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  1. Stem Cell Transplant

    MedlinePlus

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

  2. Intravenous apoptotic cell infusion as a cell-based therapy toward improving hematopoietic cell transplantation outcome.

    PubMed

    Saas, Philippe; Gaugler, Béatrice; Perruche, Sylvain

    2010-10-01

    Allogeneic hematopoietic cell transplantation (AHCT) is an efficient therapy for different malignant and nonmalignant hematological diseases. However, the use of this therapeutic approach is still limited by some severe toxic side effects, mainly graft-versus-host disease (GvHD). Today, the risk of fatal GvHD restrains the wider application of AHCT to many patients in need of an effective therapy for their high-risk hematologic malignancies. Thus, new strategies, including cell-based therapy approaches, are required. We propose to use intravenous donor apoptotic leukocyte infusion to improve AHCT outcome. In experimental AHCT models, we demonstrated that intravenous apoptotic leukocyte infusion, simultaneously with allogeneic bone marrow grafts, favors hematopoietic engraftment, prevents allo-immunization, and delays acute GvHD onset. Here, we review the different mechanisms and the potential beneficial effects associated with the immunomodulatory properties of apoptotic cells in the AHCT setting. © 2010 New York Academy of Sciences.

  3. Exploring cell-based tolerance strategies for hand and face transplantation.

    PubMed

    Fryer, Madeline; Grahammer, Johanna; Khalifian, Saami; Furtmüller, Georg J; Lee, W P Andrew; Raimondi, Giorgio; Brandacher, Gerald

    2015-01-01

    Broader clinical application of reconstructive hand and face transplantation is hindered by the need for lifelong immunosuppression for allograft maintenance. In this review, we summarize various cell-based approaches to tolerance induction currently under investigation in both clinical and pre-clinical models to alleviate the need for chronic immunosuppression. These include strategies to induce mixed hematopoietic chimerism, therapy with T and B regulatory cells, regulatory macrophages, tolerogenic dendritic cells, and mesenchymal stem cells. The vascularized, intragraft bone components inherent to reconstructive transplants serve as a continuous source of donor-derived hematopoietic cells, and make hand and face transplants uniquely well suited for cell-based approaches to tolerance that may ultimately tilt the risk-benefit balance for these life-changing, but not life-saving, procedures.

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

    PubMed

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

    2008-01-01

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

  5. Islet Cell Transplantation

    MedlinePlus

    ... person who has type 1 diabetes must take insulin daily to live. Transplanted islet cells, however, can take over the work of the destroyed cells. The beta cells in these islets will begin to make and release insulin. Researchers hope islet transplantation will help people with ...

  6. Transplantation of Airway Epithelial Stem/Progenitor Cells: A Future for Cell-Based Therapy.

    PubMed

    Ghosh, Moumita; Ahmad, Shama; White, Carl W; Reynolds, Susan D

    2017-01-01

    Cell therapy has the potential to cure disease through replacement of malfunctioning cells. Although the tissue stem cell (TSC) is thought to be the optimal therapeutic cell, transplantation of TSC/progenitor cell mixtures has saved lives. We previously purified the mouse tracheobronchial epithelial TSCs and reported that in vitro amplification generated numerous TSCs. However, these cultures also contained TSC-derived progenitor cells and TSC repurification by flow cytometry compromised TSC self-renewal. These limitations prompted us to determine if a TSC/progenitor cell mixture would repopulate the injured airway epithelium. We developed a cell transplantation protocol and demonstrate that transplanted mouse and human tracheobronchial epithelial TSC/progenitor cell mixtures are 20-25% of airway epithelial cells, actively contribute to epithelial repair, and persist for at least 43 days. At 2 weeks after transplantation, TSCs/progenitor cells differentiated into the three major epithelial cell types: basal, secretory, and ciliated. We conclude that cell therapy that uses adult tracheobronchial TSCs/progenitor cells is an effective therapeutic option.

  7. Stem cell-based approaches to improve nerve regeneration: potential implications for reconstructive transplantation?

    PubMed

    Khalifian, Saami; Sarhane, Karim A; Tammia, Markus; Ibrahim, Zuhaib; Mao, Hai-Quan; Cooney, Damon S; Shores, Jaimie T; Lee, W P Andrew; Brandacher, Gerald

    2015-02-01

    Reconstructive transplantation has become a viable option to restore form and function after devastating tissue loss. Functional recovery is a key determinant of overall success and critically depends on the quality and pace of nerve regeneration. Several molecular and cell-based therapies have been postulated and tested in pre-clinical animal models to enhance nerve regeneration. Schwann cells remain the mainstay of research focus providing neurotrophic support and signaling cues for regenerating axons. Alternative cell sources such as mesenchymal stem cells and adipose-derived stromal cells have also been tested in pre-clinical animal models and in clinical trials due to their relative ease of harvest, rapid expansion in vitro, minimal immunogenicity, and capacity to integrate and survive within host tissues, thereby overcoming many of the challenges faced by culturing of human Schwann cells and nerve allografting. Induced pluripotent stem cell-derived Schwann cells are of particular interest since they can provide abundant, patient-specific autologous Schwann cells. The majority of experimental evidence on cell-based therapies, however, has been generated using stem cell-seeded nerve guides that were developed to enhance nerve regeneration across "gaps" in neural repair. Although primary end-to-end repair is the preferred method of neurorrhaphy in reconstructive transplantation, mechanistic studies elucidating the principles of cell-based therapies from nerve guidance conduits will form the foundation of further research employing stem cells in end-to-end repair of donor and recipient nerves. This review presents key components of nerve regeneration in reconstructive transplantation and highlights the pre-clinical studies that utilize stem cells to enhance nerve regeneration.

  8. Transplantation of Mesenchymal Stem Cells for Acute Spinal Cord Injury in Rats: Comparative Study between Intralesional Injection and Scaffold Based Transplantation.

    PubMed

    Kim, Yoon Chung; Kim, Young Hoon; Kim, Jang Woon; Ha, Kee Yong

    2016-09-01

    Experimental stem cell therapy for spinal cord injury (SCI) has been extensively investigated. The selection of effective cell transplantation route is also an important issue. Although various types of scaffold have been widely tried as a carrier of stem cells to the injured spinal cord, there was little comparative study to investigate the efficacy of transplantation comparing with conventional transplantation route. A total of 48 Sprague-Dawley rats were subjected to standardized SCI, followed by transplantation of allogeneic mesenchymal stem cells (MSCs), either via intralesional injection (IL group), or via the poly (lactic-co-glycolic acid) (PLGA) scaffold (IP group) or chitosan scaffold (IC group). Engraftment and differentiation of the transplanted cells, expression of neurotrophic factors in the injured spinal cord, and functional recovery were compared with those of the control group. The mean numbers of engrafted MSCs in the IL, IP, and IC groups were 20.6 ± 0.7, 25.6 ± 1.7 and 26.7 ± 1.8 cells/high power filed (HPF), respectively. Results showed higher success rate of MSCs engraftment in the scaffold groups compared to the IL group. Expression of neuroprotective growth factors in the SCI lesions showed no significant differences between the IL, IP, and IC groups. The mean Basso, Beattie and Bresnahan locomotor scales at 6 weeks post-transplantation in the IL, IP, IC, and control groups were 7.9 ± 1.1, 7.9 ± 2.1, 8.7 ± 2.1, and 2.9 ± 1.0, respectively. The functional improvement was most excellent in the IC group. The scaffold based MSC transplantation for acute SCI presented the better cell engraftment and neuroprotective effect compared to the intralesional injection transplantation.

  9. Post-transplantation Cyclophosphamide and Sirolimus after Haploidentical Hematopoietic Stem Cell Transplantation Using a Treosulfan-based Myeloablative Conditioning and Peripheral Blood Stem Cells.

    PubMed

    Cieri, Nicoletta; Greco, Raffaella; Crucitti, Lara; Morelli, Mara; Giglio, Fabio; Levati, Giorgia; Assanelli, Andrea; Carrabba, Matteo G; Bellio, Laura; Milani, Raffaella; Lorentino, Francesca; Stanghellini, Maria Teresa Lupo; De Freitas, Tiago; Marktel, Sarah; Bernardi, Massimo; Corti, Consuelo; Vago, Luca; Bonini, Chiara; Ciceri, Fabio; Peccatori, Jacopo

    2015-08-01

    Haploidentical hematopoietic stem cell transplantation (HSCT) performed using bone marrow (BM) grafts and post-transplantation cyclophosphamide (PTCy) has gained much interest for the excellent toxicity profile after both reduced-intensity and myeloablative conditioning. We investigated, in a cohort of 40 high-risk hematological patients, the feasibility of peripheral blood stem cells grafts after a treosulfan-melphalan myeloablative conditioning, followed by a PTCy and sirolimus-based graft-versus-host disease (GVHD) prophylaxis (Sir-PTCy). Donor engraftment occurred in all patients, with full donor chimerism achieved by day 30. Post-HSCT recovery of lymphocyte subsets was broad and fast, with a median time to CD4 > 200/μL of 41 days. Cumulative incidences of grade II to IV and III-IV acute GVHD were 15% and 7.5%, respectively, and were associated with a significant early increase in circulating regulatory T cells at day 15 after HSCT, with values < 5% being predictive of subsequent GVHD occurrence. The 1-year cumulative incidence of chronic GVHD was 20%. Nonrelapse mortality (NRM) at 100 days and 1 year were 12% and 17%, respectively. With a median follow-up for living patients of 15 months, the estimated 1-year overall and disease-free survival (DFS) was 56% and 48%, respectively. Outcomes were more favorable in patients who underwent transplantation in complete remission (1-year DFS 71%) versus patients who underwent transplantation with active disease (DFS, 34%; P = .01). Overall, myeloablative haploidentical HSCT with peripheral blood stem cells (PBSC) and Sir-PTCy is a feasible treatment option: the low rates of GVHD and NRM as well as the favorable immune reconstitution profile pave the way for a prospective comparative trial comparing BM and PBSC in this specific transplantation setting.

  10. Stem Cell Transplants (For Teens)

    MedlinePlus

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

  11. Stem Cell Transplants (For Teens)

    MedlinePlus

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

  12. Hematopoietic Cell Transplantation after Solid Organ Transplantation.

    PubMed

    Doney, Kristine C; Mielcarek, Marco; Stewart, F Marc; Appelbaum, Frederick R

    2015-12-01

    Solid organ transplantation (SOT) followed by hematopoietic cell transplantation (HCT) has been used to treat a single disease with multiorgan involvement or 2 separate diseases, the first requiring SOT and the second often a possible complication of SOT. Results of such serial transplants have been reported sporadically in the literature, usually as single case studies. Thirteen autologous and 27 allogeneic HCTs after SOT published previously are summarized. A more detailed review is provided for an additional 16 patients transplanted at a single institution, 8 of whom had autologous and 8 of whom had allogeneic HCT after SOT. Five of 8 autologous transplant recipients are alive a median of 4.6 years after HCT. Four of 8 allogeneic HCT recipients are alive a median of 8.7 years after HCT. In carefully selected patients, HCT after SOT is feasible and associated with a low incidence of either solid organ or hematopoietic cell rejection.

  13. A critical care and transplant-based approach to acute respiratory failure after hematopoietic stem cell transplantation in children

    PubMed Central

    Morrison, R. Ray

    2016-01-01

    Acute respiratory failure contributes significantly to non-relapse mortality following allogeneic hematopoietic stem cell transplantation. Although there is a trend of improved survival over time, mortality remains unacceptably high. An understanding of the pathophysiology of early respiratory failure, opportunities for targeted therapy, assessment of the patient at risk, optimal use of non-invasive positive pressure ventilation, strategies to improve alveolar recruitment, appropriate fluid management, care of the patient with chronic lung disease, and importantly, a team approach between critical care and transplant services may improve outcomes. PMID:26409244

  14. Mesothelial cell transplantation.

    PubMed

    Witkowicz, Joanna

    2008-05-01

    Mesothelial cells are an integral part of the peritoneum and play an important role in maintaining its structural and functional properties. In the recent years a number of studies on mesothelial cells have been performed to evaluate the localization, secretional properties and the ability of regeneration and transdifferentiation of these cells. They are also involved in the repair of the peritoneum damage following surgery or peritonitis. Mesothelial cells produce several cytokines, growth factors and extracellular matrix components, possessing anti-inflammatory and immunomodulatory properties. Because of their plasticity, these cells are able to form a new cell type like fibroblast, endothelial and smooth muscle cell, chondrocyte, osteoblast, adipocyte or neuron. The first step involves mesothelial cell transdifferentiation into progenitor cells with the capacity of further differentiation. In this paper the current knowledge concerning the mesothelial cell differentiation and transplantation has been reviewed. Own mesothelial cells of a patient are used in transplantation. They are sampled, cultured in vitro and then they can be used in the prevention and treatment of post-operative abdominal adhesions, incisional hernias, repair of peritoneal membrane of patients on long-term peritoneal dialysis, the prevention of ischemic myocardial damage, nerve regeneration and genetically modified recombinant protein secretion. Inevitably, more potential applications of transplanted mesothelial cell will be available over the next few years.

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

    PubMed

    Li, Runhui

    2012-06-05

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

  16. IAP-Based Cell Sorting Results in Homogeneous Transplantable Dopaminergic Precursor Cells Derived from Human Pluripotent Stem Cells.

    PubMed

    Lehnen, Daniela; Barral, Serena; Cardoso, Tiago; Grealish, Shane; Heuer, Andreas; Smiyakin, Andrej; Kirkeby, Agnete; Kollet, Jutta; Cremer, Harold; Parmar, Malin; Bosio, Andreas; Knöbel, Sebastian

    2017-09-19

    Human pluripotent stem cell (hPSC)-derived mesencephalic dopaminergic (mesDA) neurons can relieve motor deficits in animal models of Parkinson's disease (PD). Clinical translation of differentiation protocols requires standardization of production procedures, and surface-marker-based cell sorting is considered instrumental for reproducible generation of defined cell products. Here, we demonstrate that integrin-associated protein (IAP) is a cell surface marker suitable for enrichment of hPSC-derived mesDA progenitor cells. Immunomagnetically sorted IAP(+) mesDA progenitors showed increased expression of ventral midbrain floor plate markers, lacked expression of pluripotency markers, and differentiated into mature dopaminergic (DA) neurons in vitro. Intrastriatal transplantation of IAP(+) cells sorted at day 16 of differentiation in a rat model of PD resulted in functional recovery. Grafts from sorted IAP(+) mesDA progenitors were more homogeneous in size and DA neuron density. Thus, we suggest IAP-based sorting for reproducible prospective enrichment of mesDA progenitor cells in clinical cell replacement strategies. Copyright © 2017 Miltenyi Biotec GmbH. Published by Elsevier Inc. All rights reserved.

  17. Magnetic Cell Labeling of Primary and Stem Cell-Derived Pig Hepatocytes for MRI-Based Cell Tracking of Hepatocyte Transplantation

    PubMed Central

    Roach, Dwayne R.; Garrett, Wesley M.; Welch, Glenn; Caperna, Thomas J.; Talbot, Neil C.; Shapiro, Erik M.

    2015-01-01

    Pig hepatocytes are an important investigational tool for optimizing hepatocyte transplantation schemes in both allogeneic and xenogeneic transplant scenarios. MRI can be used to serially monitor the transplanted cells, but only if the hepatocytes can be labeled with a magnetic particle. In this work, we describe culture conditions for magnetic cell labeling of cells from two different pig hepatocyte cell sources; primary pig hepatocytes (ppHEP) and stem cell-derived hepatocytes (PICM-19FF). The magnetic particle is a micron-sized iron oxide particle (MPIO) that has been extensively studied for magnetic cell labeling for MRI-based cell tracking. ppHEP could endocytose MPIO with labeling percentages as high as 70%, achieving iron content as high as ~55 pg/cell, with >75% viability. PICM-19FF had labeling >97%, achieving iron content ~38 pg/cell, with viability >99%. Extensive morphological and functional assays indicated that magnetic cell labeling was benign to the cells. The results encourage the use of MRI-based cell tracking for the development and clinical use of hepatocyte transplantation methodologies. Further, these results generally highlight the importance of functional cell assays in the evaluation of contrast agent biocompatibility. PMID:25856627

  18. Magnetic cell labeling of primary and stem cell-derived pig hepatocytes for MRI-based cell tracking of hepatocyte transplantation.

    PubMed

    Roach, Dwayne R; Garrett, Wesley M; Welch, Glenn; Caperna, Thomas J; Talbot, Neil C; Shapiro, Erik M

    2015-01-01

    Pig hepatocytes are an important investigational tool for optimizing hepatocyte transplantation schemes in both allogeneic and xenogeneic transplant scenarios. MRI can be used to serially monitor the transplanted cells, but only if the hepatocytes can be labeled with a magnetic particle. In this work, we describe culture conditions for magnetic cell labeling of cells from two different pig hepatocyte cell sources; primary pig hepatocytes (ppHEP) and stem cell-derived hepatocytes (PICM-19FF). The magnetic particle is a micron-sized iron oxide particle (MPIO) that has been extensively studied for magnetic cell labeling for MRI-based cell tracking. ppHEP could endocytose MPIO with labeling percentages as high as 70%, achieving iron content as high as ~55 pg/cell, with >75% viability. PICM-19FF had labeling >97%, achieving iron content ~38 pg/cell, with viability >99%. Extensive morphological and functional assays indicated that magnetic cell labeling was benign to the cells. The results encourage the use of MRI-based cell tracking for the development and clinical use of hepatocyte transplantation methodologies. Further, these results generally highlight the importance of functional cell assays in the evaluation of contrast agent biocompatibility.

  19. Prospects of apoptotic cell-based therapies for transplantation and inflammatory diseases.

    PubMed

    Saas, Philippe; Kaminski, Sandra; Perruche, Sylvain

    2013-10-01

    Apoptotic cell removal or interactions of early-stage apoptotic cells with immune cells are associated with an immunomodulatory microenvironment that can be harnessed to exert therapeutic effects. While the involved immune mechanisms are still being deciphered, apoptotic cell infusion has been tested in different experimental models where inflammation is deregulated. This includes chronic and acute inflammatory disorders such as arthritis, contact hypersensitivity and acute myocardial infarction. Apoptotic cell infusion has also been used in transplantation settings to prevent or treat acute and chronic rejection, as well as to limit acute graft-versus-host disease associated with allogeneic hematopoietic cell transplantation. Here, we review the mechanisms involved in apoptotic cell-induced immunomodulation and data obtained in preclinical models of transplantation and inflammatory diseases.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-05-01

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

  2. Stem cell transplantation for treating Duchenne muscular dystrophy: A Web of Science-based literature analysis.

    PubMed

    Yang, Xiaofeng

    2012-08-05

    To identify global research trends in stem cell transplantation for treating Duchenne muscular dystrophy using a bibliometric analysis of Web of Science. We performed a bibliometric analysis of studies on stem cell transplantation for treating Duchenne muscular dystrophy from 2002 to 2011 retrieved from Web of Science. (a) peer-reviewed published articles on stem cell transplantation for treating Duchenne muscular dystrophy indexed in Web of Science; (b) original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material, and news items; and (c) publication between 2002 and 2011. (a) articles that required manual searching or telephone access; (b) documents that were not published in the public domain; and (c) corrected papers. (1) Annual publication output; (2) distribution according to subject areas; (3) distribution according to journals; (4) distribution according to country; (5) distribution according to institution; (6) distribution according to institution in China; (7) distribution according to institution that cooperated with Chinese institutions; (8) top-cited articles from 2002 to 2006; (9) top-cited articles from 2007 to 2011. A total of 318 publications on stem cell transplantation for treating Duchenne muscular dystrophy were retrieved from Web of Science from 2002 to 2011, of which almost half derived from American authors and institutes. The number of publications has gradually increased over the past 10 years. Most papers appeared in journals with a focus on gene and molecular research, such as Molecular Therapy, Neuromuscular Disorders, and PLoS One. The 10 most-cited papers from 2002 to 2006 were mostly about different kinds of stem cell transplantation for muscle regeneration, while the 10 most-cited papers from 2007 to 2011 were mostly about new techniques of stem cell transplantation for treating Duchenne muscular dystrophy. The publications on stem cell transplantation for treating Duchenne muscular

  3. Stem Cell Transplants (For Parents)

    MedlinePlus

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

  4. Plasmid-based genetic modification of human bone marrow-derived stromal cells: analysis of cell survival and transgene expression after transplantation in rat spinal cord.

    PubMed

    Ronsyn, Mark W; Daans, Jasmijn; Spaepen, Gie; Chatterjee, Shyama; Vermeulen, Katrien; D'Haese, Patrick; Van Tendeloo, Viggo Fi; Van Marck, Eric; Ysebaert, Dirk; Berneman, Zwi N; Jorens, Philippe G; Ponsaerts, Peter

    2007-12-14

    Bone marrow-derived stromal cells (MSC) are attractive targets for ex vivo cell and gene therapy. In this context, we investigated the feasibility of a plasmid-based strategy for genetic modification of human (h)MSC with enhanced green fluorescent protein (EGFP) and neurotrophin (NT)3. Three genetically modified hMSC lines (EGFP, NT3, NT3-EGFP) were established and used to study cell survival and transgene expression following transplantation in rat spinal cord. First, we demonstrate long-term survival of transplanted hMSC-EGFP cells in rat spinal cord under, but not without, appropriate immune suppression. Next, we examined the stability of EGFP or NT3 transgene expression following transplantation of hMSC-EGFP, hMSC-NT3 and hMSC-NT3-EGFP in rat spinal cord. While in vivo EGFP mRNA and protein expression by transplanted hMSC-EGFP cells was readily detectable at different time points post-transplantation, in vivo NT3 mRNA expression by hMSC-NT3 cells and in vivo EGFP protein expression by hMSC-NT3-EGFP cells was, respectively, undetectable or declined rapidly between day 1 and 7 post-transplantation. Further investigation revealed that the observed in vivo decline of EGFP protein expression by hMSC-NT3-EGFP cells: (i) was associated with a decrease in transgenic NT3-EGFP mRNA expression as suggested following laser capture micro-dissection analysis of hMSC-NT3-EGFP cell transplants at day 1 and day 7 post-transplantation, (ii) did not occur when hMSC-NT3-EGFP cells were transplanted subcutaneously, and (iii) was reversed upon re-establishment of hMSC-NT3-EGFP cell cultures at 2 weeks post-transplantation. Finally, because we observed a slowly progressing tumour growth following transplantation of all our hMSC cell transplants, we here demonstrate that omitting immune suppressive therapy is sufficient to prevent further tumour growth and to eradicate malignant xenogeneic cell transplants. In this study, we demonstrate that genetically modified hMSC lines can survive

  5. Plasmid-based genetic modification of human bone marrow-derived stromal cells: analysis of cell survival and transgene expression after transplantation in rat spinal cord

    PubMed Central

    Ronsyn, Mark W; Daans, Jasmijn; Spaepen, Gie; Chatterjee, Shyama; Vermeulen, Katrien; D'Haese, Patrick; Van Tendeloo, Viggo FI; Van Marck, Eric; Ysebaert, Dirk; Berneman, Zwi N; Jorens, Philippe G; Ponsaerts, Peter

    2007-01-01

    Background Bone marrow-derived stromal cells (MSC) are attractive targets for ex vivo cell and gene therapy. In this context, we investigated the feasibility of a plasmid-based strategy for genetic modification of human (h)MSC with enhanced green fluorescent protein (EGFP) and neurotrophin (NT)3. Three genetically modified hMSC lines (EGFP, NT3, NT3-EGFP) were established and used to study cell survival and transgene expression following transplantation in rat spinal cord. Results First, we demonstrate long-term survival of transplanted hMSC-EGFP cells in rat spinal cord under, but not without, appropriate immune suppression. Next, we examined the stability of EGFP or NT3 transgene expression following transplantation of hMSC-EGFP, hMSC-NT3 and hMSC-NT3-EGFP in rat spinal cord. While in vivo EGFP mRNA and protein expression by transplanted hMSC-EGFP cells was readily detectable at different time points post-transplantation, in vivo NT3 mRNA expression by hMSC-NT3 cells and in vivo EGFP protein expression by hMSC-NT3-EGFP cells was, respectively, undetectable or declined rapidly between day 1 and 7 post-transplantation. Further investigation revealed that the observed in vivo decline of EGFP protein expression by hMSC-NT3-EGFP cells: (i) was associated with a decrease in transgenic NT3-EGFP mRNA expression as suggested following laser capture micro-dissection analysis of hMSC-NT3-EGFP cell transplants at day 1 and day 7 post-transplantation, (ii) did not occur when hMSC-NT3-EGFP cells were transplanted subcutaneously, and (iii) was reversed upon re-establishment of hMSC-NT3-EGFP cell cultures at 2 weeks post-transplantation. Finally, because we observed a slowly progressing tumour growth following transplantation of all our hMSC cell transplants, we here demonstrate that omitting immune suppressive therapy is sufficient to prevent further tumour growth and to eradicate malignant xenogeneic cell transplants. Conclusion In this study, we demonstrate that genetically

  6. Allogeneic Stem Cell Transplantation in Congenital Hemoglobinopathies Using a Tailored Busulfan-Based Conditioning Regimen: Single-Center Experience.

    PubMed

    Zaidman, Irina; Rowe, Jacob M; Khalil, Abdalla; Ben-Arush, Myriam; Elhasid, Ronit

    2016-06-01

    Hematopoietic stem cell transplantation (HSCT) is the only proven curative option for patients with hemoglobinopathies, both thalassemia and sickle cell anemia (SCA). A busulfan-based myeloablative conditioning regimen is the standard of care for HSCT in these patients, although increased treatment-related morbidity, including veno-occlusive disease (VOD), has been demonstrated. Thirty-eight pediatric patients, median age 8 years (range, 6 months to 22 years), suffering from hemoglobinopathy were treated at Rambam Medical Center in Haifa, Israel, between 1998 and 2011. Thirty-four patients had thalassemia major and 4 had SCA. The 38 patients underwent 40 HSCTs, 34 of which were first transplants and 6 second transplants. Most transplants (32/40) were from matched sibling donors. Sources of stem cells were peripheral blood in 30 transplants, bone marrow in 7 transplants, and cord blood in 3 transplants. All received different customized busulfan-based conditioning regimens tailored by pharmacokinetic analysis of busulfan levels. Primary engraftment occurred in 37 of 40 transplants. Neutrophil engraftment (>.5 × 10(9)/L) occurred at a median of 15.3 days post-transplantation (range, 10 to 45). Platelet transfusion independence (>20 × 10(9)/L) occurred at a median of 22.3 days (range, 11 to 60). The rate of 5-year overall survival for thalassemia patients after first transplantation was 90.5% ± 5.3%. The rate of 5-year thalassemia-free survival was 81.7% ± 6.8%. Cumulative incidence of acute graft-versus-host disease (GVHD) was 17.6%. Rate of grades III to IV GVHD was 8.8%. Cumulative incidence of chronic GVHD was 23.5%, with 11.8% incidence of extensive chronic GVHD. One patient developed VOD. Full donor chimerism occurred in 36.4% of patients with class 1 + 2 thalassemia, compared with 78.6% in class 3 thalassemia (P = .049). Overall survival above 90% in patients undergoing their first transplant was demonstrated using busulfan-based

  7. Reduced intensity allogeneic hematopoietic stem cell transplantion for MDS using tacrolimus/sirolimus-based GVHD prophylaxis

    PubMed Central

    Nakamura, Ryotaro; Palmer, Joycelynne M.; O'Donnell, Margaret R.; Stiller, Tracey; Thomas, Sandra H.; Chao, Joseph; Alvarnas, Joseph; Parker, Pablo M.; Pullarkat, Vinod; Maegawa, Rodrigo; Stein, Anthony S.; Snyder, David S.; Bhatia, Ravi; Chang, Karen; Wang, Shirong; Cai, Ji-Lian; Senitzer, David; Forman, Stephen J.

    2012-01-01

    We report a consecutive series of 59 patients with MDS who underwent reduced-intensity hematopoietic stem cell transplantation (RI-HSCT) with fludarabine/melphalan conditioning and tacrolimus/sirolimus-based GVHD prophylaxis. Two-year OS, EFS, and relapse incidences were 75.1%, 65.2%, and 20.9%, respectively. The cumulative incidence of non-relapse mortality at 100 days, 1 year, and 2 years was 3.4%, 8.5%, and 10.5%, respectively. The incidence of grade II-IV acute GVHD was 35.4%; grade III-IV was 18.6%. Forty of 55 evaluable patients developed chronic GVHD, 35 extensive grade. This RI-HSCT protocol produces encouraging outcomes in MDS patients, and tacrolimus/sirolimus-based GVHD prophylaxis may contribute to that promising result. PMID:22677229

  8. Stem/precursor cell-based CNS therapy: the importance of circumventing immune suppression by transplanting autologous cells.

    PubMed

    Kulbatski, Iris

    2010-09-01

    Stem/precursor cell (SPC) therapy for neurodegeneration and neurotrauma has enormous therapeutic potential, but despite ongoing research efforts the success of clinical trials remains limited. Therapies that utilize immune suppression in combination with SPC transplantation have thus far failed to consider the beneficial role of the immune system in central nervous system (CNS) recovery. Systemic immune suppression may prevent neural repair, and in some cases exacerbate the underlying disorder. Until about a decade ago, immunosuppression for CNS disorders was viewed as a therapeutic target, based on the perception that all immune activity in the CNS was destructive. However, recent studies show that the infiltration of blood-borne immune cells into the CNS following neurotrauma and during chronic neurodegeneration promote CNS protection and regeneration. In the context of SPC therapies, although immune suppression prevents rejection of non-autologous cell grafts, it also prevents the restorative immune response by eliminating the immune mediated guidance cues that are required for SPCs to migrate to the location they are needed, and preventing SPC-mediated immunomodulation. This article argues in favor of transplanting autologous SPCs, particularly bone marrow derived cells. The therapeutic use of autologous SPCs for neural repair circumvents the need for concomitant immune suppression, exploits the immunomodulatory capacity of these cells, and maintains the immune niche that supports neural repair and is required to guide these cells to their appropriate locations. Overall, such an approach accommodates the requirements for translational therapeutics, and provides a standardized platform for reconciling the inherent controversies in the science.

