Hongkui Deng; Xuming Tang; Xiaomeng Sun; Zhenchuan Miao; Yaxin Lv; Yanlei Yang; Huidan Zhang; Pengbo Zhang; Yang Liu

    2012-01-01

    Embryonic hematopoiesis is a complex process.Elucidating the mechanism regulating hematopoietic differentiation from pluripotent stem cells would allow us to establish a strategy to efficiently generate hematopoietic cells.However,the mechanism governing the generation of hematopoietic progenitors from human embryonic stem cells (hESCs)remains unknown.Here,on the basis of the emergence of CD43+ hematopoietic cells from hemogenic endothelial (HE) cells,we demonstrated that VEGF was essential and sufficient,and that bFGF was synergistic with VEGF to specify the HE cells and the subsequent transition into CD43+ hematopoietic cells.Significantly,we identified TGFβ as a novel signal to regulate hematopoietic development,as the TGFβ inhibitor SB 431542 significantly promoted the transition from HE cells into CD43+ hematopoietic progenitor cells (HPCs) during hESC differentiation.By defining these critical signaling factors during hematopoietic differentiation,we can efficiently generate HPCs from hESCs.Our strategy could offer an in vitro model to study early human hematopoietic development.

  12. High-dose chemotherapy and hematopoietic stem cell transplantation for patients with nasopharyngeal cancer. A feasibility study

    International Nuclear Information System (INIS)

    Nasopharyngeal cancer (NPC) is a highly chemosensitive malignancy. The purpose of this study was to evaluate the clinical efficacy of high-dose chemotherapy (HDCT) in combination with hematopoietic stem cell transplantation in patients with locally advanced or metastatic NPC. Nine patients with locally advanced or metastatic NPC were recruited after three to four courses of cisplatin-based chemotherapy followed by a single course of cyclophosphamide 1600 mg/m2 day 1-4, carboplatin 400 mg/m2 day 1-3, and thiotepa 120 mg/m2 day 1-4 or melphalan 120 mg/m2 day 5. Chemoirradiation was administered after HDCT only if the patient had never received radiotherapy or had residual cervical nodes. A median of 8.32 x 106 CD34+ cells/kg was collected. Two patients were rendered disease-free before HDCT, one by massectomy and one by cisplatin-based chemotherapy. All patients recovered rapidly after peripheral blood stem cell transplantation (PBSCT). Among seven assessable patients, response to HDCT was observed in four patients. Only one patient achieved complete response after HDCT. The median time to failure and median survival after HDCT was eight and 18 months, respectively. One patient died of pulmonary hemorrhage two months after transplantation. No long-term disease-free survival was noted. HDCT with autologous PBSCT is feasible with an acceptable toxicity, and can convert partial remission into complete remission. While no long-term disease-free survival was observed in this study, further investigations are needed to establish the role of HDCT in the treatment of NPC. (author)

  13. Beneficial effects of autologous bone marrow-derived mesenchymal stem cells in naturally occurring tendinopathy.

    Directory of Open Access Journals (Sweden)

    Roger Kenneth Whealands Smith

    Full Text Available Tendon injuries are a common age-related degenerative condition where current treatment strategies fail to restore functionality and normal quality of life. This disease also occurs naturally in horses, with many similarities to human tendinopathy making it an ideal large animal model for human disease. Regenerative approaches are increasingly used to improve outcome involving mesenchymal stem cells (MSCs, supported by clinical data where injection of autologous bone marrow derived MSCs (BM-MSCs suspended in marrow supernatant into injured tendons has halved the re-injury rate in racehorses. We hypothesized that stem cell therapy induces a matrix more closely resembling normal tendon than the fibrous scar tissue formed by natural repair. Twelve horses with career-ending naturally-occurring superficial digital flexor tendon injury were allocated randomly to treatment and control groups. 1X10(7 autologous BM-MSCs suspended in 2 ml of marrow supernatant were implanted into the damaged tendon of the treated group. The control group received the same volume of saline. Following a 6 month exercise programme horses were euthanized and tendons assessed for structural stiffness by non-destructive mechanical testing and for morphological and molecular composition. BM-MSC treated tendons exhibited statistically significant improvements in key parameters compared to saline-injected control tendons towards that of normal tendons and those in the contralateral limbs. Specifically, treated tendons had lower structural stiffness (p<0.05 although no significant difference in calculated modulus of elasticity, lower (improved histological scoring of organisation (p<0.003 and crimp pattern (p<0.05, lower cellularity (p<0.007, DNA content (p<0.05, vascularity (p<0.03, water content (p<0.05, GAG content (p<0.05, and MMP-13 activity (p<0.02. Treatment with autologous MSCs in marrow supernatant therefore provides significant benefits compared to untreated tendon repair