  9. Use of stem cell transplantation to treat epilepsy: A Web of Science-based literature analysis.

    PubMed

    Yin, Zhongmin; Dong, Yushu; Zhang, Jiyang; Wang, Li

    2012-11-25

    To identify global research trends in the use of stem cell transplantation to treat epilepsy. We performed a bibliometric analysis of studies on the use of stem cell transplantation to treat epilepsy during 2002-2011, retrieved from Web of Science, using the key words epilepsy or epileptic or epilepticus or seizure and "stem cell". (a) peer-reviewed published articles on the use of stem cell transplantation to treat epilepsy indexed in Web of Science; (b) original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material, and news items. (a) Annual publication output; (b) type of publication; (c) publication by research field; (d) publication by journal; (e) publication by author; (f) publication by country and institution; (g) publications by institution in China; (h) most-cited papers; and (i) papers published by Chinese authors or institutions. A total of 460 publications on the use of stem cell transplantation to treat epilepsy were retrieved from Web of Science, 2002-2011. The number of publications gradually increased over the 10-year study period. Articles and reviews constituted the major types of publications. More than half of the studies were in the field of neuroscience/neurology. The most prolific journals for this topic were Epilepsia, Bone Marrow Transplantation, and Journal of Neuroscience. Of the 460 publications, almost half came from American authors and institutions; relatively few papers were published by Chinese authors or institutions. Literature on stem cell transplantation for epilepsy includes many reports of basic research, but few of clinical trials or treatments. Exact effects are not yet evaluated. Epilepsy rehabilitation is a long-term, complex, and comprehensive system engineering. With advances in medical development, some effective medical, social and educational measures are needed to facilitate patient's treatment and training and accelerate the recovery of life ability, learning ability

  10. Stem cells and transplant arteriosclerosis.

    PubMed

    Xu, Qingbo

    2008-05-09

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

  11. Phase II Study of Nonmyeloablative Allogeneic Bone Marrow Transplantation for B Cell Lymphoma with Post-Transplantation Rituximab and Donor Selection Based First on Non-HLA Factors.

    PubMed

    Kanakry, Jennifer A; Gocke, Christopher D; Bolaños-Meade, Javier; Gladstone, Douglas E; Swinnen, Lode J; Blackford, Amanda L; Fuchs, Ephraim J; Huff, Carol Ann; Borrello, Ivan; Matsui, William H; Brodsky, Robert A; Rosner, Gary L; Shanbhag, Satish; Luznik, Leo; Jones, Richard J; Ambinder, Richard F; Kasamon, Yvette L

    2015-12-01

    Outcomes of nonmyeloablative (NMA), HLA-haploidentical (haplo), related-donor allogeneic blood or marrow transplantation (allo-BMT) with high-dose post-transplantation cyclophosphamide (PTCy) appear to be similar to those using HLA-matched donors. Thus, it may be possible to prioritize donor factors other than HLA matching that could enhance antitumor activity. The Fc receptor polymorphism FCGR3A-158VV may confer greater sensitivity to rituximab than FCGR3A-158FF. In a prospective phase II study of NMA, related-donor allo-BMT with PTCy and post-transplantation rituximab for patients with B cell lymphomas, we hypothesized that donor selection that prioritized FCGR3A-158 polymorphism over HLA matching would be feasible, safe, and improve outcomes. The primary endpoint was 1-year progression-free survival (PFS). Of 83 patients transplanted (median age, 59 years), 69 (83%) received haplo grafts. Fifty-four (65%) received a graft that maintained or improved their Fc receptor polymorphism status. With 2.6-year median follow-up, the 1-year PFS and overall survival (OS) probabilities were 71% and 86%, respectively, with 1-year relapse and nonrelapse mortality (NRM) probabilities of 20% and 8%. At 1 year, the probability of acute grades II to IV graft-versus-host disease (GVHD) was 41%, with acute grades III to IV GVHD probability of 5% and chronic GVHD probability of 11%. Among haplo transplants, the 1-year probabilities of PFS, OS, relapse, and NRM were 70%, 83%, 20%, and 10%, respectively. No differences in outcomes were observed based on donor FCGR3A-158 polymorphism. Excess infection risk was not apparent with post-transplantation rituximab. Although donor selection based on FCGR3A-158 polymorphism was not shown to influence PFS, this study suggests that donor selection based on criteria other than best HLA match is feasible and safe. This study opens the way for the future investigation of donor prioritization based on promising non-HLA factors that may improve

  12. Hematopoietic stem cell transplantation in thalassemia and sickle cell anemia.

    PubMed

    Lucarelli, Guido; Isgrò, Antonella; Sodani, Pietro; Gaziev, Javid

    2012-05-01

    The globally widespread single-gene disorders β-thalassemia and sickle cell anemia (SCA) can only be cured by allogeneic hematopoietic stem cell transplantation (HSCT). HSCT treatment of thalassemia has substantially improved over the last two decades, with advancements in preventive strategies, control of transplant-related complications, and preparative regimens. A risk class-based transplantation approach results in disease-free survival probabilities of 90%, 84%, and 78% for class 1, 2, and 3 thalassemia patients, respectively. Because of disease advancement, adult thalassemia patients have a higher risk for transplant-related toxicity and a 65% cure rate. Patients without matched donors could benefit from haploidentical mother-to-child transplantation. There is a high cure rate for children with SCA who receive HSCT following myeloablative conditioning protocols. Novel non-myeloablative transplantation protocols could make HSCT available to adult SCA patients who were previously excluded from allogeneic stem cell transplantation.

  13. Subsequent vitiligo after hematopoietic stem cell transplantation: A nationwide population-based cohort study from Korea.

    PubMed

    Bae, Jung Min; Choi, Kwang Hyun; Jung, Han Mi; Kim, Sook Young; Kim, Miri; Kim, Gyung Moon; Yu, Dong Soo; Lee, Young Bok

    2017-03-01

    Subsequent vitiligo after hematopoietic stem cell transplantation (HSCT) has been described sporadically in case series. To investigate the incidence and risk factors of subsequent vitiligo after HSCT. A nationwide, population-based cohort study was performed using the Korean National Health Insurance Claims Database from 2009 to 2013. All HSCT recipients who had undergone HSCT between 2010 and 2011 and not treatment for vitiligo in 2009 (to exclude preexisting active vitiligo) were included in the HSCT recipient group, and an age- and sex-matched control group without HSCT was also established. A total of 2747 HSCT recipients and 8241 controls were enrolled. Newly acquired vitiligo occurred in 1.06% of HSCT recipients between 2010 and 2013, and there was a significant increase (OR 3.130, 95% CI 1.859-5.271) in cases of vitiligo in HSCT recipients compared with controls (0.34%). Allogeneic HSCT (OR 5.593, 95% CI 1.628-19.213) and bone marrow-sourced stem cells (as compared with peripheral blood-sourced stem cells; OR 2.492, 95% CI 1.114-5.576) were independently associated with the development of vitiligo after HSCT. Medical record review was not available. Vitiligo developed at a significantly increased rate after HSCT compared with controls. Allogeneic HSCT and bone marrow-sourced stem cells were independent risk factors. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  14. Therapeutic drug monitoring-guided dosing of busulfan differs from weight-based dosing in hematopoietic stem cell transplant patients.

    PubMed

    Salman, Bushra; Al-Za'abi, Mohammed; Al-Huneini, Mohammed; Dennison, David; Al-Rawas, Abdulhakeem; Al-Kindi, Salam; Al-Farsi, Khalil; Tauro, Melanie; Al-Khabori, Murtadha

    2017-06-01

    Busulfan (Bu)-based preparative regimens in hematopoietic stem cell transplantation are commonly used. Previous studies have shown that Bu at a fixed dose of 3.2mg/kg/day (FBD) given intravenously decreases variability in drug pharmacokinetics and this decreases the dependency on therapeutic drug monitoring (TDM) of Bu. We compared the Bu dose given using TDM with the FBD of 3.2mg/kg/day. Seventy-three patients with acute leukemia, myelodysplasia, chronic myeloid leukemia, thalassemia major, and sickle cell disease were included. The mean age at transplant was 15years (range 2-55years) with 57% adults. Indication for transplantation was leukemia/myelodysplastic syndrome in 46% of the patients, while the remaining 54% were transplanted for inherited blood disorders. We found that the median FBD was lower than the median TDM dose by 39mg/day with a statistically significant difference (p<0.001) even after adjusting for the weight (median total FBD of 349mg, median TDM dose of 494mg, p<0.0001). Age and underlying condition (malignant vs. nonmalignant) were the main factors affecting Bu clearance (p<0.001 and p<0.07, respectively). TDM remains an important tool for the appropriate dosing of Bu in preparative regimens of hematopoietic stem cell transplantation, especially in populations with genetic admixture. Copyright © 2017 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.

  15. Flow Cytometry and Transplantation-Based Quantitative Assays for Satellite Cell Self-Renewal and Differentiation.

    PubMed

    Arpke, Robert W; Kyba, Michael

    2016-01-01

    In response to muscle damage, satellite cells proliferate and undertake both differentiation and self-renewal, generating new functional muscle tissue and repopulating this new muscle with stem cells for future injury responses. For many questions relating to the physiological regulation of satellite cells, quantitative readouts of self-renewal and differentiation can be very useful. There is a particular need for a quantitative assay for satellite cell self-renewal that does not rely solely upon sectioning, staining and counting cells in sections. In this chapter, we provide detailed methods for quantifying the self-renewal and differentiation potential of a given population of satellite cells using an assay involving transplantation into injured, regenerating muscle together with specific markers for donor cell identity and state of differentiation. In particular, using the Pax7-ZsGreen transgene as a marker of satellite cell state, self-renewal can be quantified by FACS on transplanted muscle to actually count the total number of resident satellite cells at time points following transplantation.

  16. Treosulfan-Based Conditioning Regimen in Sibling and Alternative Donor Hematopoietic Stem Cell Transplantation for Children with Sickle Cell Disease

    PubMed Central

    Marzollo, Antonio; Calore, Elisabetta; Tumino, Manuela; Pillon, Marta; Gazzola, Maria Vittoria; Destro, Roberta; Colombatti, Raffaella; Marson, Piero; Tison, Tiziana; Colpo, Anna; Mainardi, Chiara; Gabelli, Maria; Boaro, Maria Paola; Rossin, Sara; Strano, Aurora; Quaglia, Nadia; Menzato, Federica; Basso, Giuseppe; Sainati, Laura; Messina, Chiara

    2017-01-01

    Background and objectives Lack of suitable donors and regimen related toxicity are major barriers for hematopoietic stem cell transplantation (HSCT) in patients with sickle cell disease (SCD). The aim of the study is the assessment of efficacy and toxicity of Treosulfan-based conditioning regimen for SCD also when alternative donors such as mismatched unrelated donor and haploidentical donor are employed. Methods We report our single-center experience: 11 patients with SCD received HSCT with a Treosulfan/Thiotepa/Fludarabine/Anti-thymoglobulin conditioning regimen between 2010 and 2015. The donor was a matched sibling donor (n= 7), a haploidentical parent (n= 2), a matched unrelated donor (n= 1) or a mismatched unrelated donor (n=1). The haploidentical and mismatched unrelated donor grafts were manipulated by removing TCRαβ and CD19 positive cells. Results All patients survived the procedure and achieved stable engraftment. Stable mixed chimerism was observed in 5/11 patients. Grade III–IV regimen related toxicity was limited to mucositis and no grade III–IV graft-versus-host disease (GvHD) occurred. No SCD manifestation was observed post transplant and cerebral vasculopathy improved in 3/5 evaluable patients. Organ function evaluation showed no pulmonary, cardiac or renal toxicity but gonadal failure occurred in 1/4 evaluable patients. Conclusion Our data suggest that Treosulfan is associated with low toxicity and may be employed also for unrelated and haploidentical donor HSCT. PMID:28293402

  17. Cell sheet transplantation for heart tissue repair.

    PubMed

    Matsuura, Katsuhisa; Haraguchi, Yuji; Shimizu, Tatsuya; Okano, Teruo

    2013-08-10

    Cell transplantation is attracting considerable attention as the next-generation therapy for treatment of cardiovascular diseases. We have developed cell sheet engineering as a type of scaffold-less tissue engineering for application in myocardial tissue engineering and the repair of injured heart tissue by cell transplantation. Various types of cell sheet transplantation have improved cardiac function in animal models and clinical settings. Furthermore, cell-based tissue engineering with human induced pluripotent stem cell technology is about to create thick vascularized cardiac tissue for cardiac grafts and heart tissue models. In this review, we summarize the current cardiac cell therapies for treating heart failure with cell sheet technology and cell sheet-based tissue engineering.

  18. Palifermin is efficacious in recipients of TBI-based but not chemotherapy-based allogeneic hematopoietic stem cell transplants

    PubMed Central

    Goldberg, Jenna D.; Zheng, Junting; Castro-Malaspina, Hugo; Jakubowski, Ann A.; Heller, Glenn; van den Brink, Marcel R.M.; Perales, Miguel-Angel

    2014-01-01

    Palifermin, a recombinant human keratinocyte growth factor, is commonly given to prevent mucositis following autologous transplantation. In the allogeneic hematopoietic stem cell transplant (allo-HSCT) setting, safety and efficacy data are limited. We performed a retrospective study in 251 patients undergoing allo-HSCT, 154 of whom received peritransplant palifermin. In all patients, palifermin significantly decreased the mean number of days of total parenteral nutrition (TPN, 13 vs 16, p=0.006) and patient-controlled analgesia (PCA, 6 vs 10, p=0.023), and the length of initial hospital stay (LOS, 32 days vs 37 days, p=0.014). However, the effect of palifermin was only significant in patients who received a TBI but not busulfan-based chemotherapy conditioning regimen. In TBI recipients, palifermin decreased the mean number of days of TPN (13 vs 17, p<0.001) and PCA (7 vs 12, p=0.033), and the length of stay (32 days vs 38 days, p=0.001). Palifermin did not affect graft-versus-host disease, graft failure, or relapse. Therefore, in the largest analysis with this patient population to date, we demonstrate that palifermin is safe in allo-HSCT patients, decreases TPN and PCA use and decreases LOS following TBI-based but not chemotherapy-based allo-HSCT. PMID:22750997

  19. Total Body Irradiation-Based Myeloablative Haploidentical Stem Cell Transplantation Is a Safe and Effective Alternative to Unrelated Donor Transplantation in Patients Without Matched Sibling Donors.

    PubMed

    Solomon, Scott R; Sizemore, Connie A; Sanacore, Melissa; Zhang, Xu; Brown, Stacey; Holland, H Kent; Morris, Lawrence E; Bashey, Asad

    2015-07-01

    We enrolled 30 patients on a prospective phase II trial utilizing a total body irradiation (TBI)-based myeloablative preparative regimen (fludarabine 30 mg/m2/day × 3 days and TBI 150 cGy twice per day on day -4 to -1 [total dose 1200 cGy]) followed by infusion of unmanipulated peripheral blood stem cells from a haploidentical family donor (haplo). Postgrafting immunosuppression consisted of cyclophosphamide 50 mg/kg/day on days 3 and 4, mycophenolate mofetil through day 35, and tacrolimus through day 180. Median patient age was 46.5 years (range, 24 to 60). Transplantation diagnosis included acute myelogenous leukemia (n = 16), acute lymphoblastic leukemia (n = 6), chronic myelogenous leukemia (n = 5), myelodysplastic syndrome (n = 1), and non-Hodgkin's lymphoma (n = 2). Using the Dana Farber/Center for International Blood and Marrow Transplant Research/Disease Risk Index (DRI), patients were classified as low (n = 4), intermediate (n = 12), high (n = 11), and very high (n = 3) risk. All patients engrafted with a median time to neutrophil and platelet recovery of 16 and 25 days, respectively. All evaluable patients achieved sustained complete donor T cell and myeloid chimerism by day +30. Acute graft-versus-host disease (GVHD) grades II to IV and III and IV was seen in 43% and 23%, respectively. The cumulative incidence of chronic GVHD was 56% (severe in 10%). After a median follow-up of 24 months, the estimated 2-year overall survival (OS), disease-free survival (DFS), nonrelapse mortality, and relapse rate were 78%, 73%, 3%, and 24%, respectively. Two-year DFS and relapse rate in patients with low/intermediate risk disease was 100% and 0%, respectively, compared with 39% and 53% for patients with high/very high risk disease. When compared with a contemporaneously treated cohort of patients at our institution receiving myeloablative HLA-matched unrelated donor (MUD) transplantation (acute myelogenous leukemia [n = 17], acute lymphoblastic leukemia [n = 15

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

    USDA-ARS?s Scientific Manuscript database

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

  1. Transplantation of neural stem cells, Schwann cells and olfactory ensheathing cells for spinal cord injury : A Web of Science-based literature analysis.

    PubMed

    Zhang, Xing; Yin, Fei; Guo, Li; Zhao, Dongxu; Gong, Gu; Gao, Lei; Zhu, Qingsan

    2012-12-15

    To identify global research trends in transplantation of neural stem cells, Schwann cells and olfactory ensheathing cells for spinal cord injury. We performed a bibliometric analysis of studies on transplantation of neural stem cells, Schwann cells and olfactory ensheathing cells for spinal cord injury published from 2002 to 2011 and retrieved from the Web of Science, using the key words spinal cord injury along with either neural stem cell, Schwann cell or olfactory ensheathing cell. (a) peer-reviewed published articles on neural stem cells, Schwann cells or olfactory ensheathing cells for spinal cord injury indexed in the Web of Science; (b) original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial materials and news items; and (c) published between 2002 and 2011. (a) articles that required manual searching or telephone access; (b) documents that were not published in the public domain; and (c) corrected papers. (1) Annual publication output, distribution by journal, distribution by institution and top-cited articles on neural stem cells; (2) annual publication output, distribution by journal, distribution by institution and top-cited articles on Schwann cells; (3) annual publication output, distribution by journal, distribution by institution and top-cited articles on olfactory ensheathing cells. This analysis, based on articles indexed in the Web of Science, identified several research trends among studies published over the past 10 years in transplantation of neural stem cells, Schwann cells and olfactory ensheathing cells for spinal cord injury. The number of publications increased over the 10-year period examined. Most papers appeared in journals with a focus on neurology, such as Journal of Neurotrauma, Experimental Neurology and Glia. Research institutes publishing on the use of neural stem cells to repair spinal cord injury were mostly in the USA and Canada. Those publishing on the use of Schwann cells were

  2. Nanovector-based prolyl hydroxylase domain 2 silencing system enhances the efficiency of stem cell transplantation for infarcted myocardium repair

    PubMed Central

    Zhu, Kai; Lai, Hao; Guo, Changfa; Li, Jun; Wang, Yulin; Wang, Lingyan; Wang, Chunsheng

    2014-01-01

    Mesenchymal stem cell (MSC) transplantation has attracted much attention in myocardial infarction therapy. One of the limitations is the poor survival of grafted cells in the ischemic microenvironment. Small interfering RNA-mediated prolyl hydroxylase domain protein 2 (PHD2) silencing in MSCs holds tremendous potential to enhance their survival and paracrine effect after transplantation. However, an efficient and biocompatible PHD2 silencing system for clinical application is lacking. Herein, we developed a novel PHD2 silencing system based on arginine-terminated generation 4 poly(amidoamine) (Arg-G4) nanoparticles. The system exhibited effective and biocompatible small interfering RNA delivery and PHD2 silencing in MSCs in vitro. After genetically modified MSC transplantation in myocardial infarction models, MSC survival and paracrine function of IGF-1 were enhanced significantly in vivo. As a result, we observed decreased cardiomyocyte apoptosis, scar size, and interstitial fibrosis, and increased angiogenesis in the diseased myocardium, which ultimately attenuated ventricular remodeling and improved heart function. This work demonstrated that an Arg-G4 nanovector-based PHD2 silencing system could enhance the efficiency of MSC transplantation for infarcted myocardium repair. PMID:25429216

  3. Two complementary strategies to improve cell engraftment in mesenchymal stem cell-based therapy: Increasing transplanted cell resistance and increasing tissue receptivity.

    PubMed

    Ezquer, Fernando E; Ezquer, Marcelo E; Vicencio, Jose M; Calligaris, Sebastián D

    2017-01-02

    Over the past 2 decades, therapies based on mesenchymal stem cells (MSC) have been tested to treat several types of diseases in clinical studies, due to their potential for tissue repair and regeneration. Currently, MSC-based therapy is considered a biologically safe procedure, with the therapeutic results being very promising. However, the benefits of these therapies are not stable in the long term, and the final outcomes manifest with high inter-patient variability. The major cause of these therapeutic limitations results from the poor engraftment of the transplanted cells. Researchers have developed separate strategies to improve MSC engraftment. One strategy aims at increasing the survival of the transplanted MSCs in the recipient tissue, rendering them more resistant to the hostile microenvironment (cell-preconditioning). Another strategy aims at making the damaged tissue more receptive to the transplanted cells, favoring their interactions (tissue-preconditioning). In this review, we summarize several approaches using these strategies, providing an integral and updated view of the recent developments in MSC-based therapies. In addition, we propose that the combined use of these different conditioning strategies could accelerate the process to translate experimental evidences from pre-clinic studies to the daily clinical practice.

  4. Two complementary strategies to improve cell engraftment in mesenchymal stem cell-based therapy: Increasing transplanted cell resistance and increasing tissue receptivity

    PubMed Central

    Ezquer, Fernando E.; Ezquer, Marcelo E.; Vicencio, Jose M.; Calligaris, Sebastián D.

    2017-01-01

    ABSTRACT Over the past 2 decades, therapies based on mesenchymal stem cells (MSC) have been tested to treat several types of diseases in clinical studies, due to their potential for tissue repair and regeneration. Currently, MSC-based therapy is considered a biologically safe procedure, with the therapeutic results being very promising. However, the benefits of these therapies are not stable in the long term, and the final outcomes manifest with high inter-patient variability. The major cause of these therapeutic limitations results from the poor engraftment of the transplanted cells. Researchers have developed separate strategies to improve MSC engraftment. One strategy aims at increasing the survival of the transplanted MSCs in the recipient tissue, rendering them more resistant to the hostile microenvironment (cell-preconditioning). Another strategy aims at making the damaged tissue more receptive to the transplanted cells, favoring their interactions (tissue-preconditioning). In this review, we summarize several approaches using these strategies, providing an integral and updated view of the recent developments in MSC-based therapies. In addition, we propose that the combined use of these different conditioning strategies could accelerate the process to translate experimental evidences from pre-clinic studies to the daily clinical practice. PMID:27294313

  5. Narrative Based Medicine as a tool for needs assessment of patients undergoing hematopoietic stem cell transplantation.

    PubMed

    Gargiulo, Gianpaolo; Sansone, Vincenza; Rea, Teresa; Artioli, Giovanna; Botti, Stefano; Continisio, Grazia Isabella; Ferri, Paola; Masi, Daniela; Risitano, Antonio Maria; Simeone, Silvio; La Sala, Rachele

    2017-03-14

    In the last years we have seen an ever increasing number of patients with haematologic disorders who need hematopoietic stem cell transplantation (HSCT). The whole sector of HSCT results, infact to be in a continous scientific and technological clinical progress, offering a very advanced care. Despite this, some aspects are underconsidered, some of which could be fundamental to determine the success of the care pathway, such as the experience of the illness by the patient. Using a Narrative Based Medicine approach we wanted to investigate clinical, psychosocial and organizational aspects of the patient's journey whilst undergoing HSCT. Various narrative interviews were conducted using non-structured approach. Results were analysed by thematic contents. Psycological dimension is the most compromised: above all emerged sentiments of oppression linked to the isolation period in the Low Bacterial Load (LBL) room. To note are also the different dynamics with which the patients perceive the organisation and hospital structures, and how much these factors can influence their care experience. Results suggest the need in clinical practice of an integration between qualitative and clinical approach, so as to permit the psychosocial and relational necessities to emerge, often unexpressed by patients undergoing HSCT.

  6. Difficult Decisions: Fetal Cell Transplants.

    ERIC Educational Resources Information Center

    Slesnick, Irwin L.; Parakh, Jal S.

    1990-01-01

    Background information, techniques used, and details of the issues involved in the controversial issue of fetal cell transplantation are discussed. Questions for use in class discussion are provided. Suggestions for beginning a discussion are provided with accompanying questions. (CW)

  7. Concise Review: Mechanisms Behind Apoptotic Cell-Based Therapies Against Transplant Rejection and Graft versus Host Disease.

    PubMed

    Morelli, Adrian E; Larregina, Adriana T

    2016-05-01

    The main limitations to the success of transplantation are the antigraft response developed by the recipient immune system, and the adverse side effects of chronic immunosuppression. Graft-versus-host disease (GVHD) triggered by donor-derived T lymphocytes against the recipient tissues is another serious obstacle in the field of hematopoietic stem cell transplantation. Several laboratories have tested the possibility of promoting antigen (Ag)-specific tolerance for therapy of graft rejection, GVHD, and autoimmune disorders, by developing methodologies that mimic the mechanisms by which the immune system maintains peripheral tolerance in the steady state. It has been long recognized that the silent clearance of cells undergoing apoptosis exerts potent immune-regulatory effects and provides apoptotic cell-derived Ags to those Ag-presenting cells (APCs) that internalize them, in particular macrophages and dendritic cells. Therefore, in situ-targeting of recipient APCs by systemic administration of leukocytes in early apoptosis and bearing donor Ags represents a relatively simple approach to control the antidonor response against allografts. Here, we review the mechanisms by which apoptotic cells are silently cleared by phagocytes, and how such phenomenon leads to down-regulation of the innate and adaptive immunity. We discuss the evolution of apoptotic cell-based therapies from murine models of organ/tissue transplantation and GVHD, to clinical trials. We make emphasis on potential limitations and areas of concern of apoptotic cell-based therapies, and on how other immune-suppressive therapies used in the clinics or tested experimentally likely also function through the silent clearance of apoptotic cells by the immune system. Stem Cells 2016;34:1142-1150.

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

    PubMed

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

    2010-03-01

    Hepatic cell transplantation consists of grafting already differentiated cells such as hepatocytes. Human hepatocytes are viable and functionally active. Liver cell transplantation is carried out by means of a 3-step method: isolation of hepatocytes from donor liver rejected for orthotopic transplantation, preparing a cell suspension for infusion and, finally, hepatocytes are implanted into the recipient. There are established protocols for the isolation of human hepatocytes from unused segments of donor livers, based on collagenase digestion of cannulated liver tissue at 37 degrees C. The hepatocytes can be used fresh or cryopreserved. Cryopreservation of isolated human hepatocytes would then be available for planned use. In cell transplant, the important aspects are: infusion route, number of cells, number of infusions and viability of the cells. The cells are infused into the patient through a catheter inserted via portal vein or splenic artery. Liver cell transplantation allows liver tissue to be used that would, otherwise, be discarded, enabling multiple patients to be treated with hepatocytes from a single tissue donor. Copyright 2009 AEC. Published by Elsevier Espana. All rights reserved.

  9. L-asparaginase-based regimens followed by allogeneic hematopoietic stem cell transplantation improve outcomes in aggressive natural killer cell leukemia.

    PubMed

    Jung, Ki Sun; Cho, Su-Hee; Kim, Seok Jin; Ko, Young Hyeh; Kang, Eun-Suk; Kim, Won Seog

    2016-04-18

    Aggressive nature killer cell leukemia (ANKL) is a mature NK-T cell lymphoma with worse prognosis, but optimal treatment is unclear. Therefore, we analyzed the efficacy of L-asparaginase-based regimens for ANKL patients. Twenty-one patients who received dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) or etoposide, ifosfamide, dexamethasone, and L-asparaginase (VIDL) chemotherapy at Samsung Medical Center were selected. The overall response rate for all patients was 33% (7/21); 38% (5/13) in SMILE and 40% (2/5) in VIDL, respectively. The median progression-free survival was 3.9 months (95% CI 0.0-8.1 months) and median overall survival was 7.0 months (95% CI 2.3-11.7 months). Treatment response (P = 0.001), hematopoietic stem cell transplantation (HSCT) (P = 0.007) and negative conversion of Epstein-Barr virus (EBV) DNA titer after treatment (P = 0.004) were significantly associated with survival. Thus, L-asparaginase-based regimens followed by allogeneic HSCT seem to improve the outcome for ANKL patients.