  14. Therapeutic neovascularization by autologous transplantation with expanded endothelial progenitor cells from peripheral blood into ischemic hind limbs

    Institute of Scientific and Technical Information of China (English)

    Chun-ling FAN; Ping-jin GAO; Zai-qian CHE; Jian-jun LIU; Jian WEI; Ding-liang ZHU

    2005-01-01

    Aim: To investigate the hypothesis that transplantation with expanded autologous endothelial progenitor cells (EPC) could enhance neovascularization.Methods: Peripheral blood mononuclear cells (PB-MNC) isolated from New Zealand White rabbits were cultured in vitro. At d 7, the adherent cells were collected for autologous transplantation. Rabbits with severe unilateral hind limb ischemia were randomly assigned to receive phosphate-buffered saline or expanded EPC in phosphate-buffered saline, administered by intramuscular injection in 6 sites of the ischemic thigh at postoperative d 7. Neovascularization was monitored by using the calf blood pressure ratio to indicate tissue perfusion, digital subtraction angiography to identify collateral vessel development and histological analysis of capillary density in the ischemic limb at d 35 after surgery. Results: Autologous EPC transplantation produced significant amelioration in ischemic hind limbs,as indicated by a greater calf blood pressure ratio (0.52±0.04 vs 0.42±0.05, P<0.01),angiographic score (1.44±0.06 vs 0.98±0.08, P<0.01) and capillary density in muscle (195.2±5.4/mm2 vs 169.4±6.4/mm2, P<0.05), than controls. Conclusion: Transplantation of autologous expanded EPC can promote neovascularization in ischemic hindlimbs.

  15. Treatment of chronic hepatic cirrhosis with autologous bone marrow stem cells transplantation in rabbits

    International Nuclear Information System (INIS)

    Objective: To evaluate the feasibility of treatment for rabbit model with hepatic cirrhosis by transplantation of autologous bone marrow-derived stem cells via the hepatic artery and evaluate the effect of hepatocyte growth-promoting factors (pHGF) in the treatment of stem cells transplantation to liver cirrhosis. To provide empirical study foundation for future clinical application. Methods: Chronic hepatic cirrhosis models of rabbits were developed by subcutaneous injection with 50% CCl4 0.2 ml/kg. Twenty-five model rabbits were randomly divided into three experimental groups, stem cells transplant group (10), stem cells transplant + pHGF group (10) and control group (5). Autologous bone marrow was harvested from fibia of each rabbit, and stem cells were disassociated using density gradient centrifugation and transplanted into liver via the hepatic artery under fluoroscopic guidance. In the stem cells transplant + pHGF group, the hepatocyte growth-promoting factor was given via intravenous injection with 2 mg/kg every other day for 20 days. Liver function tests were monitored at 4, 8,12 weeks intervals and histopathologic examinations were performed at 12 weeks following transplantation. The data were analyzed using analysis of variance Results: Following transplantation of stern cells, the liver function of rabbits improved gradually. Twelve weeks after transplantation, the activity of ALT and AST decreased from (73.0±10.6) U/L and (152.4± 22.8) U/L to (48.0±1.0) U/L and (86.7±2.1) U/L respectively; and the level of ALB and PTA increased from (27.5±1.8) g/L and 28.3% to (33.2±0.5) g/L and 44.1% respectively. The changes did not have statistically significant difference when compared to the control group (P>0.05). However, in the stem cellstransplant + pHGF group, the activity of ALT and AST decreased to (43.3±0.6) U/L and (78.7±4.0) U/L respectively and the level of ALB and PTA increased to (35.7±0.4) g/L and 50.5% respectively. The difference was

  16. Challenging complications of treatment – human herpes virus 6 encephalitis and pneumonitis in a patient undergoing autologous stem cell transplantation for relapsed Hodgkin's disease: a case report

    Directory of Open Access Journals (Sweden)

    Pauls Sandra

    2009-07-01

    Full Text Available Abstract Background Reactivation of human herpesvirus 6 (HHV-6 occurs frequently in patients after allogeneic stem cell transplantation and is associated with bone-marrow suppression, enteritis, pneumonitis, pericarditis and also encephalitis. After autologous stem cell transplantation or intensive polychemotherapy HHV-6 reactivation is rarely reported. Case report This case demonstrates a severe symptomatic HHV-6 infection with encephalitis and pneumonitis after autologous stem cell transplantation of a patient with relapsed Hodgkin's disease. Conclusion Careful diagnostic work up in patients with severe complications after autologous stem cell transplantation is mandatory to identify uncommon infections.

  17. Autologous peripheral blood stem cell transplantation in malignancies involving bone marrow.

    Science.gov (United States)

    Sica, S; Leone, G; Teofili, L; Pierelli, L; Menichella, G; Di Mario, A; Paoloni, A; Iovino, M S; Bizzi, B

    1991-03-01

    Six patients suffering from refractory malignancies (3 NHL, 1 MM, 1 AML, 1 neuroblastoma) received high dose of chemotherapy and autologous peripheral blood stem cell transplantation (APBSCT). The recruitment of PBSC was performed using conventional salvatage schedules of therapy. The patients received a median of 8.69 MNC/kg bw and 20.87 CFU-GM x 10(4)/kg bw. Prompt engraftment occurred in all patients and the median number of days to achieve WBC greater than 1 x 10(9)/l was 16.5 (range 7-26), PMN greater than 0.5 x 10(9)/l was 21.5 (range 6-37) and PLTs greater than 50 x 10(9)/l was 17.5 (range 4-31). Four patients achieved a complete remission. One patient (neuroblastoma) died of progressive disease after a partial response. One patient died in relapse because of drug related toxicity. PMID:1677914

  18. Purification and characterization of fetal hematopoietic cells that express the common acute lymphoblastic leukemia antigen (CALLA)

    OpenAIRE

    1983-01-01

    Fetal hematopoietic cells that express the common acute lymphoblastic leukemia antigen (CALLA) were purified from both fetal liver and fetal bone marrow by immune rosetting with sheep erythrocytes coated with rabbit anti-mouse immunoglobulin and by fluorescence-activated cell sorting. Dual fluorescence techniques disclosed that these cells were heterogenous with respect to the expression of a series of differentiation and activation antigens defined by monoclonal antibodies. Thus, whereas all...

  19. Wnt-inhibitory factor 1 dysregulation of the bone marrow niche exhausts hematopoietic stem cells

    OpenAIRE

    Schaniel, Christoph; Sirabella, Dario; Qiu, Jiajing; Niu, Xiaohong; Lemischka, Ihor R.; Moore, Kateri A.

    2011-01-01

    The role of Wnt signaling in hematopoietic stem cell fate decisions remains controversial. We elected to dysregulate Wnt signaling from the perspective of the stem cell niche by expressing the pan Wnt inhibitor, Wnt inhibitory factor 1 (Wif1), specifically in osteoblasts. Here we report that osteoblastic Wif1 overexpression disrupts stem cell quiescence, leading to a loss of self-renewal potential. Primitive stem and progenitor populations were more proliferative and elevated in bone marrow a...

  20. Secreted proteome of the murine multipotent hematopoietic progenitor cell line DKmix

    OpenAIRE

    Luecke, N; Templin, C; Muetzelburg, M V; Neumann, D.; Just, I; Pich, A.(IFIC, Universitat de València, CSIC, Apt. Correus 22085, 46071 , València, Spain)

    2010-01-01

    Administration of the multipotent hematopoietic progenitor cell (HPC) line DKmix improved cardiac function after myocardial infarction and accelerated dermal wound healing due to paracrine mechanisms. The aim of this study was to analyse the secreted proteins of DKmix cells in order to identify the responsible paracrine factors and assess their relevance to the wide spectrum of therapeutic effects. A mass spectrometry (MS)-based approach was used to identify secreted proteins of DKmix cells. ...