  10. Cardiomyopathy in patients after posttransplant cyclophosphamide-based hematopoietic cell transplantation.

    PubMed

    Lin, Chien-Jung; Vader, Justin M; Slade, Michael; DiPersio, John F; Westervelt, Peter; Romee, Rizwan

    2017-05-15

    The use of posttransplant cyclophosphamide (PT-Cy) has contributed significantly to the success of haploidentical hematopoietic cell transplantation (HCT). Furthermore, several studies have shown promising results in the human leukocyte antigen-matched setting. However, the use of high-dose cyclophosphamide has been associated with the development of cardiomyopathy. There is a paucity of data concerning posttransplant cardiac complications in patients undergoing PT-Cy-based HCT. A retrospective analysis of 176 patients undergoing HCT with PT-Cy was performed. The overall survival, left ventricular ejection fractions, brain natriuretic peptide levels, and cardiac comorbidities were reviewed. The associations between comorbidities and the onset of heart failure were assessed with a Cox proportional hazards model. Pretransplant cardiomyopathy was found in 16 patients (9.1%) but had no effect on their posttransplant overall survival. Thirty-five patients (21.9%) developed posttransplant cardiomyopathy, which correlated with increased mortality, but this was not statistically different from the frequency-matched non-PT-Cy cohort. The majority of these cardiomyopathies occurred in the setting of an infectious milieu. An age greater than 60 years and an HCT comorbidity index score equal to or greater than 4 were the only risk factors that correlated with posttransplant cardiomyopathy. The presence of pretransplant cardiomyopathy does not negatively affect overall survival for patients who undergo HCT with PT-Cy. Furthermore, cardiomyopathy in PT-Cy patients is not caused by PT-Cy but is mostly concurrent with infectious complications and is associated with reduced overall survival. Traditional cardiovascular risk factors do not fully predict the occurrence of posttransplant cardiomyopathy. Future research is required to unravel predictive factors for cardiomyopathy after PT-Cy-based HCT. Cancer 2017;123:1800-1809. © 2017 American Cancer Society. © 2017 American Cancer

  11. Oral candidiasis in hematopoietic cell transplantation patients: an outcome-based analysis.

    PubMed

    Epstein, Joel B; Hancock, Pamela J; Nantel, Stephen

    2003-08-01

    Despite aggressive antifungal prophylaxis, the increased risk for systemic fungal infection in recipients of hematopoietic cell transplants (HCT) continues to be a significant concern because Candida infection can cause morbidity and mortality in these patients. The objectives of this study were to examine the relationship of oral colonization by Candida species to systemic infection, mortality, and the impact of antifungal treatment on a population of recipients of HCT. One hundred and fifteen consecutive patients undergoing hematopoietic cell transplantation were evaluated. Oral examinations and cultures for Candida were completed before transplantation and on a weekly basis until discharge. The oral complications were assessed, and the level of mucositis was scored by using the National Cancer Institute grade. Systemic antifungal prophylaxis was provided to all patients. Chlorhexidine oral rinses were also routinely provided. Colonization by Candida species was identified in 31% of patients. Fifty-six percent of patients with colonization had clinical evidence of oral candidiasis. Significantly decreased Candida colonization was seen in patients using chlorhexidine alone compared with those using chlorhexidine and nystatin together (P <.046). Twenty-five patients died in the immediate posttransplantation period, 17 of whom were Candida-positive. The length of hospital stay ranged from 15 to 153 days; increased stay was also associated with Candida colonization (P =.04). Seventy-four percent of all patients developed ulcerative mucositis. More severe mucositis was seen in patients undergoing chemotherapy and radiation therapy. There was no significant difference between Candida colonization and the presence or severity of mucositis. Despite systemic and topical antifungal prophylaxis, oropharyngeal colonization by Candida species was common in patients who had received HCT. Candidiasis was commonly present in those who did not survive the early transplant period

  12. Haplotype-based banking of human pluripotent stem cells for transplantation: potential and limitations.

    PubMed

    Zimmermann, Anna; Preynat-Seauve, Olivier; Tiercy, Jean-Marie; Krause, Karl-Heinz; Villard, Jean

    2012-09-01

    High expectations surround the area of stem cells therapeutics. However, the cells' source-adult or embryonic-and the cells' origin-patient-derived autologous or healthy donor genetically unrelated-remain subjects of debate. Autologous origins have the advantage of a theoretical absence of immune rejection by the recipient. However, this approach has several limitations with regard to the disease of the recipient and to potential problems with the generation, expansion, and manipulation of autologous induced pluripotent stem cells (iPS cells) preparation. An alternative to using autologous cells is the establishment of a bank of well-characterized adult cells that would be used to generate iPS cells and their derivatives. In the context of transplantation, such cells would come from genetically unrelated donors and the immune system of the recipient would reject the graft without immunosuppressive therapy. To minimize the risk of rejection, human leukocyte antigen (HLA) compatibility is certainly the best option, and the establishment of an HLA-organized bank would mean having a limited number of stem cells that would be sufficient for a large number of recipients. The concept of haplobanking with HLA homozygous cell lines would also limit the number of HLA mismatches, but such an approach will not necessarily be less immunogenic in terms of selection criteria, because of the limited number of HLA-compatible loci and the level of HLA typing resolution.

  13. Treosulfan-based conditioning regimen for allogeneic haematopoietic stem cell transplantation in children with sickle cell disease.

    PubMed

    Strocchio, Luisa; Zecca, Marco; Comoli, Patrizia; Mina, Tommaso; Giorgiani, Giovanna; Giraldi, Eugenia; Vinti, Luciana; Merli, Pietro; Regazzi, Mario; Locatelli, Franco

    2015-06-01

    Although allogeneic haematopoietic stem cell transplantation (HSCT) still represents the only consolidated possibility of cure for sickle cell disease (SCD) patients, its use has been limited by the risk of morbidity and mortality associated with conventional myeloablative therapy. The introduction of treosulfan to replace busulfan in conditioning regimens has recently been explored by virtue of its lower toxicity profile. We report our experience with a treosulfan/thiotepa/fludarabine conditioning for human leucocyte antigen (HLA)-matched sibling or unrelated donor-HSCT in 15 children with SCD, and compare patient outcomes with those of a historical cohort (15 patients) given a busulfan-based regimen. Engraftment was achieved in 28 out of 30 patients (93%), with one case of graft failure in either group. The conditioning regimen was well tolerated in both groups, with no cases of grade III-IV regimen-related toxicity. The 7-year overall survival (OS) and disease-free survival (DFS) for the whole cohort were 100% and 93%, respectively, with a 93% DFS in both busulfan and treosulfan groups. No SCD-related adverse events occurred after engraftment in patients with complete or mixed donor chimerism. This retrospective analysis suggests that a treosulfan-based conditioning regimen is able to ensure engraftment with excellent OS/DFS and low regimen-related toxicity in patients with SCD. © 2015 John Wiley & Sons Ltd.

  14. Accessory cells for β-cell transplantation.

    PubMed

    Staels, W; De Groef, S; Heremans, Y; Coppens, V; Van Gassen, N; Leuckx, G; Van de Casteele, M; Van Riet, I; Luttun, A; Heimberg, H; De Leu, N

    2016-02-01

    Despite recent advances, insulin therapy remains a treatment, not a cure, for diabetes mellitus with persistent risk of glycaemic alterations and life-threatening complications. Restoration of the endogenous β-cell mass through regeneration or transplantation offers an attractive alternative. Unfortunately, signals that drive β-cell regeneration remain enigmatic and β-cell replacement therapy still faces major hurdles that prevent its widespread application. Co-transplantation of accessory non-islet cells with islet cells has been shown to improve the outcome of experimental islet transplantation. This review will highlight current travails in β-cell therapy and focuses on the potential benefits of accessory cells for islet transplantation in diabetes.

  15. Allogeneic transplantation strategies including haploidentical transplantation in sickle cell disease.

    PubMed

    Gluckman, Eliane

    2013-01-01

    Sickle cell disease (SCD) is the most common inherited hemoglobinopathy. Despite antenatal counseling and neonatal screening programs implemented in higher income countries, SCD is still associated with multiple morbidities and early mortality. To date, the only curative approach to SCD is hematopoietic stem cell transplantation, but this therapy is not yet established worldwide. The registries of the European Blood and Marrow Transplant (EBMT) and the Centre for International Blood and Marrow Transplant Research (CIBMTR) account, respectively, for 611 and 627 patients receiving transplantations for SCD. Most of these patients were transplanted with grafts from an HLA-identical sibling donor. The main obstacles to increasing the number of transplantations are a lack of awareness on the part of physicians and families, the absence of reliable prognostic factors for severity, and the perceived risk that transplantation complications may outweigh the benefits of early transplantation. Results show that more than 90% of patients having undergone an HLA-identical sibling transplantation after myeloablative conditioning are cured, with very limited complications. Major improvement is expected from the use of new reduced-toxicity conditioning regimens and the use of alternative donors, including unrelated cord blood transplantations and related haploidentical bone marrow or peripheral blood stem cell transplantations.

  16. Reduction of Relapse after Unrelated Donor Stem Cell Transplantation by KIR-Based Graft Selection

    PubMed Central

    Heidenreich, Silke; Kröger, Nicolaus

    2017-01-01

    Besides donor T cells, natural killer (NK) cells are considered to have a major role in preventing relapse after allogeneic hematopoietic stem cell transplantation (HSCT). After T-cell-depleted haploidentical HSCT, a strong NK alloreactivity has been described. These effects have been attributed to killer-cell immunoglobulin-like receptors (KIR). Abundant reports suggest a major role of KIR not only on outcome after haploidentical HSCT but also in the unrelated donor setting. In this review, we give a brief overview of the mechanism of NK cell activation, nomenclature of KIR haplotypes, human leukocyte antigen (HLA) groups, and distinct models for prediction of NK cell alloreactivity. It can be concluded that KIR-ligand mismatch seems to provoke adverse effects in unrelated donor HSCT with reduced overall survival and increased risk for high-grade acute graft-versus-host disease. The presence of activating KIR, as seen in KIR haplotype B, as well as the patient’s HLA C1/x haplotype might reduce relapse in myeloid malignancies. PMID:28228753

  17. Reduction of Relapse after Unrelated Donor Stem Cell Transplantation by KIR-Based Graft Selection.

    PubMed

    Heidenreich, Silke; Kröger, Nicolaus

    2017-01-01

    Besides donor T cells, natural killer (NK) cells are considered to have a major role in preventing relapse after allogeneic hematopoietic stem cell transplantation (HSCT). After T-cell-depleted haploidentical HSCT, a strong NK alloreactivity has been described. These effects have been attributed to killer-cell immunoglobulin-like receptors (KIR). Abundant reports suggest a major role of KIR not only on outcome after haploidentical HSCT but also in the unrelated donor setting. In this review, we give a brief overview of the mechanism of NK cell activation, nomenclature of KIR haplotypes, human leukocyte antigen (HLA) groups, and distinct models for prediction of NK cell alloreactivity. It can be concluded that KIR-ligand mismatch seems to provoke adverse effects in unrelated donor HSCT with reduced overall survival and increased risk for high-grade acute graft-versus-host disease. The presence of activating KIR, as seen in KIR haplotype B, as well as the patient's HLA C1/x haplotype might reduce relapse in myeloid malignancies.

  18. Stem Cell Transplant Patients and Fungal Infections

    MedlinePlus

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

  19. High incidence of post-transplant cytomegalovirus reactivations in myeloma patients undergoing autologous stem cell transplantation after treatment with bortezomib-based regimens: a survey from the Rome transplant network.

    PubMed

    Marchesi, F; Mengarelli, A; Giannotti, F; Tendas, A; Anaclerico, B; Porrini, R; Picardi, A; Cerchiara, E; Dentamaro, T; Chierichini, A; Romeo, A; Cudillo, L; Montefusco, E; Tirindelli, M C; De Fabritiis, P; Annino, L; Petti, M C; Monarca, B; Arcese, W; Avvisati, G

    2014-02-01

    The incidence of cytomegalovirus (CMV) reactivations in patients with multiple myeloma (MM) receiving autologous stem cell transplantation (ASCT) is relatively low. However, the recent increased use of novel agents, such as bortezomib and/or immunomodulators, before transplant, has led to an increasing incidence of Herpesviridae family virus infections. The aim of the study was to establish the incidence of post-engraftment symptomatic CMV reactivations in MM patients receiving ASCT, and to compare this incidence with that of patients treated with novel agents or with conventional chemotherapy before transplant. The study was a survey of 80 consecutive patients who underwent ASCT after treatment with novel agents (Group A). These patients were compared with a cohort of 89 patients treated with VAD regimen (vincristine, doxorubicin, and dexamethasone) before ASCT (Group B). Overall, 7 patients (4.1%) received an antiviral treatment for a symptomatic CMV reactivation and 1 died. The incidence of CMV reactivations was significantly higher in Group A than in Group B (7.5% vs. 1.1%; P = 0.048). When compared with Group B, the CMV reactivations observed in Group A were significantly more frequent in patients who received bortezomib, whether or not associated with immunomodulators (9.4% vs. 1.1%; P = 0.019), but not in those treated with immunomodulators only (3.7% vs. 1.1%; P = 0.396). These results suggest that MM patients treated with bortezomib-based regimens are at higher risk of developing a symptomatic CMV reactivation after ASCT.

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

    PubMed

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

    2015-01-01

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

  1. Memory B cells in Transplantation

    PubMed Central

    Chong, Anita S.; Sciammas, Roger

    2014-01-01

    Much of the research on the humoral response to allografts has focused on circulating serum antibodies and the long-lived plasma cells that produce these antibodies. In contrast, the interrogation of the quiescent memory B cell compartment is technically more challenging and thus has not been incorporated into the clinical diagnostic or prognostic toolkit. In this review, we discuss new technologies that have allowed this heretofore enigmatic subset of B cells to be identified at quiescence and during a recall response. These technologies in experimental models are providing new insights into memory B cell heterogeneity with respect to their phenotype, cellular function and the antibodies they produce. Similar technologies are also allowing for the identification of comparable memory alloreactive B cells in transplant recipients. While much of the focus in transplant immunology has been on controlling the alloreactive B cell population, long-term transplant patient survival is critically dependent on protection by pathogen-specific memory B cells. Techniques are also available that allow the interrogation of memory B cell response to pathogen re-encounter. Thus we are poised in our ability toinvestigate how immunosuppression affects allo- as well as pathogen-specific memory B cells, and reason that these investigation can yield new insights that will be beneficial for graft as well as patient survival. PMID:25525921

  2. Pre- and postmortem imaging of transplanted cells

    PubMed Central

    Andrzejewska, Anna; Nowakowski, Adam; Janowski, Miroslaw; Bulte, Jeff WM; Gilad, Assaf A; Walczak, Piotr; Lukomska, Barbara

    2015-01-01

    Therapeutic interventions based on the transplantation of stem and progenitor cells have garnered increasing interest. This interest is fueled by successful preclinical studies for indications in many diseases, including the cardiovascular, central nervous, and musculoskeletal system. Further progress in this field is contingent upon access to techniques that facilitate an unambiguous identification and characterization of grafted cells. Such methods are invaluable for optimization of cell delivery, improvement of cell survival, and assessment of the functional integration of grafted cells. Following is a focused overview of the currently available cell detection and tracking methodologies that covers the entire spectrum from pre- to postmortem cell identification. PMID:26366076

  3. Organ or Stem Cell Transplant and Your Mouth

    MedlinePlus

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

  4. Stem-cell-activated organ following ultrasound exposure: better transplant option for organ transplantation.

    PubMed

    Wang, Sen; Li, Yu; Ji, Ying-Chang; Lin, Chang-Min; Man, Cheng; Zheng, Xiao-Xuan

    2010-01-01

    Although doctors try their best to protect transplants during surgery, there remain great challenges for the higher survival rate and less rejection of transplants after organ transplantation. Growing evidence indicates that the stem cells could function after injury rather than aging, implying that suitable injury may activate the stem cells of damaged organs. Furthermore, it has been revealed that stem cells can be used to induce tolerance in transplantation and the ultrasound has great biological effects on organs. Basing on these facts, we hypothesize that the stem cells within the transplants can be activated by ultrasound with high-frequency and medium-intensity. Therefore, the stem-cell-activated organs (SCAO) can be derived, and the SCAO will be better transplant option for organ transplantation. We postulate the ultrasound can change the molecular activity and/or quantity of the stem cells, the membrane permeability, the cell-cell junctions, and their surrounding microenvironments. As a result, the stem cells are activated, and the SCAO will acquire more regenerative capacity and less rejection. In the paper, we also discuss the process, methods and models for verifying the theory, and the consequences. We believe the theory may provide a practical method for the clinical application of the ultrasound and stem cells in organ transplantation.

  5. Impaired interferon-alpha production by plasmacytoid dendritic cells after cord blood transplantation in children: implication for post-transplantation toll-like receptor ligand-based immunotherapy.

    PubMed

    Charrier, Emily; Cordeiro, Paulo; Brito, Rose-Marie; Harnois, Michaël; Mezziani, Samira; Herblot, Sabine; Le Deist, Françoise; Duval, Michel

    2014-10-01

    Plasmacytoid dendritic cells (pDCs) initiate both innate and adaptive immune responses, making them attractive targets for post-transplantation immunotherapy, particularly after cord blood transplantation (CBT). Toll-like receptor (TLR) agonists are currently studied for pDC stimulation in various clinical settings. Their efficacy depends on pDC number and functionality, which are unknown after CBT. We performed a longitudinal study of pDC reconstitution in children who underwent bone marrow transplantation (BMT) and single-unit CBT. Both CBT and unrelated BMT patients received antithymocyte globulin as part of their graft-versus-host disease prophylaxis regimen. pDC blood counts were higher in CBT patients than in healthy volunteers from 2 to 9 months after transplantation, whereas they remained lower in BMT patients. We showed that cord blood progenitors gave rise in vitro to a 500-fold increase in functional pDCs over bone marrow counterparts. Upon stimulation with a TLR agonist, pDCs from both CBT and BMT recipients upregulated T cell costimulatory molecules, whereas interferon-alpha (IFN-α) production was impaired for 9 months after CBT. TLR agonist treatment is thus not expected to induce IFN-α production by pDCs after CBT, limiting its immunotherapeutic potential. Fortunately, in vitro production of large amounts of functional pDCs from cord blood progenitors paves the way for the post-transplantation adoptive transfer of pDCs. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  6. Transcatheter based electromechanical mapping guided intramyocardial transplantation and in vivo tracking of human stem cell based three dimensional microtissues in the porcine heart.

    PubMed

    Emmert, Maximilian Y; Wolint, Petra; Winklhofer, Sebastian; Stolzmann, Paul; Cesarovic, Nikola; Fleischmann, Thea; Nguyen, Thi D L; Frauenfelder, Thomas; Böni, Roland; Scherman, Jacques; Bettex, Dominique; Grünenfelder, Jürg; Schwartlander, Ruth; Vogel, Viola; Gyöngyösi, Mariann; Alkadhi, Hatem; Falk, Volkmar; Hoerstrup, Simon P

    2013-03-01

    Stem cells have been repeatedly suggested for cardiac regeneration after myocardial infarction (MI). However, the low retention rate of single cell suspensions limits the efficacy of current therapy concepts so far. Taking advantage of three dimensional (3D) cellular self-assembly prior to transplantation may be beneficial to overcome these limitations. In this pilot study we investigate the principal feasibility of intramyocardial delivery of in-vitro generated stem cell-based 3D microtissues (3D-MTs) in a porcine model. 3D-MTs were generated from iron-oxide (MPIO) labeled human adipose-tissue derived mesenchymal stem cells (ATMSCs) using a modified hanging-drop method. Nine pigs (33 ± 2 kg) comprising seven healthy ones and two with chronic MI in the left ventricle (LV) anterior wall were included. The pigs underwent intramyocardial transplantation of 16 × 10(3) 3D-MTs (1250 cells/MT; accounting for 2 × 10(7) single ATMSCs) into the anterior wall of the healthy pigs (n = 7)/the MI border zone of the infarcted (n = 2) of the LV using a 3D NOGA electromechanical mapping guided, transcatheter based approach. Clinical follow-up (FU) was performed for up to five weeks and in-vivo cell-tracking was performed using serial magnet resonance imaging (MRI). Thereafter, the hearts were harvested and assessed by PCR and immunohistochemistry. Intramyocardial transplantation of human ATMSC based 3D-MTs was successful in eight animals (88.8%) while one pig (without MI) died during the electromechanical mapping due to sudden cardiac-arrest. During FU, no arrhythmogenic, embolic or neurological events occurred in the treated pigs. Serial MRI confirmed the intramyocardial presence of the 3D-MTs by detection of the intracellular iron-oxide MPIOs during FU. Intramyocardial retention of 3D-MTs was confirmed by PCR analysis and was further verified on histology and immunohistochemical analysis. The 3D-MTs appeared to be viable, integrated and showed an intact micro architecture. We

  7. Stem cell transplantation for autoimmune diseases.

    PubMed

    Gratwohl, A; Passweg, J; Gerber, I; Tyndall, A

    2001-12-01

    Much progress has been made in the field of haemopoietic stem cell transplants (HSCTs) for severe autoimmune disorders. Theoretical considerations, animal data and anecdotal evidence suggested some time ago that intensive immunoablation followed by autologous HSCT could restore normal immune reactivity in patients with severe autoimmune disorders. Based on a concept statement issued in 1995, two European societies, the European League Against Rheumatism (EULAR) and the European Group for Blood and Marrow Transplantation (EBMT) began collecting phase I/II trial data in an international collaborative network. Sufficient information from more than 350 patients allows a preliminary assessment with level three evidence. Autologous HSCTs can induce remissions in all disease categories tested so far. Remissions can be transient or durable. HSCTs are associated with significant morbidity and mortality. Treatment-related mortality (TRM) is near 10% at 1 year and is associated with the intensity of the conditioning and the stage of the disease at the time of transplant. Marked interdisease differences exist. There are few data available in haematological autoimmune diseases, more in systemic sclerosis (SSc), systemic lupus erythematosus (SLE), juvenile idiopathic arthritis (JIA) and multiple sclerosis (MS). Patient selection has been recognized as a crucial element from the phase I-II trials. Patients with advanced disease, severely compromised organ function or irreversible organ damage should not be considered as candidates for HSCT. Prospective randomized studies should now determine the value of HSCT compared to standard therapy. Such trials are ongoing for patients with systemic sclerosis (ASTIS trial--Autologous Stem Cell Transplantation International Scleroderma Trial) or are planned for patients with multiple sclerosis (ASTIMS trial--Autologous Stem Cell Transplantation International Multiple Sclerosis Trial) and rheumatoid arthritis (ASTIRA trial--Autologous Stem

  8. New culture medium concepts for cell transplantation.

    PubMed

    Lee, S; Kim, B Y; Yeo, J E; Nemeno, J G; Jo, Y H; Yang, W; Nam, B M; Namoto, S; Tanaka, S; Sato, M; Lee, K M; Hwang, H S; Lee, J I

    2013-10-01

    Before cell or tissue transplantation, cells or tissues have to be maintained for a certain period in vitro using culture medium and methods. Most culture media contain substances such as pH indicators and buffers. It is not known whether some of these substances are safe for subsequent application in the transplantation of cells or tissues into the human body. We investigated culture media and methods with respect to the safety of the components in future transplantation applications. A modified culture medium--medical fluid-based culture medium (FCM)--was designed by using various fluids and injectable drugs that are already currently permitted for use in clinical medicine. Medium components necessary for optimal cell growth were obtained from approved drugs. FCM was manufactured with adjusted final concentrations of the medium components similar to those in commercial Dulbecco's modified Eagle's medium (DMEM). In particular, 1029.40 mg/L amino acids, approximately 88.85 mg/L vitamins, 13,525.77 mg/L inorganic salts, and 4500 mg/L D-glucose comprise the high-glucose FCM. Next, human fat synovium-derived mesenchymal stem cells and rat H9c2 (2-1) cells were cultured under 2 conditions: (1) DMEM-high glucose (HG), an original commercial medium, and (2) optimized FCM-HG. We assessed the morphologies and proliferation rates of these cells. We observed that FCM-HG was able to induce the growth of FS-MSC and commercially available H9c2 cell. The morphologies and proliferation patterns of these cells cultured under FCM-HG showed no differences compared with cells grown in DMEM-HG. Our data suggest that FCM, which we developed for the first time according to the concept of drug repositioning, was a useful culture medium, especially in cultured cells intended for human cell transplantation. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

  9. Personalized Home-based Interval Exercise Training May Improve Cardiorespiratory Fitness in Cancer Patients Preparing to Undergo Hematopoietic Cell Transplantation

    PubMed Central

    Wood, William A; Phillips, Brett; Smith-Ryan, Abbie E; Wilson, Doug; Deal, Allison M; Bailey, Charlotte; Meeneghan, Mathew; Reeve, Bryce B; Basch, Ethan M; Bennett, Antonia V; Shea, Thomas C; Battaglini, Claudio L

    2016-01-01

    Impaired cardiorespiratory fitness is associated with inferior survival in patients preparing to undergo hematopoietic cell transplantation (HCT). Exercise training based on short, higher-intensity intervals has the potential to efficiently improve cardiorespiratory fitness. We studied home-based interval exercise training (IET) in 40 patients prior to autologous (N=20) or allogeneic (N=20) HCT. Each session consisted of 5, three-minute intervals of walking, jogging, or cycling at 65-95% maximal heart rate (MHR) with 3 minutes of low intensity exercise (<65% MHR) between intervals. Participants were asked to perform sessions at least 3 times weekly. The duration of the intervention was at least 6 weeks, depending on each patient’s scheduled transplantation date. Cardiorespiratory fitness was assessed from a peak oxygen consumption test (VO2peak) and a 6 minute walk (6MWD) before and after the intervention period. For the autologous HCT cohort, improvements in VO2peak (p=0.12) and 6MWD (p=0.19) were not statistically significant. For the allogeneic cohort, the median VO2peak improvement was 3.7ml/kg*min (p=0.005) and the median 6MWD improvement was 34 meters (p=0.006). Home-based, interval exercise training can be performed prior to HCT and has the potential to improve cardiorespiratory fitness. PMID:26999467

  10. Periodontal tissue regeneration by transplantation of rat adipose-derived stromal cells in combination with PLGA-based solid scaffolds.

    PubMed

    Akita, Daisuke; Morokuma, Masakazu; Saito, Yoko; Yamanaka, Katsuyuki; Akiyama, Yuko; Sato, Momoko; Mashimo, Takayuki; Toriumi, Taku; Arai, Yoshinori; Kaneko, Tadashi; Tsukimura, Naoki; Isokawa, Keitaro; Ishigami, Tomohiko; Honda, Masaki J

    2014-01-01

    Regeneration of damaged periodontium is challenging due to its multi-tissue composition. Mesenchymalstem cell-based approaches using adipose-derived stromal cells (ASCs) may contribute to periodontal reconstruction, particularly when combined with the use of scaffolds to maintain a space for new tissue growth. The aim of this study was to assess the regenerative potential of ASCs derived from inbred or outbred rats in combination with novel solid scaffolds composed of PLGA (Poly D,L-lactic-co-glycolic acid) (PLGA-scaffolds). Cultured ASCs seeded onto PLGA scaffolds (ASCs/PLGA) or PLGA-scaffolds (PLGA) alone were transplanted into periodontal fenestration defects created in F344 or Sprague Dawley (SD) rats. Micro-CT analysis showed a significantly higher percentage of bone growth in the ASCs/PLGA groups compared with the PLGA-alone groups at five weeks after surgery. Similarly, histomorphometric analysis demonstrated thicker growth of periodontal ligament and cementum layers in the ASCs/PLGA-groups compared with the PLGA-alone groups. In addition, transplanted DiI-labeled ASCs were observed in the periodontal regenerative sites. The present investigation demonstrated the marked ability of ASCs in combination with PLGA scaffolds to repair periodontal defects.

  11. [Tolerance in transplantation: potential contribution of haematopoietic transplantation and cell therapy].

    PubMed

    Kleinclauss, François; Bittard, Hugues; Perruche, Sylvain; de Carvalho-Bittencourt, Marcello; Chalopin, Jean-Marc; Hervé, Patrick; Tiberghien, Pierre; Saas, Philippe

    2003-12-01

    The ultimate objective of organ transplantation is to obtain a state of tolerance, i.e. long-term acceptance of the graft without immunosuppressive therapy in order to limit the complications of these treatments (viral infections, tumours, etc.). The various immunological mechanisms allowing a state of tolerance will be described in this review. Among these various experimental strategies, combined bone marrow (or haematopoietic stem cell) transplantation and organ transplantation, made possible by the development of non-myeloablative or less intensive conditioning, appears to be one of the most promising lines of research. This approach leads to colonization of the recipient by donor cells. This state is described as "macro-chimerism" and achieves a real state of central tolerance in relation to an organ derived from the bone marrow donor. We have shown recently that intravenous injection of apoptotic cells in combination with allogeneic bone marrow cells increases the success rate of bone marrow transplantation. In a model of combined bone marrow/solid organ transplantation, these apoptotic cells induce tolerance limited to the donor's bone marrow cell antigens without inducing auto-immunization. We therefore propose a new approach to cell-based therapy (using the immunomodulating properties of apoptotic cells) to promote the success of haematopoietic stem cell transplantation. This approach can be particularly useful in combined haematopoietic stem cell and organ transplantation in order to induce a state of macro-chimerism.

  12. [Transplantation of corneal endothelial cells].

    PubMed

    Amano, Shiro

    2002-12-01

    Though conventional corneal transplantation has achieved great success, it still has several drawbacks including limited availability of donor corneas, recurrent allograft rejection, and subsequent graft failure in certain cases. Reconstructing clinically usable corneas by applying the technology of regenerative medicine can offer a solution to these problems, as well as making corneal transplantation a non-emergency surgery and enabling the usage of banked corneal cells. In the present study, we focused on corneal endothelium that is critical for corneal transparency and investigated the reconstruction of cornea utilizing cultured human corneal endothelial cells (HCECs). We succeeded in steadily culturing HCECs by using culture dishes pre-coated with extracellular matrix produced by calf corneal endothelial cells and culture media that contained basic fibroblast growth factor and fetal bovine serum. We performed the following analysis utilizing these cultured HCECs. The older the donor was, the more frequently large senescent cells appeared in the passaged HCECs. The telomeres of HCECs were measured as terminal restriction fragments (TRF) by Southern blotting. HCECs, in vivo from donors in their seventies had a long TRFs of over 12 kilobases. Passaging shortened the TRFs but there was no difference in TRFs among donors of various ages. These results indicated that shortening of telomere length is not related to senescence of HCECs. We investigated the role of advanced glycation end products (AGEs) in the senescence of in vivo HCECs. The results indicated that AGE-protein in the aqueous humor is endocytosed into HCECs via AGE receptors expressed on the surface of HCECs and damages HCECs by producing reactive oxygen species and inducing apoptosis, suggesting that AGEs, at least partly, cause the senescence of HECEs. HCECs were cultured using adult human serum instead of bovine serum to get rid of bovine material that can be infected with prions. Primary and passage

  13. Process-Based Expansion and Neural Differentiation of Human Pluripotent Stem Cells for Transplantation and Disease Modeling

    PubMed Central

    Stover, Alexander E.; Brick, David J.; Nethercott, Hubert E.; Banuelos, Maria G.; Sun, Lei; O’Dowd, Diane K.; Schwartz, Philip H.

    2014-01-01

    Robust strategies for developing patient-specific, human, induced pluripotent stem cell (iPSC)-based therapies of the brain require an ability to derive large numbers of highly defined neural cells. Recent progress in iPSC culture techniques includes partial-to-complete elimination of feeder layers, use of defined media, and single-cell passaging. However, these techniques still require embryoid body formation or coculture for differentiation into neural stem cells (NSCs). In addition, none of the published methodologies has employed all of the advances in a single culture system. Here we describe a reliable method for long-term, single-cell passaging of PSCs using a feeder-free, defined culture system that produces confluent, adherent PSCs that can be differentiated into NSCs. To provide a basis for robust quality control, we have devised a system of cellular nomenclature that describes an accurate genotype and phenotype of the cells at specific stages in the process. We demonstrate that this protocol allows for the efficient, large-scale, cGMP-compliant production of transplantable NSCs from all lines tested. We also show that NSCs generated from iPSCs produced with the process described are capable of forming both glia defined by their expression of S100β and neurons that fire repetitive action potentials. PMID:23893392

  14. Cryptococcosis in solid-organ, hematopoietic stem cell, and tissue transplant recipients: evidence-based evolving trends.

    PubMed

    Sun, Hsin-Yun; Wagener, Marilyn M; Singh, Nina

    2009-06-01

    The impact of current transplantation practices on the characteristics of cryptococcosis in solid-organ transplant recipients is not well defined. The incidence of cryptococcal disease among solid-organ transplant recipients has remained unchanged; however, patients are less likely to present with central nervous system or disseminated disease and are more likely to have cryptococcosis limited to the lungs. Additionally, lipid formulations of amphotericin B are now used more frequently, whereas their use in combination with flucytosine has decreased. The overall mortality of cryptococcosis has significantly improved in the current era. Renal failure remains associated with poor outcome, whereas use of lipid formulations of amphotericin B is associated with a higher survival rate. Despite rare infectious complication, certain peculiar attributes of cryptococcal disease in hematopoietic stem cell recipients and tissue transplant recipients warrant recognition.

  15. T Regulatory Cells and Transplantation Tolerance

    PubMed Central

    Gorantla, Vijay S.; Schneeberger, Stefan; Brandacher, Gerald; Sucher, Robert; Zhang, Dong; Lee, Andrew; Zheng, Xin Xiao

    2010-01-01

    Despite the development of successful immunosuppression protocols and tremendous improvement in short-term graft survival rates, the problem of chronic graft loss remains the bane of clinical transplantation. The induction and maintenance of transplantation tolerance is the “Holy grail” of transplantation. The recent identification and characterization of regulatory T cells (T regs) has opened up exciting opportunities for tolerance induction, immunotherapy and immunomodulation in transplantation. This review focuses on current understanding of regulatory T cells and their role in transplantation tolerance. PMID:20541385

  16. Mantle cell lymphoma: observation to transplantation

    PubMed Central

    Sweetenham, John W.

    2015-01-01

    Mantle cell lymphoma as a rare non-Hodgkin B-cell lymphoma can present in different clinical presentations such as an aggressive form or a more indolent picture. Treatment modality is based on multiple factors including age, presence or absence of symptoms, and comorbidities. Watchful waiting is a reasonable approach for asymptomatic patients especially in elderly. In symptomatic patients, treatment is chemo-immunotherapy followed by maintenance immunotherapy or autologous bone marrow transplant. Allogeneic bone marrow transplant has a potential benefit of cure for relapsed/refractory cases, but it has a high mortality rate. Novel treatment with agents such as ibrutinib, a Bruton tyrosine kinase inhibitor, has shown promising results in relapse/refractory cases. We extensively review the most recent data on diagnostic and therapeutic management of mantle cell lymphoma through presenting two extreme clinical scenarios. PMID:25642314

  17. Mantle cell lymphoma: observation to transplantation.

    PubMed

    Rajabi, Babak; Sweetenham, John W

    2015-02-01

    Mantle cell lymphoma as a rare non-Hodgkin B-cell lymphoma can present in different clinical presentations such as an aggressive form or a more indolent picture. Treatment modality is based on multiple factors including age, presence or absence of symptoms, and comorbidities. Watchful waiting is a reasonable approach for asymptomatic patients especially in elderly. In symptomatic patients, treatment is chemo-immunotherapy followed by maintenance immunotherapy or autologous bone marrow transplant. Allogeneic bone marrow transplant has a potential benefit of cure for relapsed/refractory cases, but it has a high mortality rate. Novel treatment with agents such as ibrutinib, a Bruton tyrosine kinase inhibitor, has shown promising results in relapse/refractory cases. We extensively review the most recent data on diagnostic and therapeutic management of mantle cell lymphoma through presenting two extreme clinical scenarios.

  18. Pharmacokinetics-based optimal dose prediction of donor source-dependent response to mycophenolate mofetil in unrelated hematopoietic cell transplantation.

    PubMed

    Wakahashi, Kanako; Yamamori, Motohiro; Minagawa, Kentaro; Ishii, Shinichi; Nishikawa, Shinichirou; Shimoyama, Manabu; Kawano, Hiroki; Kawano, Yuko; Kawamori, Yuriko; Sada, Akiko; Matsui, Toshimitsu; Katayama, Yoshio

    2011-08-01

    Mycophenolate mofetil (MMF) has been widely used for prophylaxis against graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation (allo-SCT). However, no clear advantage over methotrexate has been reported, other than reduced incidence of mucositis. We speculated that the wide inter-individual variation of plasma mycophenolic acid (MPA) levels veiled the benefits of MMF. Data from 36 unrelated allogeneic bone marrow (allo-BMT) and cord blood transplantation (CBT) were analyzed retrospectively based on MPA area under the curve (AUC(0-24h)). In allo-BMT, high AUC(0-24h) (>30 μg h/ml) resulted in no incidence of grade II-IV acute/extensive chronic GVHD and tended to show higher overall and disease-free survival, lower relapse rates, and non-relapse mortality. In CBT, AUC(0-24h) less than 30 μg h/ml was sufficient for low incidence of acute/chronic GVHD and high survival. Strong correlation between AUC(0-24h) and C(2h), plasma MPA concentration at 2 h after administration was observed. Single point assessment of C(2h) was shown to provide a useful surrogate of AUC(0-24h) to predict GVHD incidence. The results of this study suggest that individualized MMF dosing in a donor source-dependent fashion may be important for maximizing the benefit of MMF in allo-SCT.

  19. Cost of Stem Cell-Based Tissue-Engineered Airway Transplants in the United Kingdom: Case Series

    PubMed Central

    Culme-Seymour, Emily J.; Mason, Katrina; Vallejo-Torres, Laura; Carvalho, Carla; Partington, Leanne; Crowley, Claire; Hamilton, Nick J.; Toll, Ed C.; Butler, Colin R.; Elliott, Martin J.; Birchall, Martin A.; Lowdell, Mark W.

    2016-01-01

    Stem cell-based tissue-engineered tracheas are at an early stage in their product development cycle. Tens of patients have been treated worldwide in predominantly compassionate use settings, demonstrating significant promise. This potentially life-saving treatment is complex, and the cost and its implications for such treatments are yet to be fully understood. The costs are compounded by varying strategies for graft preparation and transplant, resulting in differing clinical and laboratory costs from different research groups. In this study, we present a detailed breakdown of the clinical and manufacturing costs for three of the United Kingdom (UK) patients treated with such transplants. All three patients were treated under Compassionate Use legislation, within the UK National Health Service (NHS) hospital setting. The total costs for the three UK patients treated ranged from $174,420 to $740,500. All three patients were in a state of poor health at time of treatment and had a number of complexities in addition to the restricted airway. This is the first time a cost analysis has been made for a tissue-engineered organ and provides a benchmark for future studies, as well as comparative data for use in reimbursement considerations. PMID:26559535

  20. Treosulfan-Based Conditioning and Hematopoietic Cell Transplantation for Nonmalignant Diseases: A Prospective Multi-Center Trial

    PubMed Central

    Burroughs, Lauri M.; Nemecek, Eneida R.; Torgerson, Troy R.; Storer, Barry E.; Talano, Julie-An; Domm, Jennifer; Giller, Roger H.; Shimamura, Akiko; Delaney, Colleen; Skoda-Smith, Suzanne; Thakar, Monica S.; Baker, K. Scott; Rawlings, David J.; Englund, Janet A.; Flowers, Mary E. D.; Deeg, H. Joachim; Storb, Rainer; Woolfrey, Ann E.

    2015-01-01

    Hematopoietic cell transplantation (HCT) is effective in the treatment of patients with nonmalignant diseases and for many is the only known cure. Conventional myeloablative regimens have been associated with unacceptably high early transplant-related mortality (TRM) particularly in patients with co-morbid conditions. This prospective multicenter trial was designed to determine the safety and engraftment efficacy of treosulfan-based conditioning in patients with nonmalignant diseases. Thirty-one patients received HLA-matched related (n=4) or unrelated (n=27) grafts following conditioning with treosulfan (total dose: 42 g/m2), fludarabine (total dose: 150 mg/m2), ± thymoglobulin (6 mg/kg; n=22). Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus and methotrexate. All patients engrafted. Day-100 TRM was 0%. With a median follow-up of 2 years, the 2-year survival was 90%. Three patients died of GVHD, recurrent hemophagocytic lymphohistiocytosis, and a surgical complication, respectively. The cumulative incidences of grades II–IV and III–IV acute GVHD at day 100 and chronic GVHD at 2 years were 62%, 10% and 21%, respectively. Patients who received thymoglobulin had a significantly lower incidence of grade III-IV acute GVHD (0% versus 33%; P = 0.005). These results indicate that the combination of treosulfan, fludarabine, and thymoglobulin is effective at establishing donor engraftment with low toxicity and improved survival in patients with nonmalignant diseases, and support the need for future disease-specific clinical trials. PMID:25196857

  1. Prophylactic and therapeutic adenoviral vector-based multivirus-specific T-cell immunotherapy for transplant patients

    PubMed Central

    Dasari, Vijayendra; Schuessler, Andrea; Smith, Corey; Wong, Yide; Miles, John J; Smyth, Mark J; Ambalathingal, George; Francis, Ross; Campbell, Scott; Chambers, Daniel; Khanna, Rajiv

    2016-01-01

    Viral infections including cytomegalovirus, Epstein-Barr virus, adenovirus, and BK virus are a common and predictable problem in transplant recipients. While cellular immune therapies have been successfully used to tackle infectious complications in transplant recipients, manufacturing immunotherapies to address the multitude of possible pathogens can be technically challenging and labor-intensive. Here we describe a novel adenoviral antigen presentation platform (Ad-MvP) as a tool for rapid generation of multivirus-specific T-cells in a single step. Ad-MvP encodes 32 CD8+ T-cell epitopes from cytomegalovirus, Epstein-Barr virus, adenovirus, and BK virus as a contiguous polyepitope. We demonstrate that Ad-MvP vector can be successfully used for rapid in vitro expansion of multivirus-specific T-cells from transplant recipients and in vivo priming of antiviral T-cell immunity. Most importantly, using an in vivo murine model of Epstein-Barr virus-induced lymphoma, we also show that adoptive immunotherapy with Ad-MvP expanded autologous and allogeneic multivirus-specific T-cells is highly effective in controlling Epstein-Barr virus tumor outgrowth and improving overall survival. We propose that Ad-MvP has wide ranging therapeutic applications in greatly facilitating in vivo priming of antiviral T-cells, the generation of third-party T-cell banks as “off-the-shelf” therapeutics as well as autologous T-cell therapies for transplant patients. PMID:27606351

  2. The effect of a polyurethane-based reverse thermal gel on bone marrow stromal cell transplant survival and spinal cord repair.

    PubMed

    Ritfeld, Gaby J; Rauck, Britta M; Novosat, Tabitha L; Park, Daewon; Patel, Pavan; Roos, Raymund A C; Wang, Yadong; Oudega, Martin

    2014-02-01

    Cell therapy for nervous tissue repair is limited by low transplant survival. We investigated the effects of a polyurethane-based reverse thermal gel, poly(ethylene glycol)-poly(serinol hexamethylene urethane) (ESHU) on bone marrow stromal cell (BMSC) transplant survival and repair using a rat model of spinal cord contusion. Transplantation of BMSCs in ESHU at three days post-contusion resulted in a 3.5-fold increase in BMSC survival at one week post-injury and a 66% increase in spared nervous tissue volume at four weeks post-injury. These improvements were accompanied by enhanced hindlimb motor and sensorimotor recovery. In vitro, we found that ESHU protected BMSCs from hydrogen peroxide-mediated death, resulting in a four-fold increase in BMSC survival with two-fold fewer BMSCs expressing the apoptosis marker, caspase 3 and the DNA oxidation marker, 8-oxo-deoxyguanosine. We argue that ESHU protected BMSCs transplanted is a spinal cord contusion from death thereby augmenting their effects on neuroprotection leading to improved behavioral restoration. The data show that the repair effects of intraneural BMSC transplants depend on the degree of their survival and may have a widespread impact on cell-based regenerative medicine.

  3. Hematopoietic cell transplantation in Latin America.

    PubMed

    Eckrich, Michael; Pasquini, Marcelo

    2012-04-01

    The first bone marrow transplantation in Latin America was performed more than 30 years ago and since then several countries have started transplant programs. The Center for International Blood and Marrow Transplant Research captured information on 13,473 transplants performed in Latin America from 1981 to 2009. The current report summarizes this activity. Argentina, Mexico, and Brazil have the largest activity in the region. Despite increase in the annual number of transplants, the activity is limited to sibling donor and autologous transplants. Indications are similar to other regions with a proportionally higher number of pediatric transplants for treatment of non-malignant diseases. Unrelated donor transplant activity is also increasing through collaborations with international donor registries and the development of the first national donor registry in Brazil. Umbilical cord transplants were also reported in Latin American centers, mainly in Brazil and most commonly used for treatment of children with malignant diseases. In conclusion, hematopoietic cell transplantation is routinely performed in several centers in Latin America. However, the activity is low compared to the population in need. Challenges with costs of transplantation, donor availability, number of centers of excellence, and trained personnel need to be addressed for further development of this field in the region. Additionally, more integration between countries and transplant centers is an important next step and can assist in improving awareness for the field and maximizing the transplant activity in Latin America.

  4. High-Dose CD20-Targeted Radioimmunotherapy-Based Autologous Transplantation Improves Outcomes for Persistent Mantle Cell Lymphoma

    PubMed Central

    Cassaday, Ryan D.; Stevenson, Philip A.; Gooley, Theodore A.; Chauncey, Thomas R.; Pagel, John M.; Rajendran, Joseph; Till, Brian G.; Philip, Mary; Orozco, Johnnie J.; Bensinger, William I.; Holmberg, Leona A.; Shustov, Andrei R.; Green, Damian J.; Smith, Stephen D.; Libby, Edward N.; Maloney, David G.; Press, Oliver W.; Gopal, Ajay K.

    2015-01-01

    SUMMARY Autologous stem cell transplant (ASCT) can improve outcomes for mantle cell lymphoma (MCL) patients, yet relapses are frequent. We hypothesized that high-dose anti-CD20 radioimmunotherapy (RIT)-based conditioning could improve results in this setting. We thus assessed 162 consecutive patients with MCL at our centre undergoing ASCT following high-dose RIT-based (n = 61) or standard (n = 101) conditioning. RIT patients were less likely to be in first remission (48% vs 72%; p = 0.002), be in complete remission (CR) (26% vs 61%; p < 0.001) and have chemosensitive disease (84% vs 96%; p = 0.006). RIT-based conditioning was associated with a reduced risk of treatment failure (hazard ratio [HR] 0.40; p = 0.001) and mortality (HR 0.49; p = 0.01) after adjusting for these imbalances. This difference increased as disease status worsened (from CR to partial remission to stable/progressive disease), with respective HRs of 1.14, 0.53 and 0.04 for mortality, and 0.66, 0.36 and 0.14 for treatment failure. RIT-based conditioning appears to improve outcome following ASCT for MCL patients unable to achieve CR after controlling for imbalances in important risk factors. These data support the further study of RIT and radiation-based strategies in a risk-adapted approach to ASCT for persistent MCL. PMID:26455717

  5. Regulatory myeloid cells in transplantation.

    PubMed

    Rosborough, Brian R; Raïch-Regué, Dàlia; Turnquist, Heth R; Thomson, Angus W

    2014-02-27

    Regulatory myeloid cells (RMC) are emerging as novel targets for immunosuppressive (IS) agents and hold considerable promise as cellular therapeutic agents. Herein, we discuss the ability of regulatory macrophages, regulatory dendritic cells, and myeloid-derived suppressor cells to regulate alloimmunity, their potential as cellular therapeutic agents, and the IS agents that target their function. We consider protocols for the generation of RMC and the selection of donor- or recipient-derived cells for adoptive cell therapy. Additionally, the issues of cell trafficking and antigen (Ag) specificity after RMC transfer are discussed. Improved understanding of the immunobiology of these cells has increased the possibility of moving RMC into the clinic to reduce the burden of current IS agents and to promote Ag-specific tolerance. In the second half of this review, we discuss the influence of established and experimental IS agents on myeloid cell populations. IS agents believed historically to act primarily on T cell activation and proliferation are emerging as important regulators of RMC function. Better insights into the influence of IS agents on RMC will enhance our ability to develop cell therapy protocols to promote the function of these cells. Moreover, novel IS agents may be designed to target RMC in situ to promote Ag-specific immune regulation in transplantation and to usher in a new era of immune modulation exploiting cells of myeloid origin.

  6. Productivity loss due to premature mortality caused by blood cancer: a study based on patients undergoing stem cell transplantation.

    PubMed

    Ortega-Ortega, Marta; Oliva-Moreno, Juan; Jiménez-Aguilera, Juan de Dios; Romero-Aguilar, Antonio; Espigado-Tocino, Ildefonso

    2015-01-01

    Stem cell transplantation has been used for many years to treat haematological malignancies that could not be cured by other treatments. Despite this medical breakthrough, mortality rates remain high. Our purpose was to evaluate labour productivity losses associated with premature mortality due to blood cancer in recipients of stem cell transplantations. We collected primary data from the clinical histories of blood cancer patients who had undergone stem cell transplantation between 2006 and 2011 in two Spanish hospitals. We carried out a descriptive analysis and calculated the years of potential life lost and years of potential productive life lost. Labour productivity losses due to premature mortality were estimated using the Human Capital method. An alternative approach, the Friction Cost method, was used as part of the sensitivity analysis. Our findings suggest that, in a population of 179 transplanted and deceased patients, males and people who die between the ages of 30 and 49 years generate higher labour productivity losses. The estimated loss amounts to over €31.4 million using the Human Capital method (€480,152 using the Friction Cost method), which means an average of €185,855 per death. The highest labour productivity losses are produced by leukaemia. However, lymphoma generates the highest loss per death. Further efforts are needed to reduce premature mortality in blood cancer patients undergoing transplantations and reduce economic losses. Copyright © 2014 SESPAS. Published by Elsevier Espana. All rights reserved.

  7. Second Cancer Risk and Late Mortality in Adult Australians Receiving Allogeneic Hematopoietic Stem Cell Transplantation: A Population-Based Cohort Study.

    PubMed

    Vajdic, Claire M; Mayson, Eleni; Dodds, Anthony J; O'Brien, Tracey; Wilcox, Leonie; Nivison-Smith, Ian; Le Marsney, Renate; Daniels, Benjamin; Ashton, Lesley J

    2016-05-01

    We quantified the risk of second cancer and late mortality in a population-based Australian cohort of 3273 adult (≥15 years) allogeneic hematopoietic stem cell transplant recipients (1992 to 2007). Most recipients received nonradiation-based conditioning and a peripheral blood graft from a matched related donor. Using record linkage with death and cancer registries, 79 second cancers were identified a median of 3.5 years after transplantation. The competing-risk adjusted cumulative incidence of second cancers was 3.35% (95% CI, 2.59 to 4.24) at 10 years, and the cancer risk relative to the matched general population was 2.10 (95% CI, 1.65 to 2.56). We observed an excess risk of melanoma and lip, tongue, esophagus, and soft tissue cancers. Cancer risk relative to the general population was elevated for those transplanted for lymphoma, some leukemia subtypes, and severe aplastic anemia, recipients who developed chronic graft-versus-host disease (cGVHD) and irrespective of radiation-based conditioning or stem cell source. In those alive 2 years after transplantation (n = 1463), the cumulative incidence of late mortality was 22.2% (95% CI, 19.7 to 24.9) at 10 years, and the risk of death relative to the matched general population was 13.8 (95% CI, 12.2 to 15.6). In multivariable modeling, risk of late death was reduced for females compared with males and those transplanted for chronic myeloid leukemia compared with acute myeloid leukemia; risk was increased for recipients with discordant sex donors, cGVHD, those undergoing second transplants, and disease relapse. Adults undergoing allogeneic transplantation have unique cancer and mortality risk profiles that continue to warrant prevention and surveillance activities targeted at high-risk subgroups.

  8. T cell depleted haploidentical transplantation: positive selection.

    PubMed

    Aversa, Franco

    2011-06-22

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

  9. Thiotepa-based high-dose therapy for autologous stem cell transplantation in lymphoma: a retrospective study from the EBMT.

    PubMed

    Sellner, L; Boumendil, A; Finel, H; Choquet, S; de Rosa, G; Falzetti, F; Scime, R; Kobbe, G; Ferrara, F; Delmer, A; Sayer, H; Amorim, S; Bouabdallah, R; Finke, J; Salles, G; Yakoub-Agha, I; Faber, E; Nicolas-Virelizier, E; Facchini, L; Vallisa, D; Zuffa, E; Sureda, A; Dreger, P

    2016-02-01

    Clinical information about thiotepa-based autologous stem cell transplantation (auto-SCT) outside the primary central nervous system lymphoma (PCNSL) field is sparse. In this registry-based retrospective study, we evaluated potential risks and benefits of thiotepa-based preparative regimens compared with BEAM (carmustine, etoposide, cytarabine, melphalan) in auto-SCT for diffuse large B-cell lymphoma (DLBCL, excluding PCNSL), follicular lymphoma (FL) or Hodgkin lymphoma (HL). A total of 14 544 patients (589 thiotepa and 13 955 BEAM) met the eligibility criteria, and 535 thiotepa- and 1031 BEAM-treated patients were matched in a 1:2 ratio for final comparison. No significant differences between thiotepa and BEAM groups for any survival end point were identified in the whole sample or disease entity subsets. For a more detailed analysis, 47 TEAM (thiotepa, etoposide, cytarabine, melphalan)-treated patients were compared with 75 matched BEAM patients with additional collection of toxicity data. Again, there were no significant differences between the two groups for any survival end point. In addition, the frequency of common infectious and non-infectious complications including secondary malignancies was comparable between TEAM and BEAM. These results indicate that thiotepa-based high-dose therapy might be a valuable alternative to BEAM in DLBCL, HL and FL. Further evaluation by prospective clinical trials is warranted.

  10. Development and Implementation of an Internet-Based Survivorship Care Program for Cancer Survivors Treated with Hematopoietic Stem Cell Transplantation

    PubMed Central

    Syrjala, Karen L.; Stover, Allison C.; Yi, Jean C.; Artherholt, Samantha B.; Romano, Eleni M.; Schoch, Gary; Stewart, Susan; Flowers, Mary E.D.

    2011-01-01

    Introduction The internet provides a widely accessible modality for meeting survivorship care needs of cancer survivors. In this paper we describe the development and implementation of an internet site designed as a base from which to conduct a randomized controlled trial to meet psycho-educational needs of hematopoietic stem cell transplantation (HSCT) survivors. Methods A cross-disciplinary team designed, wrote content and programmed an internet site for online study registration, consent, assessment, and study implementation. All 3–18 year survivors of HSCT for hematologic malignancy treated at one transplant center were approached by mail for participation. All study activities could be conducted without study staff contact. However, participants had options for phone or email contact with study staff as desired. Results Of 1775 participants approached for the study, 775 (58% of those eligible) consented and completed baseline assessment. Mean age was 51.7 (SD=12.5, age range 18–79), with 56% male. 57% required staff contact one or more times; a majority were for minor technical issues or delays in completion of enrollment or baseline assessment. Discussions/Conclusions This study demonstrated the potential for providing internet-based survivorship care to long-term survivors of HSCT. Although building a survivorship internet site requires a team with diverse expertise, once built, these resources can be implemented rapidly with large numbers of survivors. Implications for Cancer Survivors While internet-based services will not meet all the needs of cancer survivors, this methodology represents an important modality for augmenting onsite clinical services as a method for meeting psycho-educational, information and resource needs of cancer survivors. PMID:21544671

  11. Development and implementation of an Internet-based survivorship care program for cancer survivors treated with hematopoietic stem cell transplantation.

    PubMed

    Syrjala, Karen L; Stover, Allison C; Yi, Jean C; Artherholt, Samantha B; Romano, Eleni M; Schoch, Gary; Stewart, Susan; Flowers, Mary E D

    2011-09-01

    The Internet provides a widely accessible modality for meeting survivorship care needs of cancer survivors. In this paper, we describe the development and implementation of an Internet site designed as a base from which to conduct a randomized controlled trial to meet psycho-educational needs of hematopoietic stem cell transplantation (HSCT) survivors. A cross-disciplinary team designed, wrote content, and programmed an Internet site for online study registration, consent, assessment, and study implementation. All survivors who were 3-18 years after HSCT for hematologic malignancy and treated at one transplant center were approached by mail for participation. All study activities could be conducted without study staff contact. However, participants had options for phone or email contact with study staff as desired. Of 1,775 participants approached for the study, 775 (58% of those eligible) consented and completed baseline assessment. Mean age was 51.7 (SD, 12.5; age range, 18-79 years), with 56% male. Fifty-seven percent required staff contact one or more times; a majority were for minor technical issues or delays in completion of enrollment or baseline assessment. This study demonstrated the potential for providing Internet-based survivorship care to long-term survivors of HSCT. Although building a survivorship Internet site requires a team with diverse expertise, once built, these resources can be implemented rapidly with large numbers of survivors. While Internet-based services will not meet all the needs of cancer survivors, this methodology represents an important modality for augmenting onsite clinical services as a method for meeting psycho-educational, information, and resource needs of cancer survivors.

  12. Sirolimus-based graft-versus-host disease prophylaxis promotes the in vivo expansion of regulatory T cells and permits peripheral blood stem cell transplantation from haploidentical donors.

    PubMed

    Peccatori, J; Forcina, A; Clerici, D; Crocchiolo, R; Vago, L; Stanghellini, M T L; Noviello, M; Messina, C; Crotta, A; Assanelli, A; Marktel, S; Olek, S; Mastaglio, S; Giglio, F; Crucitti, L; Lorusso, A; Guggiari, E; Lunghi, F; Carrabba, M; Tassara, M; Battaglia, M; Ferraro, A; Carbone, M R; Oliveira, G; Roncarolo, M G; Rossini, S; Bernardi, M; Corti, C; Marcatti, M; Patriarca, F; Zecca, M; Locatelli, F; Bordignon, C; Fleischhauer, K; Bondanza, A; Bonini, C; Ciceri, F

    2015-02-01

    Hematopoietic stem cell transplantation (HSCT) from human leukocyte antigen (HLA) haploidentical family donors is a promising therapeutic option for high-risk hematologic malignancies. Here we explored in 121 patients, mostly with advanced stage diseases, a sirolimus-based, calcineurin-inhibitor-free prophylaxis of graft-versus-host disease (GvHD) to allow the infusion of unmanipulated peripheral blood stem cell (PBSC) grafts from partially HLA-matched family donors (TrRaMM study, Eudract 2007-5477-54). Conditioning regimen was based on treosulfan and fludarabine, and GvHD prophylaxis on antithymocyte globulin Fresenius (ATG-F), rituximab and oral administration of sirolimus and mycophenolate. Neutrophil and platelet engraftment occurred in median at 17 and 19 days after HSCT, respectively, and full donor chimerism was documented in patients' bone marrow since the first post-transplant evaluation. T-cell immune reconstitution was rapid, and high frequencies of circulating functional T-regulatory cells (Treg) were documented during sirolimus prophylaxis. Incidence of acute GvHD grade II-IV was 35%, and occurrence and severity correlated negatively with Treg frequency. Chronic GvHD incidence was 47%. At 3 years after HSCT, transpant-related mortality was 31%, relapse incidence 48% and overall survival 25%. In conclusion, GvHD prophylaxis with sirolimus-mycophenolate-ATG-F-rituximab promotes a rapid immune reconstitution skewed toward Tregs, allowing the infusion of unmanipulated haploidentical PBSC grafts.

  13. Hepatocyte transplantation in children with liver cell failure

    PubMed Central

    Hamooda, Mohamed

    2016-01-01

    Patients with hepatic failure and liver-based metabolic disorders require management which is both costly and complex. Hepatocyte transplantation has been very encouraging as an alternative to organ transplantation for liver disease treatment, and studies in rodents, show that transplants involving isolated liver cells can reverse hepatic failure, and correct various metabolic deficiencies of the liver. This 2016 review is based on a literature search using PubMed including original articles, reviews, cases and clinical guidelines. The search terms were “hepatocyte transplantation”, “liver transplantation”, “liver cell failure”, “metabolic liver disorders”, “orthotropic liver transplantation”, “hepatocytes” and “stem cell transplantation”. The goal of this review is to summarize the significance of hepatocyte transplantation, the sources of hepatocytes and the barriers of hepatocyte transplantation using a detailed review of literature. Our review shows that treatment of patients with liver disease by hepatocyte transplantation has expanded exponentially, especially for patients suffering from liver-based metabolic disorders. Once hepatocyte transplantation has been shown to effectively replace organ transplantation for a portion of patients with life-threatening liver metabolic diseases and those with liver failure it will make cell therapy effective and available for a broad population of patients with liver disorders. PMID:27957309

  14. Biosimilar G-CSF based mobilization of peripheral blood hematopoietic stem cells for autologous and allogeneic stem cell transplantation.

    PubMed

    Schmitt, Michael; Publicover, Amy; Orchard, Kim H; Görlach, Matthias; Wang, Lei; Schmitt, Anita; Mani, Jiju; Tsirigotis, Panagiotis; Kuriakose, Reeba; Nagler, Arnon

    2014-01-01

    The use of granulocyte colony stimulating factor (G-CSF) biosimilars for peripheral blood hematopoietic stem cell (PBSC) mobilization has stimulated an ongoing debate regarding their efficacy and safety. However, the use of biosimilar G-CSF was approved by the European Medicines Agency (EMA) for all the registered indications of the originator G-CSF (Neupogen (®) ) including mobilization of stem cells. Here, we performed a comprehensive review of published reports on the use of biosimilar G-CSF covering patients with hematological malignancies as well as healthy donors that underwent stem cell mobilization at multiple centers using site-specific non-randomized regimens with a biosimilar G-CSF in the autologous and allogeneic setting. A total of 904 patients mostly with hematological malignancies as well as healthy donors underwent successful autologous or allogeneic stem cell mobilization, respectively, using a biosimilar G-CSF (520 with Ratiograstim®/Tevagrastim, 384 with Zarzio®). The indication for stem cell mobilization in hematology patients included 326 patients with multiple myeloma, 273 with Non-Hodgkin's lymphoma (NHL), 79 with Hodgkin's lymphoma (HL), and other disease. 156 sibling or volunteer unrelated donors were mobilized using biosimilar G-CSF. Mobilization resulted in good mobilization of CD34+ stem cells with side effects similar to originator G-CSF. Post transplantation engraftment did not significantly differ from results previously documented with the originator G-CSF. The side effects experienced by the patients or donors mobilized by biosimilar G-CSF were minimal and were comparable to those of originator G-CSF. In summary, the efficacy of biosimilar G-CSFs in terms of PBSC yield as well as their toxicity profile are equivalent to historical data with the reference G-CSF.

  15. Solid cancers after allogeneic hematopoietic cell transplantation

    PubMed Central

    Curtis, Rochelle E.; Socié, Gérard; Sobocinski, Kathleen A.; Gilbert, Ethel; Landgren, Ola; Travis, Lois B.; Travis, William D.; Flowers, Mary E. D.; Friedman, Debra L.; Horowitz, Mary M.; Wingard, John R.; Deeg, H. Joachim

    2009-01-01

    Transplant recipients have been reported to have an increased risk of solid cancers but most studies are small and have limited ability to evaluate the interaction of host, disease, and treatment-related factors. In the largest study to date to evaluate risk factors for solid cancers, we studied a multi-institutional cohort of 28 874 allogeneic transplant recipients with 189 solid malignancies. Overall, patients developed new solid cancers at twice the rate expected based on general population rates (observed-to-expected ratio 2.1; 95% confidence interval 1.8-2.5), with the risk increasing over time (P trend < .001); the risk reached 3-fold among patients followed for 15 years or more after transplantation. New findings showed that the risk of developing a non–squamous cell carcinoma (non-SCC) following conditioning radiation was highly dependent on age at exposure. Among patients irradiated at ages under 30 years, the relative risk of non-SCC was 9 times that of nonirradiated patients, while the comparable risk for older patients was 1.1 (P interaction < .01). Chronic graft-versus-host disease and male sex were the main determinants for risk of SCC. These data indicate that allogeneic transplant survivors, particularly those irradiated at young ages, face increased risks of solid cancers, supporting strategies to promote lifelong surveillance among these patients. PMID:18971419

  16. Solid cancers after allogeneic hematopoietic cell transplantation.

    PubMed

    Rizzo, J Douglas; Curtis, Rochelle E; Socié, Gérard; Sobocinski, Kathleen A; Gilbert, Ethel; Landgren, Ola; Travis, Lois B; Travis, William D; Flowers, Mary E D; Friedman, Debra L; Horowitz, Mary M; Wingard, John R; Deeg, H Joachim

    2009-01-29

    Transplant recipients have been reported to have an increased risk of solid cancers but most studies are small and have limited ability to evaluate the interaction of host, disease, and treatment-related factors. In the largest study to date to evaluate risk factors for solid cancers, we studied a multi-institutional cohort of 28 874 allogeneic transplant recipients with 189 solid malignancies. Overall, patients developed new solid cancers at twice the rate expected based on general population rates (observed-to-expected ratio 2.1; 95% confidence interval 1.8-2.5), with the risk increasing over time (P trend < .001); the risk reached 3-fold among patients followed for 15 years or more after transplantation. New findings showed that the risk of developing a non-squamous cell carcinoma (non-SCC) following conditioning radiation was highly dependent on age at exposure. Among patients irradiated at ages under 30 years, the relative risk of non-SCC was 9 times that of nonirradiated patients, while the comparable risk for older patients was 1.1 (P interaction < .01). Chronic graft-versus-host disease and male sex were the main determinants for risk of SCC. These data indicate that allogeneic transplant survivors, particularly those irradiated at young ages, face increased risks of solid cancers, supporting strategies to promote lifelong surveillance among these patients.

  17. Haematopoietic Cell Transplants in Latin America

    PubMed Central

    Gale, Robert Peter; Seber, Adriana; Bonfim, Carmem; Pasquini, Marcello

    2016-01-01

    Haematopoietic cell transplants are done by more than 1500 transplant centres in 75 countries, mostly for life-threatening haematological disorders. However, transplant technology and access are not uniformly-distributed worldwide. Most transplants are done in predominately Europe, North America and some Asian countries. We review transplants activity in Latin America, a geographic region with a population of more than 600 million persons living in countries with diverse economic and social development levels. The data indicate a 20-40-fold lower frequency of transplants in Latin America compared with Europe and North America. We show that although economics, infrastructure and expertise are important limitations, other variables also operate. Changes in several of these variables may substantially increase transplant activity in Latin America. PMID:26999468

  18. Haematopoietic cell transplants in Latin America.

    PubMed

    Gale, R P; Seber, A; Bonfim, C; Pasquini, M

    2016-07-01

    Haematopoietic cell transplants are done by more than 1500 transplant centres in 75 countries, mostly for life-threatening haematological disorders. However, transplant technology and access are not uniformly distributed worldwide. Most transplants are done predominately in Europe, North America and some Asian countries. We review transplant activity in Latin America, a geographic region with a population of >600 million persons living in countries with diverse economic and social development levels. These data indicate a 20-40-fold lower frequency of transplants in Latin America compared with Europe and North America. We show that although economics, infrastructure and expertise are important limitations, other variables also operate. Changes in several of these variables may substantially increase transplant activity in Latin America.

  19. Cyclophosphamide-based hematopoietic stem cell mobilization before autologous stem cell transplantation in newly diagnosed multiple myeloma.

    PubMed

    Tuchman, Sascha A; Bacon, Wendi A; Huang, Li-Wen; Long, Gwynn; Rizzieri, David; Horwitz, Mitchell; Chute, John P; Sullivan, Keith; Morris Engemann, Ashley; Yopp, Amanda; Li, Zhiguo; Corbet, Kelly; Chao, Nelson; Gasparetto, Cristina

    2015-06-01

    High-dose cyclophosphamide (Cy) is frequently employed for peripheral blood mobilization of hematopoietic stem cells before high-dose chemotherapy with autologous stem cell transplantation (ASCT) in multiple myeloma (MM). The benefit of mobilization with Cy over filgrastim (granulocyte colony-stimulating factor; G-CSF) alone is unclear. Between 2000 and 2008, 167 patients with newly diagnosed MM underwent single ASCT after melphalan conditioning at our institution. Seventy-three patients were mobilized with G-CSF alone, and 94 patients with Cy plus G-CSF (Cy+G-CSF). We retrospectively analyzed Cy's impact on both toxicity and efficacy. Mobilization efficiency was augmented by Cy; a mean total of 12 versus 5.8 × 10(6) CD34+ cells/kg were collected from patients mobilized with Cy+G-CSF versus G-CSF, respectively, (P < 0.01), over a mean of 1.6 versus 2.2 days of peripheral blood apheresis (p = 0.001). Mobilization-related toxicity was also, however, augmented by Cy; 14% of Cy+G-CSF patients were hospitalized because of complications versus none receiving G-CSF (P < 0.0001). Toxicity, including death, related to ASCT was similar between cohorts. Regarding long-term outcomes, multivariate analysis revealed no difference for Cy+G-CSF versus G-CSF (hazard ratio 0.8 for event-free survival [95% confidence interval {CI} 0.57-1.25] and 0.96 for overall survival [95% CI 0.61-1.54]). In summary, we show that mobilization with Cy increases toxicity without positively impacting long-term outcomes in MM. Our findings place into question Cy's benefit as a routine component of stem cell mobilization regimens in MM. Randomized trials are needed to elucidate the risks and benefits of Cy more definitively.

  20. Stem Cell Transplants in Cancer Treatment

    Cancer.gov

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

  1. Cerebral toxoplasmosis after haematopoietic stem cell transplantation.

    PubMed

    Zaucha-Prażmo, Agnieszka; Samardakiewicz, Marzena; Dubelt, Joanna; Kowalczyk, Jerzy R

    2017-05-11

    Toxoplasmosis is an opportunistic infection caused by the parasite Toxoplasma gondii. The infection is severe and difficult to diagnose in patients receiving allogeneic haematopoietic stem cell transplantation (HSCT). It frequently involves the central nervous system. The case is presented of cerebral toxoplasmosis in a 17-year-old youth with Fanconi anaemia treated with haematopoietic stem cell transplantation (HSCT).

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

    PubMed

    Akan, Hamdi; Atilla, Erden

    2016-03-05

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

  3. Alemtuzumab in allogeneic hematopoetic stem cell transplantation

    PubMed Central

    Poiré, Xavier; van Besien, Koen

    2011-01-01

    Introduction With the use of reduced-intensity conditioning (RIC), early toxicity of allogeneic stem cell transplantation (SCT) has been much reduced. Graft-versus-host disease (GvHD) causes morbidities and mortality. Alemtuzumab is a mAb directed against CD52. When administered prior to transplant it leads to T-cell depletion. Incorporation of alemtuzumab in RIC results in low rates of GvHD and treatment-related mortality (TRM) in haematological diseases, even in the setting of mismatched-donor transplantation. Areas covered The use of alemtuzumab for GvHD in SCT. The benefit of alemtuzumab-based conditioning is partially offset by increased disease relapse due to impaired graft-versus-tumor effect (GvT) and by slower immune reconstitution, necessitating special precautions. While GvHD is prevented with alemtuzumab, post-SCT interventions are often required. Most studies find that alemtuzumab-based conditioning results in decreased chronic GvHD and TRM, but also in decreased progression-free survival. Overall survival after 3 – 5 years is usually equivalent and quality of life may be improved because of a lower incidence of sequelae of chronic GvHD. Many aspects of alemtuzumab treatment are under investigation. Expert opinion Alemtuzumab reduces GvHD and TRM after SCT. Use of alemtuzumab requires awareness and strict management of the risk of opportunistic infections and of an increased risk of disease recurrence. PMID:21702703

  4. Alemtuzumab in allogeneic hematopoetic stem cell transplantation.

    PubMed

    Poiré, Xavier; van Besien, Koen

    2011-08-01

    With the use of reduced-intensity conditioning (RIC), early toxicity of allogeneic stem cell transplantation (SCT) has been much reduced. Graft-versus-host disease (GvHD) causes morbidities and mortality. Alemtuzumab is a mAb directed against CD52. When administered prior to transplant, it leads to T-cell depletion. Incorporation of alemtuzumab in RIC results in low rates of GvHD and treatment-related mortality (TRM) in haematological diseases, even in the setting of mismatched-donor transplantation. The use of alemtuzumab for GvHD prophylaxis in SCT. The benefit of alemtuzumab-based conditioning is partially offset by increased disease relapse due to impaired graft-versus-tumor effect (GvT) and by slower immune reconstitution, necessitating special precautions. While GvHD is prevented with alemtuzumab, post-SCT interventions are often required. Most studies find that alemtuzumab-based conditioning results in decreased chronic GvHD and TRM, but also in decreased progression-free survival. Overall survival after 3 - 5 years is usually equivalent and quality of life may be improved because of a lower incidence of sequelae of chronic GvHD. Many aspects of alemtuzumab treatment are under investigation. Alemtuzumab reduces GvHD and TRM after SCT. Use of alemtuzumab requires awareness and strict management of the risk of opportunistic infections and of an increased risk of disease recurrence.

  5. Parasitic Infections in Hematopoietic Stem Cell Transplantation

    PubMed Central

    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. Transplantation of three-dimensional artificial human vascular tissues fabricated using an extracellular matrix nanofilm-based cell-accumulation technique.

    PubMed

    Asano, Yoshiya; Shimoda, Hiroshi; Okano, Daisuke; Matsusaki, Michiya; Akashi, Mitsuru

    2017-04-01

    We have established a novel three-dimensional (3D) tissue-constructing technique, referred to as the 'cell-accumulation method', which is based on the self-assembly of cultured human cells. In this technique, cells are coated with fibronectin and gelatin to construct extracellular matrix (ECM) nanofilms and cultured to form multi-layers in vitro. By using this method, we have successfully fabricated artificial tissues with vascular networks constructed by co-cultivation of human umbilical vein-derived vascular endothelial cells between multi-layers of normal human dermal fibroblasts. In this study, to assess these engineered vascular tissues as therapeutic implants, we transplanted the 3D human tissues with microvascular networks, fabricated based on the cell-accumulation method, onto the back skin of nude mice. After the transplantation, we found vascular networks with perfusion of blood in the transplanted graft. At the boundary between host and implanted tissue, connectivity between murine and human vessels was found. Transmission electron microscopy of the implanted artificial vascular tubules demonstrated the ultrastructural features of blood capillaries. Moreover, maturation of the vascular tissues after transplantation was shown by the presence of pericyte-like cells and abundant collagen fibrils in the ECM surrounding the vasculature. These results demonstrated that artificial human vascular tissues constructed by our method were engrafted and matured in animal skin. In addition, the implanted artificial human vascular networks were connected with the host circulatory system by anastomosis. This method is an attractive technique for engineering prevascularized artificial tissues for transplantation. Copyright © 2015 John Wiley & Sons, Ltd.

  7. Olfactory ensheathing cell transplantation for spinal cord injury: An 18-year bibliometric analysis based on the Web of Science.

    PubMed

    Leng, Zikuan; He, Xijing; Li, Haopeng; Wang, Dong; Cao, Kai

    2013-05-15

    Olfactory ensheathing cell (OEC) transplantation is a promising new approach for the treatment of spinal cord injury (SCI), and an increasing number of scientific publications are devoted to this treatment strategy. This bibliometric analysis was conducted to assess global research trends in OEC transplantation for SCI. All of the data in this study originate from the Web of Science maintained by the Institute for Scientific Information, USA, and includes SCI-EXPANDED, SSCI, A&HCI, CPCI-S, CPCI-SSH, BKCI-S, BKCI-SSH, CCR-EXPANDED and IC. The Institute for Scientific Information's Web of Science was searched using the keywords "olfactory ensheathing cells" or "OECs" or "olfactory ensheathing glia" or "OEG" or "olfactory ensheathing glial cells" or "OEGs" and "spinal cord injury" or "SCI" or "spinal injury" or "spinal transection" for literature published from January 1898 to May 2012. Original articles, reviews, proceedings papers and meeting abstracts, book chapters and editorial materials on OEC transplantation for SCI were included. Simultaneously, unpublished literature and literature for which manual information retrieval was required were excluded. ALL SELECTED LITERATURES ADDRESSING OEC TRANSPLANTATION FOR SCI WERE EVALUATED IN THE FOLLOWING ASPECTS: publication year, document type, language, author, institution, times cited, Web of Science category, core source title, countries/territories and funding agency. In the Web of Science published by the Institute for Scientific Information, the earliest literature record was in April, 1995. Four hundred and fourteen publications addressing OEC transplantation for SCI were added to the data library in the past 18 years, with an annually increasing trend. Of 415 records, 405 publications were in English. Two hundred and fifty-nine articles ranked first in the distribution of document type, followed by 141 reviews. Thirty articles and 20 reviews, cited more than 55 times by the date the publication data were

  8. Thrombotic microangiopathy associated with sirolimus levels following allogeneic hematopoietic cell transplantation with tacrolimus/sirolimus-based GVHD prophylaxis

    PubMed Central

    Shayani, Sepideh; Palmer, Joycelynne; Stiller, Tracey; Liu, Xueli; Thomas, Sandra H.; Khuu, Tam; Parker, Pablo M.; Khaled, Samer K.; Forman, Stephen J.; Nakamura, Ryotaro

    2013-01-01

    Post-transplant thrombotic microangiopathy (TMA) is a multi-factorial complication of allogeneic hematopoietic cell transplantation (allo-HCT) whose incidence is increased when using a sirolimus plus tacrolimus regimen for acute graft-versus-host disease (aGVHD) prophylaxis. We evaluated the incidence and possible risk factors for TMA in a case series of 177 patients who received allo-HCT using SIR/TAC-based GVHD prophylaxis. Donors were either sibling (n=82) or matched unrelated (n=95). Within the first 100 days post-HCT, 30 (17%) patients were diagnosed with TMA, and an additional nine patients (5%) were classified as probable TMA cases. The median time to TMA onset was 4.6 weeks (range: 1.6-10.6). Thirty-four patients developed both TMA and aGVHD, with the majority of patients (81%) developing aGVHD first. By multivariable analysis, the following factors were found to be associated with increased risk of TMA: day 14 serum sirolimus: ≥9.9 ng/ml (HR: 2.19, 95% CI: 1.13-4.27, p=0.02), presence of prior aGVHD grades II-IV (HR: 3.04, 95% CI: 1.38-6.71, p<0.01), and fully myeloablative conditioning (HR: 3.47, 95% CI: 1.60-7.53, p<0.01). The risk factors for TMA suggest that when using sirolimus/tacrolimus for GVHD prophylaxis, careful monitoring and adjustment of sirolimus dosages is critical, particularly in patients with active aGVHD. PMID:23078784

  9. Outcomes of Haploidentical Stem Cell Transplantation for Lymphoma with Melphalan-Based Conditioning.

    PubMed

    Brammer, Jonathan E; Khouri, Issa; Gaballa, Sameh; Anderlini, Paolo; Tomuleasa, Ciprian; Ahmed, Sairah; Ledesma, Celina; Hosing, Chitra; Champlin, Richard E; Ciurea, Stefan O

    2016-03-01

    Haploidentical transplantation (Haplo-SCT) with post-transplantation cyclophosphamide (PTCy) is increasingly utilized for the treatment of lymphoma and almost exclusively with the nonmyeloablative fludarabine (Flu)/cyclophosphamide/total body irradiation (TBI) conditioning regimen. We present early results of a reduced-intensity (RIC) regimen utilizing fludarabine and melphalan (FM) for the treatment of advanced lymphoma. All patients with a diagnosis of lymphoma or chronic lymphocytic leukemia (CLL) who received Haplo-SCT at the University of Texas MD Anderson Cancer Center between 2009 and 2014 were reviewed (N = 22). Patients received Flu 160 mg/m(2) and melphalan 100 mg/m(2) to 140 mg/m(2) with thiotepa 5 mg/kg or 2 Gy TBI. Because of concerns of increased treatment-related mortality (TRM) with the melphalan 140 mg/m(2) regimen (FM140), a RIC regimen with melphalan 100 mg/m(2) (FM100) was devised. Rituximab was included for CD20(+) disease. Graft-versus-host disease prophylaxis consisted of PTCy 50 mg/kg on days +3 and + 4, tacrolimus, and mycophenolate mofetil. Sixty-eight percent of all patients were not in complete remission at the time of transplantation. The 2-year progression-free survival (PFS) and overall survival (OS) for the entire cohort were 54%, 1-year TRM was 19%, and the cumulative incidence of relapse at 2 years was 27%. Two-year PFS for Hodgkin lymphoma, non-Hodgkin lymphoma, and CLL/small lymphocytic lymphoma were 57%, 51%, and 75%. Patients treated with FM100 compared to FM140 had equivalent PFS (71% versus 37%, P = .246) and OS (71% versus 58%, P = .32). These early results establish Flu and melphalan 100 mg/m(2) with 2 Gy TBI or thiotepa 5 mg/kg as a very promising conditioning regimen for the treatment of advanced lymphoma with Haplo-SCT and PTCy. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  10. Neural stem cell transplantation in mouse brain.

    PubMed

    Lee, Jean-Pyo; McKercher, Scott; Muller, Franz-Josef; Snyder, Evan Y

    2008-01-01

    Neural stem cells (NSCs) are the most primordial, least committed cells of the nervous system, and transplantation of these multipotent cells holds the promise of regenerative therapy for many central nervous system (CNS) diseases. This unit describes methods for NSC transplantation into neonatal mouse pups, embryonic mouse brain, and adult mouse brain. A description of options for detection of labeled donor cells in engrafted mouse brain is provided along with an example protocol for detecting lacZ-expressing cells in situ. Also included is a protocol for preparing NSCs for transplantation.

  11. Organ or Stem Cell Transplant and Your Mouth

    MedlinePlus

    Organ or Stem Cell Transplant and Your Mouth KEY POINTS n Have a dental checkup before your transplant procedure. n See your ... problems . SEE YOUR DENTIST Before an organ or stem cell transplant, have a dental checkup. Your mouth BEFORE ...

  12. Fibrin patch-based insulin-like growth factor-1 gene-modified stem cell transplantation repairs ischemic myocardium

    PubMed Central

    Li, Jun; Zhu, Kai; Yang, Shan; Wang, Yulin; Guo, Changfa; Yin, Kanhua; Wang, Chunsheng

    2015-01-01

    Bone marrow mesenchymal stem cells (BMSCs), tissue-engineered cardiac patch, and therapeutic gene have all been proposed as promising therapy strategies for cardiac repair after myocardial infarction. In our study, BMSCs were modified with insulin-like growth factor-1 (IGF-1) gene, loaded into a fibrin patch, and then transplanted into a porcine model of ischemia/reperfusion (I/R) myocardium injury. The results demonstrated that IGF-1 gene overexpression could promote proliferation of endothelial cells and cardiomyocyte-like differentiation of BMSCs in vitro. Four weeks after transplantation of fibrin patch loaded with gene-modified BMSCs, IGF-1 overexpression could successfully promote angiogenesis, inhibit remodeling, increase grafted cell survival and reduce apoptosis. In conclusion, the integrated strategy, which combined fibrin patch with IGF-1 gene modified BMSCs, could promote the histological cardiac repair for a clinically relevant porcine model of I/R myocardium injury. PMID:25767192

  13. [Allogeneic hematopoietic stem cell transplantation in Hungary].

    PubMed

    Bátai, Árpád; Reményi, Péter; Réti, Marienn; Barta, Anikó; Gopcsa, László; Lengyel, Lilla; Torbágyi, Éva; Csukly, Zoltán; Karászi, Éva; Tordai, Attila; Andrikovics, Hajnalka; Balassa, Katalin; Tasnády, Szabolcs; Masszi, Tamás

    2017-02-01

    The publication summarizes the 2548 stem cell transplantations performed in the period of 1993-2015 in Szent Laszló Hospital, Budapest and provides a detailed discussion of the 425 allogeneic transplantations during 2007-2013. The analysis explains the major steps of the evolution of allogeneic stem cell transplantation and compares the results of the unique Hungarian allogeneic center. The significant shift in the transplantation indications from chronic myeloid leukemia to myelodysplastic syndromes and the rising age of the recipients are in line with world wide tendencies. The latter one is the consequence of the introduction and improvement of the concept of reduced intensity conditioning regimens, originally arising from the idea of Endre Kelemen. The most limiting factor, the donor availability seems to be resolved with the use of a new immunomodulating regimen, the application of posttransplantation cyclophosphamide, which allows the transplantation through HLA barriers with haploidentical family donors with comparable results to the HLA matched volunteer unrelated donors. The above mentioned tendencies result the wider use of allogeneic stem cell transplantation less dependent from recipient age, comorbidities and even donor availability. The publication highlights the need of expanding the stem cell transplantation budget and the involvement of new centers in Hungary in allogeneic of stem cell transplantation. Orv. Hetil., 2017, 158(8), 291-297.

  14. Hospital infection control in hematopoietic stem cell transplant recipients.

    PubMed Central

    Dykewicz, C. A.

    2001-01-01

    Guidelines for Preventing Opportunistic Infections Among Hematopoietic Stem Cell Transplant Recipients contains a section on hospital infection control including evidence-based recommendations regarding ventilation, construction, equipment, plants, play areas and toys, health-care workers, visitors, patient skin and oral care, catheter-related infections, drug-resistant organisms, and specific nosocomial infections. These guidelines are intended to reduce the number and severity of hospital infections in hematopoietic stem cell transplant recipients. PMID:11294720

  15. Pharmacogenetic aspects of drug metabolizing enzymes in busulfan based conditioning prior to allogenic hematopoietic stem cell transplantation in children.

    PubMed

    Huezo-Diaz, Patricia; Uppugunduri, Chakradhara Rao S; Tyagi, Anuj Kumar; Krajinovic, Maja; Ansari, Marc

    2014-03-01

    Allogenic hematopoietic stem cell transplantation (HSCT) is a well established but complex treatment option for malignant and non-malignant disorders in pediatric patients. Most commonly used myeloablative and non-myeloablative conditioning regimens in children comprise alkylating agents, such as busulfan (BU) and cyclophosphamide. Inter-individual variability in the pharmacokinetics of BU can result in altered conditioning of the patient and therefore lead to relapse or rejection due to under exposures, or occurrence of toxicities due to over exposures. With the introduction of the intravenous formulation of BU, this variability has been reduced but still cannot be fully predicted. Inter and intra-individual variability of BU kinetics is more common in children compared to adults and toxicity of BU based regimens is still a concern. It has been hypothesized that some of this variability in BU pharmacokinetics and treatment outcomes, especially the toxicity, might be predicted by genetic variants of enzymes involved in the metabolism of BU. This review intends to summarize the studies performed to date on the pharmacokinetics and pharmacogenetics of BU based conditioning, specifically in relation to children.

  16. Hematopoietic Stem cell transplantation and lentiviral vector‐based gene therapy for Krabbe's disease: Present convictions and future prospects

    PubMed Central

    Hu, Peirong; Li, Yedda; Nikolaishvili‐Feinberg, Nana; Scesa, Giuseppe; Bi, Yanmin; Pan, Dao; Moore, Dominic; Bongarzone, Ernesto R.; Sands, Mark S.; Miller, Ryan

    2016-01-01

    Currently, presymtomatic hematopoietic stem and progenitor cell transplantation (HSPCT) is the only therapeutic modality that alleviates Krabbe's disease (KD)‐induced central nervous system damage. However, all HSPCT‐treated patients exhibit severe deterioration in peripheral nervous system function characterized by major motor and expressive language pathologies. We hypothesize that a combination of several mechanisms contribute to this phenomenon, including 1) nonoptimal conditioning protocols with consequent inefficient engraftment and biodistribution of donor‐derived cells and 2) insufficient uptake of donor cell‐secreted galactocerebrosidease (GALC) secondary to a naturally low expression level of the cation‐independent mannose 6‐phosphate‐receptor (CI‐MPR). We have characterized the effects of a busulfan (Bu) based conditioning regimen on the efficacy of HSPCT in prolonging twi mouse average life span. There was no correlation between the efficiency of bone marrow engraftment of donor cells and twi mouse average life span. HSPCT prolonged the average life span of twi mice, which directly correlated with the aggressiveness of the Bu‐mediated conditioning protocols. HSPC transduced with lentiviral vectors carrying the GALC cDNA under control of cell‐specific promoters were efficiently engrafted in twi mouse bone marrow. To facilitate HSPCT‐mediated correction of GALC deficiency in target cells expressing low levels of CI‐MPR, a novel GALC fusion protein including the ApoE1 receptor was developed. Efficient cellular uptake of the novel fusion protein was mediated by a mannose‐6‐phosphate‐independent mechanism. The novel findings described here elucidate some of the cellular mechanisms that impede the cure of KD patients by HSPCT and concomitantly open new directions to enhance the therapeutic efficacy of HSPCT protocols for KD. © 2016 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc. PMID:27638600

  17. Transplantation Tolerance Induction: Cell Therapies and Their Mechanisms.

    PubMed

    Scalea, Joseph R; Tomita, Yusuke; Lindholm, Christopher R; Burlingham, William

    2016-01-01

    Cell-based therapies have been studied extensively in the context of transplantation tolerance induction. The most successful protocols have relied on transfusion of bone marrow prior to the transplantation of a renal allograft. However, it is not clear that stem cells found in bone marrow are required in order to render a transplant candidate immunologically tolerant. Accordingly, mesenchymal stem cells, regulatory myeloid cells, T regulatory cells, and other cell types are being tested as possible routes to tolerance induction, in the absence of donor-derived stem cells. Early data with each of these cell types have been encouraging. However, the induction regimen capable of achieving consistent tolerance, while avoiding unwanted sided effects, and which is scalable to the human patient, has yet to be identified. Here, we present the status of investigations of various tolerogenic cell types and the mechanistic rationale for their use in tolerance induction protocols.

  18. Transplantation Tolerance Induction: Cell Therapies and Their Mechanisms

    PubMed Central

    Scalea, Joseph R.; Tomita, Yusuke; Lindholm, Christopher R.; Burlingham, William

    2016-01-01

    Cell-based therapies have been studied extensively in the context of transplantation tolerance induction. The most successful protocols have relied on transfusion of bone marrow prior to the transplantation of a renal allograft. However, it is not clear that stem cells found in bone marrow are required in order to render a transplant candidate immunologically tolerant. Accordingly, mesenchymal stem cells, regulatory myeloid cells, T regulatory cells, and other cell types are being tested as possible routes to tolerance induction, in the absence of donor-derived stem cells. Early data with each of these cell types have been encouraging. However, the induction regimen capable of achieving consistent tolerance, while avoiding unwanted sided effects, and which is scalable to the human patient, has yet to be identified. Here, we present the status of investigations of various tolerogenic cell types and the mechanistic rationale for their use in tolerance induction protocols. PMID:27014267

  19. The effect of dendritic cells on the retinal cell transplantation

    SciTech Connect

    Oishi, Akio; Nagai, Takayuki; Mandai, Michiko Takahashi, Masayo; Yoshimura, Nagahisa

    2007-11-16

    The potential of bone marrow cell-derived immature dendritic cells (myeloid iDCs) in modulating the efficacy of retinal cell transplantation therapy was investigated. (1) In vitro, myeloid iDCs but not BMCs enhanced the survival and proliferation of embryonic retinal cells, and the expression of various neurotrophic factors by myeloid iDCs was confirmed with RT-PCR. (2) In subretinal transplantation, neonatal retinal cells co-transplanted with myeloid iDCs showed higher survival rate compared to those transplanted without myeloid iDCs. (3) CD8 T-cells reactive against donor retinal cells were significantly increased in the mice with transplantation of retinal cells alone. These results suggested the beneficial effects of the use of myeloid iDCs in retinal cell transplantation therapy.

  20. Hematopoetic stem cell transplantation in children

    PubMed Central

    Yeşilipek, Mehmet Akif

    2014-01-01

    Bone marrow transplantation is called hematopoetic stem cell transplantation (HSCT), since peripheral blood and umbilical cord blood can also be used as sources of stem cell currently. In children, bone marrow transplantation is used as a definite treatment method in many diseases including hemoglobinopaties, immune deficiencies, bone marrow failure and congenital metabolic diseases in addition to hematological malignancies. In addition to the underlying disease, the most important factors which have an impact on prognosis include infections which develop during the process of transplantation and graft-versus-host disease. In this article, it was aimed to give brief information on stem cell sources, preparation therapies, HSCT indications and post-transplantation complications in children. PMID:26078642

  1. Insights in Behavior of Variably Formulated Alginate-Based Microcapsules for Cell Transplantation

    PubMed Central

    Montanucci, Pia; Terenzi, Silvia; Pennoni, Ilaria; Basta, Giuseppe; Calafiore, Riccardo

    2015-01-01

    Alginate-based microencapsulation of live cells may offer the opportunity to treat chronic and degenerative disorders. So far, a thorough assessment of physical-chemical behavior of alginate-based microbeads remains cloudy. A disputed issue is which divalent cation to choose for a high performing alginate gelling process. Having selected, in our system, high mannuronic (M) enriched alginates, we studied different gelling cations and their combinations to determine their eventual influence on physical-chemical properties of the final microcapsules preparation, in vitro and in vivo. We have shown that used of ultrapure alginate allows for high biocompatibility of the formed microcapsules, regardless of gelation agents, while use of different gelling cations is associated with corresponding variable effects on the capsules' basic architecture, as originally reported in this work. However, only the final application which the capsules are destined to will ultimately guide the selection of the ideal, specific gelling divalent cations, since in principle there are no capsules that are better than others. PMID:26078974

  2. Daylight vision repair by cell transplantation.

    PubMed

    Santos-Ferreira, Tiago; Postel, Kai; Stutzki, Henrike; Kurth, Thomas; Zeck, Günther; Ader, Marius

    2015-01-01

    Human daylight vision depends on cone photoreceptors and their degeneration results in visual impairment and blindness as observed in several eye diseases including age-related macular degeneration, cone-rod dystrophies, or late stage retinitis pigmentosa, with no cure available. Preclinical cell replacement approaches in mouse retina have been focusing on rod dystrophies, due to the availability of sufficient donor material from the rod-dominated mouse retina, leaving the development of treatment options for cone degenerations not well studied. Thus, an abundant and traceable source for donor cone-like photoreceptors was generated by crossing neural retina leucine zipper-deficient (Nrl(-/-) ) mice with an ubiquitous green fluorescent protein (GFP) reporter line resulting in double transgenic tg(Nrl(-/-); aGFP) mice. In Nrl(-/-) retinas, all rods are converted into cone-like photoreceptors that express CD73 allowing their enrichment by CD73-based magnetic activated cell sorting prior transplantation into the subretinal space of adult wild-type, cone-only (Nrl(-/-)), or cone photoreceptor function loss 1 (Cpfl1) mice. Donor cells correctly integrated into host retinas, acquired mature photoreceptor morphology, expressed cone-specific markers, and survived for up to 6 months, with significantly increased integration rates in the cone-only Nrl(-/-) retina. Individual retinal ganglion cell recordings demonstrated the restoration of photopic responses in cone degeneration mice following transplantation suggesting, for the first time, the feasibility of daylight vision repair by cell replacement in the adult mammalian retina. © 2014 AlphaMed Press.

  3. Micron-sized iron oxide-containing particles for microRNA-targeted manipulation and MRI-based tracking of transplanted cells.

    PubMed

    Leder, Annekatrin; Raschzok, Nathanael; Schmidt, Christian; Arabacioglu, Duygu; Butter, Antje; Kolano, Susanne; de Sousa Lisboa, Luisa S; Werner, Wiebke; Polenz, Dietrich; Reutzel-Selke, Anja; Pratschke, Johann; Sauer, Igor M

    2015-05-01

    Particle-based delivery systems for therapeutic manipulation and tracking of transplanted cells by magnetic resonance imaging (MRI) are commonly based on nanometer-sized superparamagnetic iron oxide particles (SPIOs). Here, we present a proof of concept for multifunctional, silica based micron-sized iron oxide-containing particles (sMPIO) that combine fluorescence imaging, MRI tracking, and on-the-spot targeting of specific microRNAs on a particle surface for therapeutic manipulation by RNA interference. Antisense locked nucleic acids (α-LNA) were covalently bound to the surface of silica-based, DAPI-integrated, micron-sized iron oxide particles (sMPIO-α-LNA). In vitro studies using primary human hepatocytes showed rapid particle uptake (4 h) that was accompanied by significant depletion of the targeted microRNA Let7g (80%), up-regulation of the target proteins Cyclin D1 and c-Myc, and specific proteome changes. sMPIO-α-LNA-labeled cells were successfully detected by fluorescence imaging and could be visualized by MRI after intrasplenic transplantation in rats. This new theranostic particle provides a promising tool for cell transplantation where cellular imaging and microRNA-based manipulation is needed. [165]. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Bone marrow transplant

    MedlinePlus

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

  5. A Hyaluronan-Based Injectable Hydrogel Improves the Survival and Integration of Stem Cell Progeny following Transplantation.

    PubMed

    Ballios, Brian G; Cooke, Michael J; Donaldson, Laura; Coles, Brenda L K; Morshead, Cindi M; van der Kooy, Derek; Shoichet, Molly S

    2015-06-09

    The utility of stem cells and their progeny in adult transplantation models has been limited by poor survival and integration. We designed an injectable and bioresorbable hydrogel blend of hyaluronan and methylcellulose (HAMC) and tested it with two cell types in two animal models, thereby gaining an understanding of its general applicability for enhanced cell distribution, survival, integration, and functional repair relative to conventional cell delivery in saline. HAMC improves cell survival and integration of retinal stem cell (RSC)-derived rods in the retina. The pro-survival mechanism of HAMC is ascribed to the interaction of the CD44 receptor with HA. Transient disruption of the retinal outer limiting membrane, combined with HAMC delivery, results in significantly improved rod survival and visual function. HAMC also improves the distribution, viability, and functional repair of neural stem and progenitor cells (NSCs). The HAMC delivery system improves cell transplantation efficacy in two CNS models, suggesting broad applicability. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Evolving approaches of hematopoietic stem cell-based therapies to induce tolerance to organ transplants: the long road to tolerance.

    PubMed

    Leventhal, J; Miller, J; Abecassis, M; Tollerud, D J; Ildstad, S T

    2013-01-01

    The immunoregulatory properties of hematopoietic stem cells (HSCs) have been recognized for more than 60 years, beginning in 1945, when Owen reported that genetically disparate freemartin cattle sharing a common placenta were red blood cell chimeras. In 1953, Billingham, Brent, and Medawar demonstrated that murine neonatal chimeras prepared by infusion of donor-derived hematopoietic cells exhibited donor-specific tolerance to skin allografts. Various approaches using HSCs in organ transplantation have gradually brought closer to reality the dream of inducing donor-specific tolerance in organ transplant recipients. Several hurdles needed to be overcome, especially the risk of graft-versus-host disease (GVHD), the toxicity of ablative conditioning, and the need for close donor-recipient matching. For wide acceptance, HSC therapy must be safe and reproducible in mismatched donor-recipient combinations. Discoveries in other disciplines have often unexpectedly and synergistically contributed to progress in this area. This review presents a historic perspective of the quest for tolerance in organ transplantation, highlighting current clinical approaches.

  7. Cell replacement and visual restoration by retinal sheet transplants

    PubMed Central

    Seiler, Magdalene J.; Aramant, Robert B.

    2012-01-01

    Retinal diseases such as age-related macular degeneration (ARMD) and retinitis pigmentosa (RP) affect millions of people. Replacing lost cells with new cells that connect with the still functional part of the host retina might repair a degenerating retina and restore eyesight to an unknown extent. A unique model, subretinal transplantation of freshly dissected sheets of fetal-derived retinal progenitor cells, combined with its retinal pigment epithelium (RPE), has demonstrated successful results in both animals and humans. Most other approaches are restricted to rescue endogenous retinal cells of the recipient in earlier disease stages by a ‘nursing’ role of the implanted cells and are not aimed at neural retinal cell replacement. Sheet transplants restore lost visual responses in several retinal degeneration models in the superior colliculus (SC) corresponding to the location of the transplant in the retina. They do not simply preserve visual performance – they increase visual responsiveness to light. Restoration of visual responses in the SC can be directly traced to neural cells in the transplant, demonstrating that synaptic connections between transplant and host contribute to the visual improvement. Transplant processes invade the inner plexiform layer of the host retina and form synapses with presumable host cells. In a Phase II trial of RP and ARMD patients, transplants of retina together with its RPE improved visual acuity. In summary, retinal progenitor sheet transplantation provides an excellent model to answer questions about how to repair and restore function of a degenerating retina. Supply of fetal donor tissue will always be limited but the model can set a standard and provide an informative base for optimal cell replacement therapies such as embryonic stem cell (ESC)-derived therapy. PMID:22771454

  8. Results of a phase I/II British Society of Bone Marrow Transplantation study on PCR-based pre-emptive therapy with valganciclovir or ganciclovir for active CMV infection following alemtuzumab-based reduced intensity allogeneic stem cell transplantation.

    PubMed

    Lim, Z Y; Cook, G; Johnson, P R; Parker, Anne; Zuckerman, M; Marks, D; Wiltshire, H; Mufti, G J; Pagliuca, A

    2009-02-01

    This multi-centre randomized study assessed the bioavailability of ganciclovir in patients undergoing alemtuzumab-based reduced intensity conditioning (RIC) haematopoietic stem cell transplantation (HSCT) after oral administration of valganciclovir. Patients were randomized to 2 groups receiving either oral valganciclovir (900 mg twice daily) or intravenous ganciclovir (5mg/kg twice daily) for 14 days. Twenty-seven patients were recruited and 18 patients (67%) completed allocated treatment resulting in clearance of cytomegolovirus (CMV) DNA load at a median of 14 days. The bioavailability of ganciclovir from valganciclovir was 73% (95% CI: 34-112%). The average exposure in the valganciclovir group (36.9+/-14.9 microg h/ml) was higher than the ganciclovir cohort (27.9+/-7.5 microg h/ml). When compared with intravenous ganciclovir, oral valganciclovir had high bioavailability in patients undergoing alemtuzumab-based RIC HSCT.

  9. A mindfulness-based program for improving quality of life among hematopoietic stem cell transplantation survivors: feasibility and preliminary findings.

    PubMed

    Grossman, Paul; Zwahlen, Diana; Halter, Jorg P; Passweg, Jakob R; Steiner, Claudia; Kiss, Alexander

    2015-04-01

    Health-related quality of life (HRQoL) is often substantially reduced among individuals who have undergone hematopoietic stem cell transplantation (HSCT), and incidences of depression, fatigue, and anxiety are elevated. We examined effects of a mindfulness-based intervention (MBI) compared to psycho-oncological telephone consultation upon HRQoL, depression, anxiety, and fatigue among HSCT survivors. Sixty-two medically stable patients participated in the study; they had completed HSCT ≥6 months previously. Thirty-two were randomly assigned to intervention arms, and 30 were offered their treatment preference. MBI consisted of a structured 8-week program of mindfulness training. Assessments were made at baseline, post-intervention and 3 months follow-up. Primary outcome was HRQoL. Depression, fatigue, anxiety, and personal goal attainment were secondary measures. Non-completion of interventions was low in both groups (9 %, MBI; 7 % control). Employing intention-to-treat analysis, MBI, compared with comparison procedure, improved HRQoL and reduced depression and anxiety at post-intervention (p's < 0.05); Cohen's d effect sizes, 0.6-0.7; 3-month follow-up benefits were modest. These findings demonstrate broad feasibility and acceptance of, as well as satisfaction and adherence with, a program of mindfulness training for HSCT survivors; findings also suggest improved HRQoL and well-being as a consequence of MBI. Nevertheless, this is a preliminary study; a larger trial with more prolonged intervention phase is warranted.

  10. A Novel Suture-Based Method for Efficient Transplantation of Stem Cells

    PubMed Central

    Guyette, Jacques P.; Fakharzadeh, Michael; Burford, Evans J.; Tao, Ze-wei; Pins, George D.; Rolle, Marsha W.; Gaudette, Glenn R.

    2012-01-01

    Advances in regenerative medicine have improved the potential of using cellular therapy for treating several diseases. However, the effectiveness of new cellular therapies is largely limited by low cell engraftment and inadequate localization. To improve upon these limitations, we developed a novel delivery mechanism using cell-seeded biological sutures. Herein, we demonstrate the ability of cell-seeded biological sutures to efficiently implant human mesenchymal stem cells (hMSCs) to specific regions within the beating heart; a tissue known to have low cell retention and engraftment shortly after delivery. Cell-seeded biological sutures were developed by bundling discrete microthreads extruded from extracellular matrix proteins, attaching a surgical needle to the bundle, and seeding the bundle with hMSCs. Prior to cell preparation, hMSCs were loaded with quantum dot (QD) nanoparticles for cell tracking within the myocardium. Each biological suture contained an average of 5,903 ± 1,966 hMSCs/cm suture length. Delivery efficiency was evaluated by comparing cell-seeded biological suture implantation with intramyocardial cell injections (10,000 hMSCs in 35 µL) into the left ventricle of normal, non-infarcted rat hearts after one hour. Delivery efficiency of hMSCs by biological sutures (63.6 ± 10.6%) was significantly higher than intramyocardial injection (11.8 ± 6.2%; p < 0.05). Cell-tracking analysis indicated suture-delivered hMSCs were found throughout the thickness of the ventricular myocardium; along the entire length of the biological suture track, localizing closely with native myocardium. These results suggest cell-seeded biological sutures can deliver cells to the heart more efficiently than conventional methods, demonstrating an effective delivery method for implanting cells in soft tissue. PMID:22961975

  11. Next-generation sequencing-based detection of circulating tumour DNA After allogeneic stem cell transplantation for lymphoma.

    PubMed

    Herrera, Alex F; Kim, Haesook T; Kong, Katherine A; Faham, Malek; Sun, Heather; Sohani, Aliyah R; Alyea, Edwin P; Carlton, Victoria E; Chen, Yi-Bin; Cutler, Corey S; Ho, Vincent T; Koreth, John; Kotwaliwale, Chitra; Nikiforow, Sarah; Ritz, Jerome; Rodig, Scott J; Soiffer, Robert J; Antin, Joseph H; Armand, Philippe

    2016-12-01

    Next-generation sequencing (NGS)-based circulating tumour DNA (ctDNA) detection is a promising monitoring tool for lymphoid malignancies. We evaluated whether the presence of ctDNA was associated with outcome after allogeneic haematopoietic stem cell transplantation (HSCT) in lymphoma patients. We studied 88 patients drawn from a phase 3 clinical trial of reduced-intensity conditioning HSCT in lymphoma. Conventional restaging and collection of peripheral blood samples occurred at pre-specified time points before and after HSCT and were assayed for ctDNA by sequencing of the immunoglobulin or T-cell receptor genes. Tumour clonotypes were identified in 87% of patients with adequate tumour samples. Sixteen of 19 (84%) patients with disease progression after HSCT had detectable ctDNA prior to progression at a median of 3·7 months prior to relapse/progression. Patients with detectable ctDNA 3 months after HSCT had inferior progression-free survival (PFS) (2-year PFS 58% vs. 84% in ctDNA-negative patients, P = 0·033). In multivariate models, detectable ctDNA was associated with increased risk of progression/death (Hazard ratio 3·9, P = 0·003) and increased risk of relapse/progression (Hazard ratio 10·8, P = 0·0006). Detectable ctDNA is associated with an increased risk of relapse/progression, but further validation studies are necessary to confirm these findings and determine the clinical utility of NGS-based minimal residual disease monitoring in lymphoma patients after HSCT.

  12. Hematopoietic stem cell transplantation in Algeria.

    PubMed

    Bekadja, Mohamed Amine; Brahimi, Mohamed; Osmani, Soufi; Yafour, Nabil; Krim, Amina; Serradj, Faiza; Talhi, Souad; Amani, Kamila; Bouhass, Rachid Amar

    2017-07-11

    Algeria is a country of 40,.4 million inhabitants and half of which is under 30years. In Algeria, Health-care insurance covered, 90% of the population. Health care is free and it is supported by the Ministry of Health. 16 university hospitals exist in Algeria and only two (Algiers and Oran) practicing bone marrow transplant. Adult hematologic malignancies account for 10% (about 4000 new cases/year) of the malignancy affecting in most cases young patients under 65years of age. In 2016, 270 transplants were performed in total (Algiers+Oran), including 149 allografts (related donor transplants: 99%) and 121 autografts. 98% of transplants are done in adults and only 2% in children with cord blood transplants. In summary for the two transplant centers, the predominant types of transplantation performed are allogeneic transplant in 55% and autologous transplant in 45%. The particularity of EHU1st November in Oran, is the use of non-cryopreserved stem cells. Stem cell was mobilized using G-CSF alone and the grafts were kept in a conventional blood bank refrigerator at +4°C until reinfusion on day 0. The outcome with non-cryopreserved stem cells are the same as those with cryopreserved stem cells and we conclude that autologous transplant with non cryopreserved hematopoietic stem cells (HSC) is a simple, effective and safe method and the cryopreservation is not necessary in our work conditions in developing countries. The projects are achieving the autograft in all University Hospitals with non cryopreserved HSC, achieving a center allograft in the east of the country and the development of bone marrow transplantation in children. Currently in Algeria, the number of transplantation is insufficient and the development of new transplant centers is essential. In the future, we hope to implement the National Society of Bone Marrow transplant and also the National recipient registry and Donor registry in Algeria. Copyright © 2017 King Faisal Specialist Hospital & Research

  13. [Altered gut bacterial flora and organic acids in feces of patients undergoing autologous stem cell transplantation with quinolone-based antibacterial prophylaxis].

    PubMed

    Hagiwara, Shotaro; Hagiwara, Shotaro; Asahara, Takashi; Nomoto, Koji; Morotomi, Masami; Ishizuka, Naoki; Miwa, Akiyoshi; O Yoshida, Takato

    2010-06-01

    Gastrointestinal toxicity and various infections are serious problems associated with high-dose chemotherapy. Antibacterial chemoprophylaxis reduces the incidence of gram-negative bacterial infection; however, it may affect the normal intestinal flora and induce drug resistance in organisms. We evaluated the chronological changes in fecal bacteria and organic acids in 6 patients undergoing autologous stem cell transplantation with quinolone-based chemoprophylaxis. All patients developed grade 2-3 diarrhea. Four patients developed grade 3 febrile neutropenia. The total count of obligatory anaerobic bacteria was significantly decreased on Day 7, but total facultative anaerobic bacterial count did not change throughout transplantation. However, Enterobacteriaceae and Lactobacillus were decreased on Day 7 and Staphylococcus was increased after transplantation. Total organic acid concentration and short-chain fatty acids were decreased on Day 7. The bacterial flora and organic acids in the gut were significantly altered in patients who underwent autologous stem cell transplantation with quinolonebased chemoprophylaxis. These changes may contribute to gastrointestinal toxicity and infections.

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

    NASA Astrophysics Data System (ADS)

    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.

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

    ClinicalTrials.gov

    2017-01-12

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

  16. Transfusion Support for ABO-Incompatible Progenitor Cell Transplantation

    PubMed Central

    Kopko, Patricia M.

    2016-01-01

    Summary ABO-incompatible transplants comprise up to 50% of allogeneic progenitor cell transplants. Major, minor and bidirectional ABO-incompatible transplants each have unique complications that can occur, including hemolysis at the time of progenitor cell infusion, hemolysis during donor engraftment, passenger lymphocyte syndrome, delayed red blood cell engraftment, and pure red cell aplasia. Appropriate transfusion support during the different phases of the allogeneic progenitor cell transplant process is an important part of ABO-incompatible transplantation. PMID:27022318

  17. Islet transplantation in type 1 diabetic patients using calcineurin inhibitor-free immunosuppressive protocols based on T-cell adhesion or costimulation blockade.

    PubMed

    Posselt, Andrew M; Szot, Gregory L; Frassetto, Lynda A; Masharani, Umesh; Tavakol, Mehdi; Amin, Raj; McElroy, Joan; Ramos, Marissa D; Kerlan, Robert K; Fong, Lawrence; Vincenti, Flavio; Bluestone, Jeffrey A; Stock, Peter G

    2010-12-27

    The applicability of islet transplantation as treatment for type 1 diabetes is limited by long-term graft dysfunction, immunosuppressive drug toxicity, need for multiple donors, and increased risk of allosensitization. We describe two immunosuppressive regimens based on the costimulation blocker belatacept (BELA) or the antileukocyte functional antigen-1 antibody efalizumab (EFA), which permit long-term islet allograft survival and address some of these concerns. Ten patients with type 1 diabetes with hypoglycemic unawareness received intraportal allogeneic islet transplants. Immunosuppression consisted of antithymocyte globulin induction and maintenance with sirolimus or mycophenolate and BELA (n=5) or EFA (n=5). All five BELA-treated patients achieved independence after single transplants; one resumed partial insulin use 305 days after transplant but is now independent after a second transplant. All five patients treated with EFA achieved independence after one (3/5) or two (2/5) islet transplants and remained independent while on EFA (392-804 days). After EFA was discontinued because of withdrawal of the drug from the market, two patients resumed intermittent insulin use; the others remain independent. No patient in either group developed significant side effects related to the study drugs, and none have been sensitized to alloantigens. All have stable renal function. These two novel immunosuppressive regimens are effective, well tolerated, and the first calcineurin inhibitor/steroid-sparing islet protocols resulting in long-term insulin independence. Although EFA is no longer available for clinical use, these early results demonstrate that a regimen using BELA may be an effective alternative to improve graft function and longevity while minimizing renal and β-cell toxicity.

  18. [Recent progress in hematopoietic stem cell transplantation].

    PubMed

    Shinagawa, Katsuji

    2006-06-01

    The indication for allogeneic stem cell transplantation (allo-SCT) have been expanded nowadays because many stem cell sources became available and new conditioning procedures such as reduced intensity stem cell transplantation (RIST) have been developed. Stem cell sources can be classified into bone marrow cells, peripheral blood stem cells, cord blood cells and every source derived from related or unrelated donors. Also, HLA mismatched transplantation has been studied especially in haploidentical donors. Now we must select the most compatible stem cell source for the recipient condition and disease status. RIST has expanded the indication of allo-SCT because of low regimen related toxicity. However, evaluation of graft versus leukemia (GVL) effect and control of graft versus host disease (GVHD) are still unresolved problems. Further investigations of the therapy of chronic GVHD and other posttransplant problems are warranted to improve the outcome and quality of life of the patients.

  19. The Use of Intravenous Antibiotics at the Onset of Neutropenia in Patients Receiving Outpatient-Based Hematopoietic Stem Cell Transplants

    PubMed Central

    Hamadah, Aziz; Schreiber, Yoko; Toye, Baldwin; McDiarmid, Sheryl; Huebsch, Lothar; Bredeson, Christopher; Tay, Jason

    2012-01-01

    Empirical antibiotics at the onset of febrile neutropenia are one of several strategies for management of bacterial infections in patients undergoing Hematopoietic Stem Cell Transplant (HSCT) (empiric strategy). Our HSCT program aims to perform HSCT in an outpatient setting, where an empiric antibiotic strategy was employed. HSCT recipients began receiving intravenous antibiotics at the onset of neutropenia in the absence of fever as part of our institutional policy from 01 Jan 2009; intravenous Prophylactic strategy. A prospective study was conducted to compare two consecutive cohorts [Year 2008 (Empiric strategy) vs. Year 2009 (Prophylactic strategy)] of patients receiving HSCT. There were 238 HSCTs performed between 01 Jan 2008 and 31 Dec 2009 with 127 and 111 in the earlier and later cohorts respectively. Infection-related mortality pre- engraftment was similar with a prophylactic compared to an empiric strategy (3.6% vs. 7.1%; p = 0.24), but reduced among recipients of autologous HSCT (0% vs. 6.8%; p = 0.03). Microbiologically documented, blood stream infections and clinically documented infections pre-engraftment were reduced in those receiving a prophylactic compared to an empiric strategy, (11.7% vs. 28.3%; p = 0.001), (9.9% vs. 24.4%; p = 0.003) and (18.2% vs. 33.9% p = 0.007) respectively. The prophylactic use of intravenous once-daily ceftriaxone in patients receiving outpatient based HSCT is safe and may be particularly effective in patients receiving autologous HSCT. Further studies are warranted to study the impact of this Prophylactic strategy in an outpatient based HSCT program. PMID:23029441

  20. Immunological aspects of liver cell transplantation

    PubMed Central

    Oldhafer, Felix; Bock, Michael; Falk, Christine S; Vondran, Florian W R

    2016-01-01

    Within the field of regenerative medicine, the liver is of major interest for adoption of regenerative strategies due to its well-known and unique regenerative capacity. Whereas therapeutic strategies such as liver resection and orthotopic liver transplantation (OLT) can be considered standards of care for the treatment of a variety of liver diseases, the concept of liver cell transplantation (LCTx) still awaits clinical breakthrough. Success of LCTx is hampered by insufficient engraftment/long-term acceptance of cellular allografts mainly due to rejection of transplanted cells. This is in contrast to the results achieved for OLT where long-term graft survival is observed on a regular basis and, hence, the liver has been deemed an immune-privileged organ. Immune responses induced by isolated hepatocytes apparently differ considerably from those observed following transplantation of solid organs and, thus, LCTx requires refined immunological strategies to improve its clinical outcome. In addition, clinical usage of LCTx but also related basic research efforts are hindered by the limited availability of high quality liver cells, strongly emphasizing the need for alternative cell sources. This review focuses on the various immunological aspects of LCTx summarizing data available not only for hepatocyte transplantation but also for transplantation of non-parenchymal liver cells and liver stem cells. PMID:27011904

  1. Genetically modified mesenchymal stem cells for improved islet transplantation.

    PubMed

    Wu, Hao; Ye, Zhaoyang; Mahato, Ram I

    2011-10-03

    The use of adult stem cells for therapeutic purposes has met with great success in recent years. Among several types of adult stem cells, mesenchymal stem cells (MSCs) derived from bone marrow (BM) and other sources have gained popularity for basic research and clinical applications because of their therapeutic potential in treating a variety of diseases. Because of their tissue regeneration potential and immune modulation effect, MSCs were recently used as cell-based therapy to promote revascularization, increase pancreatic β-cell proliferation, and avoid allograft rejection in islet transplantation. Taking advantage of the recent progress in gene therapy, genetically modified MSCs can further enhance and expand the therapeutic benefit of primary MSCs while retaining their stem-cell-like properties. This review aims to gain a thorough understanding of the current obstacles to successful islet transplantation and discusses the potential role of primary MSCs before or after genetic modification in islet transplantation.

  2. Catheter–Based Transendocardial Delivery of Autologous Bone-Marrow-Derived Mononuclear Cells in Patients Listed for Heart Transplantation

    PubMed Central

    Silva, Guilherme V.; Perin, Emerson C.; Dohmann, Hans F.R.; Borojevic, Radovan; Silva, Suzana A.; Sousa, Andre L.S.; Assad, Joao A.R.; Vaughn, William K.; Mesquita, Claudio T.; Belém, Luciano; Carvalho, Antonio C.; Dohmann, Hans J.F.; do Amaral, Ellen Barroso; Coutinho, Joaquim; Branco, Rodrigo; Oliveira, Edie; Willerson, James T.

    2004-01-01

    Growing evidence suggests that transplantation of autologous bone-marrow mononuclear cells (ABMMNCs) can improve the perfusion and contractile function of ischemic myocardium. This procedure could potentially benefit transplant candidates awaiting a donor heart. To study the safety and feasibility of ABMMNC injection, we performed a prospective, nonrandomized, open-label study in 5 heart transplant candidates with severe ischemic heart failure. Each patient underwent baseline single-photon emission computed tomography, a ramp treadmill protocol, 2-dimensional echocardiography, 24-hour Holter monitoring, and signal-averaged electrocardiography, which were repeated at 2 and 6 months. Transendocardial delivery of ABMMNCs was done with the aid of electromechanical mapping to identify viable myocardium. Each patient received 15 ABMMNC injections of 0.2 cc each. There were no deaths, significant arrhythmias, or other major complications. The ABMMNC injection reduced the amount of ischemic myocardium (not statistically significant). More important, exercise test results improved significantly. Myocardial volume oxygen consumption increased from 10.6 ± 3 mL/kg/min (baseline) to 16.3 ± 7 mL/kg/min (2 months) and 23 ± 7 mL/kg/min (6 months) (P = 0.0091). In 4 of the 5 cases, this was such an improvement that the patients were no longer eligible for cardiac transplantation. In addition, metabolic equivalents improved from 3.03 ± 0.66 (baseline) to 4.65 ± 1.99 (2 months) and 6.5 ± 2.0 (6 months) (P = 0.0092). In conclusion, ABMMNC injections were performed safely and resulted in improved exercise capacity. This technique may hold promise as an alternative to medical management in patients with severe ischemic heart failure who are ineligible for conventional revascularization. PMID:15562839

  3. In-Hospital Mortality and Post-Transplant Complications in Elderly Multiple Myeloma Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation: a Population-Based Study.

    PubMed

    Sanchez, Larysa; Sylvester, Michael; Parrondo, Ricardo; Mariotti, Veronica; Eloy, Jean Anderson; Chang, Victor T

    2017-03-09

    Autologous hematopoietic stem cell transplantation (auto-HSCT) has improved survival in patients with multiple myeloma (MM) and is increasingly used in elderly patients. The aim of this study was to characterize and compare in-hospital complications and mortality after auto-HSCT in younger (< age 65) vs. elderly (≥ age 65) MM patients utilizing the Nationwide Inpatient Sample (NIS). Over a three-year period (2008-2010), 2209 patients with MM were admitted to U.S. Hospitals for auto-HSCT. The median age was 59 years, with 1650 patients (74.7%) younger than age 65 and 559 patients (25.3%) age 65 or older. Overall, in-hospital mortality in MM patients following auto-HSCT was rare (1.5%) and there was no significant difference in mortality between elderly and younger patients. Elderly patients did have a significantly increased mean length of stay (18.6 days + 10.8 days (standard deviation) vs. 16.8 days + 7.2 days, p<0.001) and mean total hospital charges ($161,117 + $105,008 vs. $151,192 + $78,342, p=0.018) compared to younger pts. Elderly patients were significantly more likely than younger patients to develop major in-hospital post-transplant complications such as severe sepsis (OR 2.70, 95% CI: 1.40-5.21, p=0.003), septic shock, (OR 3.10, 95% CI: 1.43-6.71, p=0.004), pneumonia (OR 1.62, 95% CI: 1.06-2.46, p=0.024), acute respiratory failure (OR 3.44, 95% CI: 1.70-6.96, p=0.001), endotracheal intubation requiring prolonged mechanical ventilation (OR 2.19, 95% CI: 1.06-4.55, p=0.035), acute renal failure (OR 2.14, 95% CI: 1.38-3.33, p=0.001), and cardiac arrhythmias (OR 2.06, 95% CI: 1.52-2.79, <0.001). This data may help guide informed consent discussions and provide a focus for future studies to reduce treatment-related morbidity in elderly MM patients undergoing auto-HSCT.

  4. Olfactory ensheathing cell transplantation for spinal cord injury: An 18-year bibliometric analysis based on the Web of Science★

    PubMed Central

    Leng, Zikuan; He, Xijing; Li, Haopeng; Wang, Dong; Cao, Kai

    2013-01-01

    OBJECTIVE: Olfactory ensheathing cell (OEC) transplantation is a promising new approach for the treatment of spinal cord injury (SCI), and an increasing number of scientific publications are devoted to this treatment strategy. This bibliometric analysis was conducted to assess global research trends in OEC transplantation for SCI. DATA SOURCE: All of the data in this study originate from the Web of Science maintained by the Institute for Scientific Information, USA, and includes SCI-EXPANDED, SSCI, A&HCI, CPCI-S, CPCI-SSH, BKCI-S, BKCI-SSH, CCR-EXPANDED and IC. The Institute for Scientific Information's Web of Science was searched using the keywords “olfactory ensheathing cells” or “OECs” or “olfactory ensheathing glia” or “OEG” or “olfactory ensheathing glial cells” or “OEGs” and “spinal cord injury” or “SCI” or “spinal injury” or “spinal transection” for literature published from January 1898 to May 2012. DATA SELECTION: Original articles, reviews, proceedings papers and meeting abstracts, book chapters and editorial materials on OEC transplantation for SCI were included. Simultaneously, unpublished literature and literature for which manual information retrieval was required were excluded. MAIN OUTCOME MEASURES: All selected literatures addressing OEC transplantation for SCI were evaluated in the following aspects: publication year, document type, language, author, institution, times cited, Web of Science category, core source title, countries/territories and funding agency. RESULTS: In the Web of Science published by the Institute for Scientific Information, the earliest literature record was in April, 1995. Four hundred and fourteen publications addressing OEC transplantation for SCI were added to the data library in the past 18 years, with an annually increasing trend. Of 415 records, 405 publications were in English. Two hundred and fifty-nine articles ranked first in the distribution of document type, followed by 141

  5. Allogeneic stem cell transplantation for thalassemia major.

    PubMed

    Mathews, Vikram; Srivastava, Alok; Chandy, Mammen

    2014-12-01

    Allogeneic stem cell transplant remains the only curative option for β-thalassemia major. In patients with good risk features it is reasonable to anticipate a greater than 90% chance of a successful transplant outcome. The conventional risk stratification system has limitations and alternative systems are being explored to better identify subsets that require innovative approaches. Several novel regimens have been evaluated to reduce treatment-related morbidity and mortality. There remain challenges in improving the clinical outcome of high-risk patients. There are limited data on the role of splenectomy before transplantation or optimal posttransplant chelation and care of these patients. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Blood-Forming Stem Cell Transplants

    MedlinePlus

    ... Health Professionals Questions to Ask about Your Treatment Research Blood-Forming Stem Cell Transplants On This Page What are bone marrow ... are evaluating BMT and PBSCT in clinical trials (research studies) for the treatment ... are the donor’s stem cells matched to the patient’s stem cells in allogeneic ...

  7. [Hematopoietic stem cell transplantation in autoimmune diseases].

    PubMed

    Albarracín, Flavio; López Meiller, María José; Naswetter, Gustavo; Longoni, Héctor

    2008-01-01

    Transplantation of hematopoietic stem cells, which are capable of self renewal and reconstitution of all types of blood cells, can be a treatment for numerous potential lethal diseases, including leukemias and lymphomas. It may now be applicable for the treatment of severe autoimmune diseases, such as therapy-resistant multiple sclerosis, lupus and systemic sclerosis. Studies in animal models show that the transfer of hematopoietic stem cells can reverse autoimmunity. The outcome of ongoing clinical trials, as well as of studies in patients and animal models, will help to determine the role that stem-cell transplantation can play in the treatment of autoimmune diseases.

  8. Post-transplant lymphoproliferative disease after allogeneic hematopoietic stem cell transplantation: a single-center experience.

    PubMed

    Luo, Lan; Zhang, Lin; Cai, Bo; Li, Honghua; Huang, Wenrong; Jing, Yu; Zhu, Haiyan; Zhao, Yu; Bo, Jian; Wang, Quanshun; Han, Xiaoping; Yu, Li; Gao, Chunji

    2014-01-08

    Post-transplant lymphoproliferative disease (PTLD) is a rare and serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) or solid organ transplantation. We conducted a retrospective analysis of the occurrence of post-transplant lymphoproliferative disease in allo-HSCT recipients over 12 years in a single center in China. A total of 343 patients received allo-HSCT. The conditioning therapy consisted of a busulfan/cyclophosphamide-based regimen, a fludarabine/cyclophosphamide-based regimen, or total-body irradiation and cyclophosphamide. In transplantations from unrelated donors and haplo-identical donors, patients also received antithymocyte globulin (ATG) or thymoglobulin as part of the conditioning. Five of the 343 patients (1.46%) were diagnosed with PTLD and all 5 were given ATG as part of conditioning. Among these 5 patients, 4 had lymphoid neoplasm before transplantation. EBV-positivity was confirmed in 4 patients. All 5 PTLD patients received reduction of immunosuppression (RI) as fundamental therapy. At follow-up on April 1, 2013, 1 patient had survived for 2 years and 1 had survived for 9 years. The correlation of PTLD with ATG and underlying diseases were examined by statistical analysis using the chi-squared test or Fisher's exact test (P=0.011 and 0.025, respectively). Although only 1.46% of patients progressed to PTLD associated with ATG and underlying diseases, the mortality was still high. Moreover, RI can be an effective therapy for PTLD patients, but other approaches should be further explored.

  9. Immunosuppressive Total Lymphoid Irradiation-Based Reconditioning Regimens Enable Engraftment After Graft Rejection or Graft Failure in Patients Treated With Allogeneic Hematopoietic Stem Cell Transplantation

    SciTech Connect

    Heinzelmann, Frank; Lang, Peter J.; Ottinger, Hellmut; Faul, Christoph; Bethge, Wolfgang; Handgretinger, Rupert; Bamberg, Michael; Belka, Claus

    2008-02-01

    Purpose: To retrospectively evaluate the efficacy of total lymphoid irradiation (TLI)-based reconditioning regimens in patients with graft failure or graft rejection after allogeneic hematopoietic stem cell transplantation. Methods and Materials: The results of 14 patients (7 adults and 7 children) with a variety of hematologic malignant diseases treated with a TLI-based reconditioning regimen with 7-Gy single-dose application plus anti-T-lymphocyte antibody OKT3 (n = 11) and/or antithymocyte globulin (n = 7)/fludarabine (n = 9), followed by an infusion of peripheral blood stem cells (n = 13) or bone marrow stem cells (n = 1) from related or unrelated donors, were retrospectively analyzed. Results: Of the 14 recipients, the data from 11 were evaluable for engraftment after TLI-based reconditioning because 3 adults died early (at Day 2, 5, and 15) after the second transplantation of infectious complications. Engraftment in 4 adults was seen after a median of 12 days (range, 10-18) and occurred after a median of 10 days (range, 9-32) in the 7 children. TLI-based reconditioning was well-tolerated with no severe toxicity. The median overall survival and disease-free survival for the whole cohort was 140 days (range, 5-1,268). After a median follow-up of 681 days, the disease-free survival and overall survival rate was 85.7% and 85.7%, respectively, in the children. Despite engraftment in the 4 remaining adults, 1 died of fatal graft-vs.-host disease, 1 of infectious complications, 1 of disease relapse, and 1 of acute respiratory distress syndrome. Conclusions: In patients with graft failure or graft rejection after allogeneic hematopoietic stem cell transplantation, TLI-based reconditioning regimens allow sustained engraftment, paralleled by a favorable toxicity profile, potentially leading to long-term survival.

  10. Combined transplantation of human mesenchymal stem cells and human retinal progenitor cells into the subretinal space of RCS rats.

    PubMed

    Qu, Linghui; Gao, Lixiong; Xu, Haiwei; Duan, Ping; Zeng, Yuxiao; Liu, Yong; Yin, Zheng Qin

    2017-03-15

    Retinitis pigmentosa (RP) is one of hereditary retinal diseases characterized by the loss of photoreceptors. Cell transplantation has been clinically applied to treat RP patients. Human retinal progenitor cells (HRPCs) and human bone marrow-derived mesenchymal stem cells (HBMSCs) are the two commonly and practically used stem cells for transplantation. Since combined transplantation could be a promising way to integrate the advantages of both stem cell types, we transplanted HRPCs and HBMSCs into the subretinal space (SRS) of Royal College of Surgeons (RCS) rats. We report that HRPCs/HBMSCs combined transplantation maintains the electroretinogram results much better than HRPCs or HBMSCs single transplantations. The thickness of outer nuclear layer also presented a better outcome in the combined transplantation. Importantly, grafted cells in the combination migrated better, both longitudinally and latitudinally, than single transplantation. The photoreceptor differentiation of grafted cells in the retina of RCS rats receiving combined transplantation also showed a higher ratio than single transplantation. Finally, activation of microglia and the gliosis of Müller cells were more effectively suppressed in combined transplantation, indicating better immunomodulatory and anti-gliosis effects. Taken together, combining the transplantation of HRPCs and HBMSCs is a more effective strategy in stem cell-based therapy for retinal degenerative diseases.

  11. Stem cell transplantation for treatment of sickle cell disease: bone marrow versus cord blood transplants.

    PubMed

    Thompson, Lisa Marie; Ceja, Maria Estela; Yang, Sonal Patel

    2012-08-01

    The transplantation of stem cells harvested from bone marrow and cord blood for the treatment of sickle cell disease (SCD) is reviewed. Current treatment options have lengthened the lifespan of patients with SCD. Hydroxyurea is the standard of care for the management of SCD, but it does not prevent serious complications in all patients. For those patients with severe disease, stem cell transplantation may be an appropriate curative option. However, less than one third of these patients find an appropriate matched related bone marrow donor. Cord blood offers a more readily available source of stem cells for transplantation. Donor morbidity is eliminated, since the cells come from banked cords, and the harvesting process is noninvasive for the donor. Another advantage of cord blood transplantation is the lower occurrence of graft-versus-host disease (GVHD). One disadvantage of transplantation with cord blood includes delayed time to engraftment. Due to the mortality associated with stem cell transplantation, it may be most appropriate to reserve the procedure for patients who have a more severe course of SCD. Although bone marrow, peripheral blood, and cord blood transplantation has been successfully performed in patients with SCD, data remain limited regarding the optimal preparative regimens, the most appropriate stem cell source, and the type of GVHD prophylaxis to be used after transplantation. More data are warranted before this treatment approach can be recommended as a standard of care for SCD.

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

    PubMed

    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.

  13. Stem cell transplantation outcomes in lymphoblastic lymphoma.

    PubMed

    Brammer, Jonathan E; Khouri, Issa; Marin, David; Ledesma, Celina; Rondon, Gabriela; Ciurea, Stefan O; Nieto, Yago; Champlin, Richard E; Hosing, Chitra; Kebriaei, Partow

    2017-02-01

    Lymphoblastic lymphoma (LBL) is an aggressive lymphoma pathologically similar to lymphoblastic leukemia, but primarily presents with nodal or extra-medullary involvement. The aim of this study is to describe outcomes of patients undergoing stem cell transplantation (SCT) for LBL compared to historical data. Thirty-nine patients, of which 54% lacked complete remission (CR), received SCT for LBL between 1990 and 2015; 31 allogeneic and eight autologous. Overall survival (OS) and progression free survival (PFS) at three years for the entire cohort was 41%, the cumulative incidence (CI) of non-relapse mortality (NRM) was 18% at one year, and CI relapse mortality was 28% at one-year and 36% at three years; results similar to historical reports. On multivariate analysis, the use of total-body irradiation (TBI) based conditioning and transplantation in CR were independently predictive of OS and PFS. For patients requiring SCT for LBL, CR and TBI-based conditioning prior to allogeneic SCT may provide improved disease control.

  14. Consideration of strategies for hematopoietic cell transplantation.

    PubMed

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

    2009-01-01

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

  15. Genetic modification of cells for transplantation.

    PubMed

    Lai, Yi; Drobinskaya, Irina; Kolossov, Eugen; Chen, Chunguang; Linn, Thomas

    2008-01-14

    Progress in gene therapy has produced promising results that translate experimental research into clinical treatment. Gene modification has been extensively employed in cell transplantation. The main barrier is an effective gene delivery system. Several viral vectors were utilized in end-stage differentiated cells. Recently, successful applications were described with adenovirus-associated vectors. As an alternative, embryonic stem cell- and stem cell-like systems were established for generation of tissue-specified gene-modified cells. Owing to the feasibility for genetic manipulations and the self-renewing potency of these cells they can be used in a way enabling large-scale in vitro production. This approach offers the establishment of in vitro cell culture systems that will deliver sufficient amounts of highly purified, immunoautologous cells suitable for application in regenerative medicine. In this review, the current technology of gene delivery systems to cells is recapitulated and the latest developments for cell transplantation are discussed.

  16. Reduced platelet transfusions and earlier platelet engraftment using alemtuzumab-based conditioning regimen in allogeneic stem cell transplantation.

    PubMed

    Neumann, Thomas; Schneidewind, Laila; Thiele, Thomas; Schulze, Meike; Klenner, Anne F; Busemann, Christoph; Pink, Daniel; Greinacher, Andreas; Dölken, Gottfried; Krüger, William H

    2016-05-01

    In patients undergoing allogeneic stem cell transplantation, conditioning regimens containing alemtuzumab instead of anti-thymocyte globulin (ATG) may result in an earlier platelet engraftment and a reduced number of platelet transfusions. We performed a retrospective, single-center, case-control study analyzing time to engraftment and transfusion needs using alemtuzumab in comparison with ATG as part of conditioning protocol. Median values for time to platelet engraftment, number of transfused platelet concentrates and number of transfused red cell concentrates were 12 versus 19.5 days (p < 0.001), 2 versus 14 (p < 0.001) and 6 versus 14.5 (p = 0.003) in the alemtuzumab and ATG group. Time to leukocyte engraftment did not differ with median 15 days in both groups. Patients in the ATG group showed a significant higher decrease in platelet count during conditioning (68 vs. 29 %, p = 0.001), leading to significant lower median platelet counts at the day of stem cell infusion (38 vs. 95.5 Gpt/l, p = 0.008), and higher values for median C-reactive protein after first antibody infusion (69.0 vs. 43.6 mg/l, p = 0.001) compared with alemtuzumab group. Test for significance was done by using Wilcoxon rank-sum test. Subgroup analysis considering the type of ATG used (Thymoglobulin vs. ATG Fresenius) revealed that differences between alemtuzumab and ATG group were more due to effects of ATG Fresenius than Thymoglobulin. The use of alemtuzumab in comparison with ATG as part of the conditioning regimen may be an approach to reduce the number of transfused platelet and red cell concentrates after allogeneic stem cell transplantation.

  17. In Utero Haematopoietic Stem Cell Transplantation (IUHSCT)

    PubMed Central

    Renda, Maria Concetta; Maggio, Aurelio

    2009-01-01

    In utero haematopoietic stem cell transplantation (IUHSCT) is a non-myeloablative approach for the prenatal treatment of genetic disorders. However, in target disorders, where there is not a selective advantage for donor cells, a useful donor-cell chimerism has not been achieved. There are three possible barriers to engraftment following IUHSCT: limited space in the fetus due to host-cell competition; the large number of donor cells needed, and the immunological asset of recipient. PMID:21415998

  18. In Utero Haematopoietic Stem Cell Transplantation (IUHSCT).

    PubMed

    Renda, Maria Concetta; Maggio, Aurelio

    2009-12-29

    In utero haematopoietic stem cell transplantation (IUHSCT) is a non-myeloablative approach for the prenatal treatment of genetic disorders. However, in target disorders, where there is not a selective advantage for donor cells, a useful donor-cell chimerism has not been achieved. There are three possible barriers to engraftment following IUHSCT: limited space in the fetus due to host-cell competition; the large number of donor cells needed, and the immunological asset of recipient.

  19. Synthetic Biology in Cell and Organ Transplantation.

    PubMed

    Stevens, Sean

    2017-02-01

    The transplantation of cells and organs has an extensive history, with blood transfusion and skin grafts described as some of the earliest medical interventions. The speed and efficiency of the human immune system evolved to rapidly recognize and remove pathogens; the human immune system also serves as a barrier against the transplant of cells and organs from even highly related donors. Although this shows the remarkable effectiveness of the immune system, the engineering of cells and organs that will survive in a host patient over the long term remains a steep challenge. Progress in the understanding of host immune responses to donor cells and organs, combined with the rapid advancement in synthetic biology applications, allows the rational engineering of more effective solutions for transplantation. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

  20. Magnetic resonance imaging of transplanted stem cell fate in stroke.

    PubMed

    Aghayan, Hamid Reza; Soleimani, Masoud; Goodarzi, Parisa; Norouzi-Javidan, Abbas; Emami-Razavi, Seyed Hasan; Larijani, Bagher; Arjmand, Babak

    2014-05-01

    Nowadays, scientific findings in the field of regeneration of nervous system have revealed the possibility of stem cell based therapies for damaged brain tissue related disorders like stroke. Furthermore, to achieve desirable outcomes from cellular therapies, one needs to monitor the migration, engraftment, viability, and also functional fate of transplanted stem cells. Magnetic resonance imaging is an extremely versatile technique for this purpose, which has been broadly used to study stroke and assessment of therapeutic role of stem cells. In this review we searched in PubMed search engine by using following keywords; "Stem Cells", "Cell Tracking", "Stroke", "Stem Cell Transplantation", "Nanoparticles", and "Magnetic Resonance Imaging" as entry terms and based on the mentioned key words, the search period was set from 1976 to 2012. The main purpose of this article is describing various advantages of molecular and magnetic resonance imaging of stem cells, with focus on translation of stem cell research to clinical research.

  1. Stem cell transplantation reverses chemotherapy-induced cognitive dysfunction

    PubMed Central

    Acharya, Munjal M.; Martirosian, Vahan; Chmielewski, Nicole N.; Hanna, Nevine; Tran, Katherine K.; Liao, Alicia C.; Christie, Lori-Ann; Parihar, Vipan K.; Limoli, Charles L.

    2014-01-01

    The frequent use of chemotherapy to combat a range of malignancies can elicit severe cognitive dysfunction often referred to as “chemobrain”, a condition that can persist long after the cessation of treatment in as many as 75% of survivors. While cognitive health is a critical determinant of therapeutic outcome, chemobrain remains an unmet medical need that adversely impacts quality of life in pediatric and adult cancer survivors. Using a rodent model of chemobrain, we showed that chronic cyclophosphamide treatment induced significant performance based decrements on behavioral tasks designed to interrogate hippocampal and cortical function. Intrahippocampal transplantation of human neural stem cells resolved all cognitive impairments when animals were tested one month after the cessation of chemotherapy. In transplanted animals, grafted cells survived (8%) and differentiated along neuronal and astroglial lineages, where improved cognition was associated with reduced neuroinflammation and enhanced host dendritic arborization. Stem cell transplantation significantly reduced the number of activated microglia after cyclophosphamide treatment in the brain. Granule and pyramidal cell neurons within the dentate gyrus and CA1 subfields of the hippocampus exhibited significant reductions in dendritic complexity, spine density, immature and mature spine types following chemotherapy, adverse effects that were eradicated by stem cell transplantation. Our findings provide the first evidence that cranial transplantation of stem cells can reverse the deleterious effects of chemobrain, through a trophic support mechanism involving the attenuation of neuroinflammation and the preservation host neuronal architecture. PMID:25687405

  2. Cell transplantation therapy for spinal cord injury.

    PubMed

    Assinck, Peggy; Duncan, Greg J; Hilton, Brett J; Plemel, Jason R; Tetzlaff, Wolfram

    2017-04-25

    Spinal cord injury can lead to severe motor, sensory and autonomic dysfunction. Currently, there is no effective treatment for the injured spinal cord. The transplantation of Schwann cells, neural stem cells or progenitor cells, olfactory ensheathing cells, oligodendrocyte precursor cells and mesenchymal stem cells has been investigated as potential therapies for spinal cord injury. However, little is known about the mechanisms through which these individual cell types promote repair and functional improvements. The five most commonly proposed mechanisms include neuroprotection, immunomodulation, axon regeneration, neuronal relay formation and myelin regeneration. A better understanding of the mechanisms whereby these cells promote functional improvements, as well as an appreciation of the obstacles in implementing these therapies and effectively modeling spinal cord injury, will be important to make cell transplantation a viable clinical option and may lead to the development of more targeted therapies.

  3. Recent advances in hematopoietic stem cell transplantation.

    PubMed

    Norkin, Maxim; Wingard, John R

    2017-01-01

    Hematopoietic cell transplantation (HCT), once used as a last-resort therapy, is now considered a lifesaving procedure for thousands of patients with life-threatening diseases worldwide and is frequently used early in the course of treatment for diseases destined to be uncontrollable by non-HCT therapies. Incremental advances leading to reduction of post-transplant morbidity and mortality by better control of graft versus host disease (GVHD), infections, and regimen-related toxicities, coupled with greater donor options, not only significantly increased the utilization and success of this procedure but also allowed many of these patients to enjoy healthy and productive lives after HCT. Emerging concepts in the field are now focused on the expansion of available donor options, further reduction of transplant-related toxicity, and decrease in post-transplant relapse.

  4. Recent advances in hematopoietic stem cell transplantation

    PubMed Central

    Norkin, Maxim; Wingard, John R

    2017-01-01

    Hematopoietic cell transplantation (HCT), once used as a last-resort therapy, is now considered a lifesaving procedure for thousands of patients with life-threatening diseases worldwide and is frequently used early in the course of treatment for diseases destined to be uncontrollable by non-HCT therapies. Incremental advances leading to reduction of post-transplant morbidity and mortality by better control of graft versus host disease (GVHD), infections, and regimen-related toxicities, coupled with greater donor options, not only significantly increased the utilization and success of this procedure but also allowed many of these patients to enjoy healthy and productive lives after HCT. Emerging concepts in the field are now focused on the expansion of available donor options, further reduction of transplant-related toxicity, and decrease in post-transplant relapse. PMID:28663793

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

    PubMed

    Van Pham, Phuc

    2016-04-27

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

  6. Genetic Modification of Stem Cells for Transplantation

    PubMed Central

    Phillips, M. Ian; Tang, Yao Liang

    2009-01-01

    Gene modification of cells for prior to their transplantation, especially stem cells, enhances their survival and increases their function in cell therapy. Like the Trojan horse, the gene modified cell has to gain entrance inside the host’s walls and survive and deliver its transgene products Using cellular, molecular and gene manipulation techniques the transplanted cell can be protected in a hostile environment from immune rejection, inflammation, hypoxia and apoptosis. Genetic engineering to modify cells involves constructing modules of functional gene sequences. They can be simple reporter genes or complex cassettes with gene switches, cell specific promoters and multiple transgenes. We discuss methods to deliver and construct gene cassettes with viral and non viral delivery, siRNA, and conditional Cre/Lox P. We review the current uses of gene modified stem cells in cardiovascular disease, diabetes, neurological diseases,( including Parkinson’s, Alzheimer’s and spinal cord injury repair), bone defects, hemophilia, and cancer. PMID:18031863

  7. Genetic modification of stem cells for transplantation.

    PubMed

    Phillips, M Ian; Tang, Yao Liang

    2008-01-14

    Gene modification of cells prior to their transplantation, especially stem cells, enhances their survival and increases their function in cell therapy. Like the Trojan horse, the gene-modified cell has to gain entrance inside the host's walls and survive and deliver its transgene products. Using cellular, molecular and gene manipulation techniques the transplanted cell can be protected in a hostile environment from immune rejection, inflammation, hypoxia and apoptosis. Genetic engineering to modify cells involves constructing modules of functional gene sequences. They can be simple reporter genes or complex cassettes with gene switches, cell specific promoters and multiple transgenes. We discuss methods to deliver and construct gene cassettes with viral and non-viral delivery, siRNA, and conditional Cre/Lox P. We review the current uses of gene-modified stem cells in cardiovascular disease, diabetes, neurological diseases, (including Parkinson's, Alzheimer's and spinal cord injury repair), bone defects, hemophilia, and cancer.

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

    PubMed

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

    2012-08-21

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

  9. Bone marrow transplant - discharge

    MedlinePlus

    Transplant - bone marrow - discharge; Stem cell transplant - discharge; Hematopoietic stem cell transplant - discharge; Reduced intensity; Non-myeloablative transplant - discharge; Mini transplant - discharge; Allogenic bone marrow transplant - ...

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

    PubMed

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

    2015-10-27

    Allogeneic stem cell transplantation (alloSCT) represents a curative therapeutic option for patients with myelodysplastic syndrome (MDS), but relapse and non-relapse mortality (NRM) limit treatment efficacy. Based on our previous observation in acute myeloid leukemia we investigated the impact of pre-transplant weight loss on post-transplant outcome in MDS patients. A total of 111 patients diagnosed with MDS according to WHO criteria transplanted between 2000 and 2012 in three different transplant centers were included into the analysis. Data on weight loss were collected from medical records prior to conditioning therapy and 3-6 months earlier. Patient, disease and transplant characteristics did not differ between patients with weight loss (2-5%, n = 17; > 5%, n = 17) and those without (n = 77). In a mixed effect model, weight loss was associated with higher risk MDS (p = 0.046). In multivariable analyses, pre-transplant weight loss exceeding 5% was associated with a higher incidence of relapse (p < 0.001) and NRM (p = 0.007). Pre-transplant weight loss of 2-5% and > 5% were independent predictors of worse disease-free (p = 0.023 and p < 0.001, respectively) and overall survival (p = 0.043 and p < 0.001, respectively). Our retrospective study suggests that MDS patients losing weight prior to alloSCT have an inferior outcome after transplantation. Prospective studies addressing pre-transplant nutritional interventions are highly warranted.

  11. Childhood Hematopoietic Cell Transplantation (PDQ®)—Health Professional Version

    Cancer.gov

    Blood and bone marrow transplantation involves the infusion of blood stem cells into a patient to reconstitute the blood system. Learn about transplant types, cell selection, and short- and long-term complications in this expert-reviewed summary.

  12. Haploidentical hematopoietic stem cell transplantation with a megadose T-cell-depleted graft: harnessing natural and adaptive immunity.

    PubMed

    Aversa, Franco; Martelli, Massimo F; Velardi, Andrea

    2012-12-01

    For patients with high-risk acute leukemia who do not have a matched donor or who urgently need a transplant, transplantation from a full human leukocyte antigen (HLA) haplotype mismatched family donor should be considered a viable option. Clinical trials have shown that a strategy for haploidentical transplantation based on the infusion of high numbers of T-cell-depleted hematopoietic progenitor cells and no post-transplant immunosuppression controls bi-directional T-cell alloreactivity, ie, graft rejection and graft-versus-host disease (GvHD) in patients with leukemia. Overall, event-free survival compares favorably with reports of transplants using sources of stem cells other than the matched sibling. This transplant modality has highlighted the crucial role of donor-versus-recipient natural killer cell (NK) alloreactivity in the control of leukemia relapse. Current studies are focusing on rebuilding post-transplant immunity to improve clinical outcomes.

  13. Nonmyeloablative allogeneic hematopoietic cell transplantation

    PubMed Central

    Storb, Rainer; Sandmaier, Brenda M.

    2016-01-01

    Most hematological malignancies occur in older patients. Until recently these patients and those with comorbidities were not candidates for treatment with allogeneic hematopoietic transplantation because they were unable to tolerate the heretofore used high-dose conditioning regimens. The finding that many of the cures achieved with allogeneic hematopoietic transplantation were due to graft-versus-tumor effects led to the development of less toxic and well-tolerated reduced intensity and nonmyeloablative regimens. These regimens enabled allogeneic engraftment, thereby setting the stage for graft-versus-tumor effects. This review summarizes the encouraging early results seen with the new regimens and discusses the two hurdles that need to be overcome for achieving even greater success, disease relapse and graft-versus-host disease. PMID:27132278

  14. Emergent Complications in the Pediatric Hematopoietic Stem Cell Transplant Patient

    PubMed Central

    Munchel, Ashley; Chen, Allen; Symons, Heather

    2014-01-01

    Hematopoietic cell transplantation is the only potentially curative option for a variety of pediatric malignant and nonmalignant disorders. Despite advances in transplantation biology and immunology as well as in posttransplant management that have contributed to improved survival and decreased transplant-related mortality, hematopoietic cell transplantation does not come without significant risk of complications. When patients who have undergone hematopoietic cell transplantation present to the emergency department, it is important to consider a variety of therapy-related complications to optimize management and outcome. In this article, we use clinical cases to highlight some of the more common emergent complications after hematopoietic cell transplantation. PMID:25411564

  15. Role of hematopoietic stem cell transplantation in multiple myeloma.

    PubMed

    Garcia, Ima N

    2015-02-01

    High-dose therapy followed by autologous stem cell transplantation (ASCT) has been the standard frontline consolidative therapy for patients with newly diagnosed multiple myeloma (MM) for > 2 decades. This approach has resulted in higher complete response (CR) rates and increased event-free survival and overall survival (OS) compared with conventional chemotherapy. The emergence of novel agent-based therapy combined with ASCT has revolutionized MM therapy by improving the CR rates and OS, raising questions concerning the role of hematopoietic stem cell transplantation in this setting.

  16. Bacterial foodborne infections after hematopoietic cell transplantation.

    PubMed

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

    2014-11-01

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

  17. Hematopoietic stem cell transplantation for sickle cell anemia.

    PubMed

    Vermylen, C; Cornu, G

    1997-11-01

    Hematopoietic stem cell transplantation is the only therapy able to cure sickle cell anemia at the present time. So far, transplantations have been undertaken in approximatively 140 sickle cell patients all over the world, with good results. The selection of patients for transplantation remains a subject of dilemma because of the unpredictable course of the disease and the lack of valuable prognostic markers. The selection criteria accepted so far concern young patients under the age of 16, with a morbid course of the disease and having a HLA-compatible sibling. In Belgium, patients going back to their country of origin were also considered for transplantation. For 100 patients who underwent transplantation in Europe, the current Kaplan-Meier estimates of overall survival, event-free survival, and disease-free survival rates are 90%, 79%, and 81%, respectively. Benefits and side effects are analyzed.

  18. Late Cardiovascular Complications after Hematopoietic Cell Transplantation

    PubMed Central

    Chow, Eric J.; Wong, Kenneth; Lee, Stephanie J.; Cushing-Haugen, Kara L.; Flowers, Mary E.D.; Friedman, Debra L.; Leisenring, Wendy M.; Martin, Paul J.; Mueller, Beth A.; Baker, K. Scott

    2014-01-01

    PURPOSE To better understand the combined effects of pre-transplant, transplant, and post-transplant factors in determining risks of serious cardiovascular disease following hematopoietic cell transplantation (HCT). METHODS Hospitalizations and deaths associated with serious cardiovascular outcomes were identified among 1,379 Washington State residents who received HCT (57% allogeneic; 43% autologous) at a single center from 1985–2005, survived ≥2 years, and followed through 2008. Using a nested-case-cohort design, relationships (hazard ratios, HR) between potential risk factors and outcomes were examined among affected survivors and a randomly selected sub-cohort (n=509). RESULTS After 7.0 years median follow-up (range 2.0–23.7), the 10-year cumulative incidence of ischemic heart disease, cardiomyopathy, stroke, and all-cause cardiovascular death was 3.8%, 6.0%, 3.5%, and 3.7%, respectively. In multivariable analysis, increased pre-transplant anthracyclines was associated with cardiomyopathy. Active chronic graft vs. host disease was associated with cardiovascular death (HR 4.0, 95% CI 1.1–14.7); risk was otherwise similar between autologous vs. allogeneic HCT recipients. Independent of therapeutic exposures, pre-transplant smoking, hypertension, dyslipidemia, diabetes, and obesity conferred additional risk of all outcomes except stroke (HR ≥1.5 for each additional risk factor, p<0.03). Hypertension and dyslipidemia at one year with persistence of these conditions two or more years following HCT also were associated with independent risks of multiple outcomes. CONCLUSION Hematopoietic cell transplant survivors with pre-existing or newly developed and persistent cardiovascular risk factors remain at greater risk of subsequent serious cardiovascular disease compared with other survivors, independent of chemo- and radiotherapy exposures. These survivors should receive appropriate follow-up and be considered for primary intervention. PMID:24565992

  19. Successful T-cell-depleted haploidentical hematopoietic stem cell transplantation in a child with dyskeratosis congenita after a fludarabine-based conditioning regimen.

    PubMed

    Algeri, Mattia; Comoli, Patrizia; Strocchio, Luisa; Perotti, Cesare; Corbella, Franco; Del Fante, Claudia; Baio, Ambrogia; Giorgiani, Giovanna; Gurrado, Antonella; Accornero, Elisa; Cugno, Chiara; Pession, Andrea; Zecca, Marco

    2015-05-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) is the only cure for marrow failure associated with dyskeratosis congenita (DC). Data on transplants from alternative donors are limited. We describe a boy with DC and severe aplastic anemia who underwent haploidentical T-cell depleted HSCT using a reduced-intensity conditioning regimen. He underwent engraftment without toxicity or GVHD. His posttransplant course was complicated by EBV reactivation, treated with rituximab and EBV-specific T lymphocytes. After 26 months, he is in complete chimerism, with normal blood count and no sign of GVHD or pulmonary dysfunction. To the best of our knowledge, this is the first report of DC successfully treated with allogeneic HSCT from a haploidentical family donor.

  20. Hemopoietic cell transplantation for myelodysplastic syndromes.

    PubMed

    Benesch, Martin; Deeg, H Joachim

    2003-05-01

    Myelodysplastic syndromes are clonal stem cell disorders, and allogeneic hemopoietic cell transplantation (HCT) is the only therapy with curative potential. Among patients with less-advanced myelodysplastic syndromes, 3-year survivals of 65% to 75% are achievable with human leukocyte antigen (HLA)-identical related and HLA-matched unrelated donors. The probability of relapse is less than 5%. Among patients with advanced disease (> or = 5% marrow blasts), 35% to 45% and 25% to 30%, respectively, are surviving in remission after transplantation from related or unrelated donors. The incidence of post-transplant relapse is 10% to 35%. Criteria of the International Prognostic Scoring System, originally developed for nontransplanted patients, also predict relapse and survival after HCT. Refined conditioning regimens have permitted successful HCT even in patients in their seventh decade of life. Results with a regimen using a combination of busulfan (targeted to predetermined plasma levels) and cyclophosphamide are particularly encouraging. Improved survival with transplants from unrelated volunteer donors reflects selection of donors on the basis of high-resolution (allele-level) HLA typing. Nevertheless, transplant-related morbidity and mortality, including graft-versus-host disease, remain challenges that need to be addressed with innovative approaches. Some patients who achieve a chemotherapy-induced complete remission may also benefit from autologous HCT.

  1. Detection of Herpesviridae in whole blood by multiplex PCR DNA-based microarray analysis after hematopoietic stem cell transplantation.

    PubMed

    Debaugnies, France; Busson, Laurent; Ferster, Alina; Lewalle, Philippe; Azzi, Nadira; Aoun, Mickael; Verhaegen, Godelieve; Mahadeb, Bhavna; de Marchin, Jérôme; Vandenberg, Olivier; Hallin, Marie

    2014-07-01

    Viral infections are important causes of morbidity and mortality in patients after hematopoietic stem cell transplantation. The monitoring by PCR of Herpesviridae loads in blood samples has become a critical part of posttransplant follow-up, representing mounting costs for the laboratory. In this study, we assessed the clinical performance of the multiplex PCR DNA microarray Clart Entherpex kit for detection of cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human herpesvirus 6 (HHV-6) as a screening test for virological follow-up. Two hundred fifty-five blood samples from 16 transplanted patients, prospectively tested by routine PCR assays, were analyzed by microarray. Routine PCR detected single or multiple viruses in 42% and 10% of the samples, respectively. Microarray detected single or multiple viruses in 34% and 18% of the samples, respectively. Microarray results correlated well with CMV and EBV detections by routine PCR (kappa tests = 0.79 and 0.78, respectively), whereas a weak correlation was observed with HHV-6 (0.43). HHV-7 was also detected in 48 samples by microarray. In conclusion, the microarray is a reliable screening assay for a posttransplant virological follow-up to detect CMV and EBV infections in blood. However, positive samples must be subsequently confirmed and viral loads must be quantified by PCR assays. Limitations were identified regarding HHV-6 detection. Although it is promising, is easy to use as a first-line test, and allows a reduction in the cost of analysis without undue delay in the reporting of the final quantitative result to the clinician, some characteristics of this microarray should be improved, particularly regarding quality control and the targeted virus panel, such that it could then be used as a routine test. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  2. Autologous stem cell transplantation for systemic sclerosis.

    PubMed

    Farge, Dominique; Nash, Richard; Laar, Jacob M

    2008-12-01

    Systemic sclerosis (SSc) is a generalised autoimmune disease, of yet unknown origin, with two major clinical subsets: the limited (lcSSc) and the diffuse cutaneous (dcSSc) forms, which can be distinguished by the extent of skin involvement, the autoantibody profile and the pattern of organ involvement. With an incidence of 1/10(5), SSc affects around 250,000 people in Europe and is responsible for significant morbidity with a 5-year mortality rate of at least 30% of all patients. In patients with rapidly progressive dcSSc, the 5-year mortality is estimated to be 40-50%. Hematopoietic stem cell transplantation (HSCT), mostly autologous but also allogeneic in some specific cases, has been employed worldwide since 1996 as a new therapeutic strategy in patients with a poor prognosis. In 2007, 150 HSCT procedures have been reported in the EBMT data base. We review herein both the short and the long-term reports from the various European and North American phase I-II studies, which have shown that autologous HSCT in selected patients with severe dcSSc results in sustained improvement of skin thickening and stabilisation of organ function up to seven years after transplantation. Based on these promising results, ongoing phase III trials have been designed in parallel, both in Europe (ASTIS) and in North America (SCOTT) aiming to analyse the respective benefits from autologous HSCT respectively without or with high dose irradiation. This review reports the current data concerning the effects of HSCT on survival, skin, and major organ function in patients with severe dcSSc.

  3. Progress in hematopoietic stem cell transplantation as allogeneic cellular gene therapy in thalassemia.

    PubMed

    Isgrò, Antonella; Gaziev, Javid; Sodani, Pietro; Lucarelli, Guido

    2010-08-01

    Allogeneic hemopoietic stem cell transplantation (HSCT) represents one of the best cures for thalassemia. Currently, HSCT for thalassemia consists of allogeneic stem cell gene therapy and still awaits autologous genetically modified stem cell transplantation. HSCT for thalassemia has substantially improved over the last two decades, due in large part to improvements in preventive strategies, the effective control of transplant-related complications, and the development of new preparative regimens. A risk classes-based approach to transplantation in thalassemia has led to disease-free survival probability of 87, 85, and 80% in classes 1, 2, and 3 patients, respectively. Adult thalassemia patients, who are higher risk patients for transplant-related toxicity due to an advanced phase of the disease, have a cure rate of 65% with current treatment protocol. Patients who do not have matched family or unrelated donors could benefit from haploidentical mother-to-child transplantation. Overall, the results of this type of transplantation appear encouraging.

  4. Monocyte-Derived Suppressor Cells in Transplantation.

    PubMed

    Ochando, Jordi; Conde, Patricia; Bronte, Vincenzo

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

  5. Human Retinal Progenitor Cell Transplantation Preserves Vision*

    PubMed Central

    Luo, Jing; Baranov, Petr; Patel, Sherrina; Ouyang, Hong; Quach, John; Wu, Frances; Qiu, Austin; Luo, Hongrong; Hicks, Caroline; Zeng, Jing; Zhu, Jing; Lu, Jessica; Sfeir, Nicole; Wen, Cindy; Zhang, Meixia; Reade, Victoria; Patel, Sara; Sinden, John; Sun, Xiaodong; Shaw, Peter; Young, Michael; Zhang, Kang

    2014-01-01

    Cell transplantation is a potential therapeutic strategy for retinal degenerative diseases involving the loss of photoreceptors. However, it faces challenges to clinical translation due to safety concerns and a limited supply of cells. Human retinal progenitor cells (hRPCs) from fetal neural retina are expandable in vitro and maintain an undifferentiated state. This study aimed to investigate the therapeutic potential of hRPCs transplanted into a Royal College of Surgeons (RCS) rat model of retinal degeneration. At 12 weeks, optokinetic response showed that hRPC-grafted eyes had significantly superior visual acuity compared with vehicle-treated eyes. Histological evaluation of outer nuclear layer (ONL) characteristics such as ONL thickness, spread distance, and cell count demonstrated a significantly greater preservation of the ONL in hRPC-treated eyes compared with both vehicle-treated and control eyes. The transplanted hRPCs arrested visual decline over time in the RCS rat and rescued retinal morphology, demonstrating their potential as a therapy for retinal diseases. We suggest that the preservation of visual acuity was likely achieved through host photoreceptor rescue. We found that hRPC transplantation into the subretinal space of RCS rats was well tolerated, with no adverse effects such as tumor formation noted at 12 weeks after treatment. PMID:24407289

  6. Retinal stem cells and potential cell transplantation treatments.

    PubMed

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

    2014-11-01

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

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

    PubMed

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

    2010-12-01

    SOT may be indicated for a select group of pediatric patients who experience permanent organ failure following HSCT. However, there is limited information available about outcomes. We identified eight children at our center who received an SOT following an HSCT. Patients were six months to 18 yr at HSCT. Diseases for which children underwent HSCT included thalassemia, Wiskott-Aldrich syndrome, Shwachman-Diamond/bone marrow failure, sickle cell disease (SCD), erythropoietic porphyria (EP), ALL, chronic granulomatous disease, and neuroblastoma. Time from HSCT to SOT was 13 days to seven yr (median, 27 months. Lung SOT was performed for two patients with BO, kidney transplants for three patients, and liver transplants for three patients (VOD, chronic GVHD). Seven patients are alive with functioning allografts 6-180 months from SOT. Advances in organ procurement, operative technique, immunosuppressant therapy, and infection control may allow SOT for a select group of patients post-HSCT. However, scarcity of donor organs available in a timely fashion continues to be a limiting factor. Children who have undergone HSCT and develop single organ failure should be considered for an SOT if there is a high likelihood of cure of the primary disease. © 2010 John Wiley & Sons A/S.

  8. Limbal stem cell transplantation: current perspectives

    PubMed Central

    Atallah, Marwan Raymond; Palioura, Sotiria; Perez, Victor L; Amescua, Guillermo

    2016-01-01

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

  9. Allogeneic stem cell transplantation for elderly patients with myelodysplastic syndrome.

    PubMed

    Kröger, Nicolaus

    2012-06-14

    Allogeneic hematopoietic stem cell transplantation (SCT) is well accepted as a curative treatment approach for younger patients with myelodysplastic syndrome (MDS) and has become one of the most frequent indications for allogeneic SCT as reported to the Center for International Blood and Marrow Transplant Research. However, MDS patients are usually elderly with a median age of approximately 75 years at diagnosis. Large register studies have confirmed the feasibility of the procedure in elderly MDS patients; and in the register of the European Group for Blood and Marrow Transplantation, one-third of the allogeneic transplant procedures for MDS were performed in 2010 in patients older than 60 years. Despite its curative potential, its role in the treatment of elderly MDS patients is less defined. Because of the inherent complications of the transplantation leading to treatment-related mortality and the risk of relapse, a careful calculation of the benefit for each patient is mandatory, taking into account comorbidities, disease status, donor selection, and effective nontransplant therapies. Prospective multicenter studies are needed to define optimal intensity of the conditioning regimen, timing of transplantation within a treatment algorithm, including drug-based therapies, and posttransplant strategies to reduce the risk of relapse.

  10. B-Cell-Based and Soluble Biomarkers in Body Liquids for Predicting Acute/Chronic Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation.

    PubMed

    Juric, Mateja Kralj; Shevtsov, Maxim; Mozes, Petra; Ogonek, Justyna; Crossland, Rachel E; Dickinson, Anne M; Greinix, Hildegard T; Holler, Ernst; Weissinger, Eva M; Multhoff, Gabriele

    2016-01-01

    Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the main curative therapy for hematological malignancy such as leukemias, lymphomas, or multiple myelomas and some other hematological disorders. In this therapy, cure of hematological diseases relies on graft-versus-malignancy effects by allogenic immune cells. However, severe posttransplant treatment-associated complications such as acute graft-versus-host disease (aGvHD) and chronic graft-versus-host disease (cGvHD) limit this approach. Most research into GvHD has concentrated on the aGvHD, while the more complex and multifaceted chronic form has been largely poorly investigated. cGvHD is a multi-organ autoimmune disorder and is the major cause of non-relapse morbidity and mortality following allo-HSCT, occurring in about 50% of patients, or 13,000-15,000 patients per year worldwide. Therefore, there is a high medical need for an early prediction of these therapy-associated toxicities. Biomarkers have gained importance over the last decade in diagnosis, in prognosis, and in prediction of pending diseases or side effects. Biomarkers can be cells, factors isolated from target tissues, or soluble factors that can be detected in body fluids. In this review, we aim to summarize some of the recent developments of biomarkers in the field of allo-HSCT. We will focus on cell-based biomarkers (B-cell subsets) for cGvHD and soluble factors including microRNA (miRNA), which are excreted into serum/plasma and urine. We also discuss the potential role of cytosolic and extracellular 70 kDa heat shock proteins (HSP70) as potential biomarkers for aGvHD and their role in preclinical models. Proteomic biomarkers in the blood have been used as predictors of treatment responses in patients with aGvHD for many years. More recently, miRNAs have been found to serve as a biomarker to diagnose aGvHD in the plasma. Another development relates to urine-based biomarkers that are usually detected by capillary electrophoresis

  11. B-Cell-Based and Soluble Biomarkers in Body Liquids for Predicting Acute/Chronic Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation

    PubMed Central

    Juric, Mateja Kralj; Shevtsov, Maxim; Mozes, Petra; Ogonek, Justyna; Crossland, Rachel E.; Dickinson, Anne M.; Greinix, Hildegard T.; Holler, Ernst; Weissinger, Eva M.; Multhoff, Gabriele

    2017-01-01

    Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the main curative therapy for hematological malignancy such as leukemias, lymphomas, or multiple myelomas and some other hematological disorders. In this therapy, cure of hematological diseases relies on graft-versus-malignancy effects by allogenic immune cells. However, severe posttransplant treatment-associated complications such as acute graft-versus-host disease (aGvHD) and chronic graft-versus-host disease (cGvHD) limit this approach. Most research into GvHD has concentrated on the aGvHD, while the more complex and multifaceted chronic form has been largely poorly investigated. cGvHD is a multi-organ autoimmune disorder and is the major cause of non-relapse morbidity and mortality following allo-HSCT, occurring in about 50% of patients, or 13,000–15,000 patients per year worldwide. Therefore, there is a high medical need for an early prediction of these therapy-associated toxicities. Biomarkers have gained importance over the last decade in diagnosis, in prognosis, and in prediction of pending diseases or side effects. Biomarkers can be cells, factors isolated from target tissues, or soluble factors that can be detected in body fluids. In this review, we aim to summarize some of the recent developments of biomarkers in the field of allo-HSCT. We will focus on cell-based biomarkers (B-cell subsets) for cGvHD and soluble factors including microRNA (miRNA), which are excreted into serum/plasma and urine. We also discuss the potential role of cytosolic and extracellular 70 kDa heat shock proteins (HSP70) as potential biomarkers for aGvHD and their role in preclinical models. Proteomic biomarkers in the blood have been used as predictors of treatment responses in patients with aGvHD for many years. More recently, miRNAs have been found to serve as a biomarker to diagnose aGvHD in the plasma. Another development relates to urine-based biomarkers that are usually detected by capillary

  12. Stem cell transplantation for ischemic stroke.

    PubMed

    Boncoraglio, Giorgio Battista; Bersano, Anna; Candelise, Livia; Reynolds, Brent A; Parati, Eugenio A

    2010-09-08

    Studies in animal models of ischemic stroke have shown that stem cells transplanted into the brain can lead to functional improvement. However, to date, evidence for the benefits of stem cell transplantation in ischemic stroke patients is lacking. To assess the efficacy and safety of stem cell transplantation compared with conventional treatments in patients with ischemic stroke. We searched the Cochrane Stroke Group Trials Register (last searched February 2010), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, Issue 3), MEDLINE (1966 to August 2008), EMBASE (1980 to August 2008), Science Citation Index (1900 to August 2008), and BIOSIS (1926 to August 2008). We handsearched potentially relevant conference proceedings, screened reference lists, and searched ongoing trials and research registers (last searched November 2008). We also contacted individuals active in the field and stem cell manufacturers (last contacted December 2008). We included randomized controlled trials (RCTs) recruiting patients with ischemic stroke, in any phase of the disease, and an ischemic lesion confirmed by computerized tomography or magnetic resonance imaging scan. We included all types of stem cell transplantation regardless of cell source (autograft, allograft, or xenograft; embryonic, fetal, or adult; from brain or other tissues), route of cell administration (systemic or local), and dosage. The primary outcome was efficacy (assessed as combined functional outcome or disability and dependency) at longer follow-up (minimum six months). Secondary outcomes included post-procedure safety outcomes (death, worsening of neurological deficit, infections and neoplastic transformation). Two review authors independently extracted data and assessed trial quality. We contacted study authors for additional information. We identified three very small RCTs. Two are still awaiting classification because only subgroups of patients could be included in this meta

  13. B Cell Immunity in Solid Organ Transplantation

    PubMed Central

    Karahan, Gonca E.; Claas, Frans H. J.; Heidt, Sebastiaan

    2017-01-01

    The contribution of B cells to alloimmune responses is gradually being understood in more detail. We now know that B cells can perpetuate alloimmune responses in multiple ways: (i) differentiation into antibody-producing plasma cells; (ii) sustaining long-term humoral immune memory; (iii) serving as antigen-presenting cells; (iv) organizing the formation of tertiary lymphoid organs; and (v) secreting pro- as well as anti-inflammatory cytokines. The cross-talk between B cells and T cells in the course of immune responses forms the basis of these diverse functions. In the setting of organ transplantation, focus has gradually shifted from T cells to B cells, with an increased notion that B cells are more than mere precursors of antibody-producing plasma cells. In this review, we discuss the various roles of B cells in the generation of alloimmune responses beyond antibody production, as well as possibilities to specifically interfere with B cell activation. PMID:28119695

  14. Management issues in hematopoietic stem cell transplantation.

    PubMed

    Rice, Robert David; Bailey, Gay

    2009-05-01

    To describe the leadership and management challenges of creating and maintaining a comprehensive hematopoietic stem cell transplant program. Research studies, review articles, databases, and web sites. Nurses at all levels of practice must conceptualize and execute expert specialized care through all phases of transplantation. Attention must be paid to specialized functions such as care coordination and case management, as well as scope of practice. Focus must be given to quality assessment and improvement. As the field of transplant grows and evolves, expert nursing leadership will be required to manage the continuum of care as patients move between health care settings. The increased emphasis on outpatient care, cost containment, and consumer and regulatory demand for quality will continue to challenge nurse leaders to manage creative enterprises.

  15. Hematopoietic cell transplantation: a curative option for sickle cell disease.

    PubMed

    Krishnamurti, Lakshmanan

    2007-12-01

    Sickle cell disease is associated with considerable morbidity and premature mortality. Hematopoietic cell transplantation offers the possibility of cure and is associated with excellent results in pediatric patients receiving stem cell transplantation from a matched sibling donor. Reduced intensity conditioning regimen have the potential to further reduce regimen related morbidity and mortality. Improved understanding of the natural history of complications such as stroke and pulmonary hypertension, effects of treatments, such as hydroxyurea and blood transfusions, as well as the impact of transplantation on organ damage are likely to influence the timing and indication of transplantation. Improvements in preparative regimen may enable the safe use of alternate source of stem cells such as unrelated matched donors and further improve the applicability and acceptability of this treatment.

  16. Myeloid derived suppressor cells in transplantation.

    PubMed

    Lees, Jason R; Azimzadeh, Agnes M; Bromberg, Jonathan S

    2011-10-01

    Myeloid derived suppressor cells (MDSC) are a heterogeneous population of hematopoietic derived cell precursors that can suppress immune responses in a variety of inflammatory settings. Here we review recent studies detailing expansion of phenotypically and functionally disparate MDSC. Findings related to MDSC accumulation, activation, and mechanisms utilized in immune suppression are presented. Further, we discuss recent reports that suggest MDSC are expanded during transplantation and that modulation of MDSC can participate in preventing graft rejection.

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

    PubMed

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

    2014-11-01

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

  18. Design of Injectable Materials to Improve Stem Cell Transplantation

    PubMed Central

    Marquardt, Laura M.

    2017-01-01

    Stem cell-based therapies are steadily gaining traction for regenerative medicine approaches to treating disease and injury throughout the body. While a significant body of work has shown success in preclinical studies, results often fail to translate in clinical settings. One potential cause is the massive transplanted cell death that occurs post injection, preventing functional integration with host tissue. Therefore, current research is focusing on developing injectable hydrogel materials to protect cells during delivery and to stimulate endogenous regeneration through interactions of transplanted cells and host tissue. This review explores the design of targeted injectable hydrogel systems for improving the therapeutic potential of stem cells across a variety of tissue engineering applications with a focus on hydrogel materials that have progressed to the stage of preclinical testing. PMID:28868235

  19. Hematopoietic stem cell transplantation for progressive multiple sclerosis: failure of a total body irradiation-based conditioning regimen to prevent disease progression in patients with high disability scores.

    PubMed

    Burt, Richard K; Cohen, Bruce A; Russell, Eric; Spero, Kenneth; Joshi, Akash; Oyama, Yu; Karpus, William J; Luo, Kehuan; Jovanovic, Borko; Traynor, Ann; Karlin, Karyn; Stefoski, Dusan; Burns, William H

    2003-10-01

    There were 21 patients with rapidly progressive multiple sclerosis (MS) treated on a phase 1/2 study of intense immune suppressive therapy and autologous hematopoietic stem cell (HSC) support with no 1-year mortality. Following transplantation, one patient had a confirmed acute attack of MS. Neurologic progression defined by the expanded disability status scale (EDSS) did not increase in disability by 1.0 or more steps in any of 9 patients with a pretransplantation EDSS of 6.0 or less. In 8 of 12 patients with high pretransplantation disability scores (EDSS > 6.0), progressive neurologic disability as defined by at least a 1-point increase in the EDSS has occurred and was manifested as gradual neurologic deterioration. There were 2 patients with a pretransplantation EDSS of 7.0 and 8.0 who died from complications of progressive disease at 13 and 18 months following treatment. Our experience suggests that intense immune suppression using a total body irradiation (TBI)-based regimen and hematopoietic stem cell transplantation (HSCT) are not effective for patients with progressive disease and high pretransplantation disability scores. Further studies are necessary to determine the role of intense immune suppressive therapy and HSC support in ambulatory patients with less accumulated disability and more inflammatory disease activity. Specifically, more patients and longer follow-up would be required in patients with an EDSS of 6.0 or less before drawing conclusions on this subgroup.

  20. Hematopoietic cell transplantation for aplastic anemia.

    PubMed

    Kumar, Rajat; Bonfim, Carmem; George, Biju

    2017-09-04

    Improvements in allogeneic hematopoietic cell transplantation (HCT) with better donor selection, conditioning regimens and graft vs. host disease prophylaxis make it reasonable to move HCT earlier in the algorithm for management of severe aplastic anemia (SAA). Recent progress in transplantation is reviewed whereas issues related to developing countries are also addressed. Multiple research centers are reporting on clonality, mutations and RK1 telomere disorders in SAA, which may help to choose the most appropriate therapy upfront. Eltrombopag, in combination with immunosuppressive therapy (IST), has shown remarkable improvement over historical IST, and long-term follow-up is awaited. In younger patients and in experienced centers, matched unrelated-donor (MUD) and related haploidentical transplants (haplo-HCT) are being reported with survival approaching that seen with sibling transplants. Literature from resource-limited countries highlight the need to modify guidelines to make them affordable and cost-effective. Bone marrow remains the graft source of choice; peripheral blood stem cells may be acceptable in special circumstances in resource-constrained countries. The potential of novel research findings and new therapeutic trials should be maximized by validation in different centers, countries and patient populations to provide personalized care to patients with aplastic anemia.

  1. Group-Based Trajectory Modeling of Distress and Well-Being Among Caregivers of Children Undergoing Hematopoetic Stem Cell Transplant.

    PubMed

    Sands, Stephen A; Mee, Laura; Bartell, Abraham; Manne, Sharon; Devine, Katie A; Savone, Mirko; Kashy, Deborah A

    2016-08-20

    OBJECTIVE : To examine the trajectories of caregiver psychological responses in the year following their child's hematopoetic stem cell transplant (HSCT), and whether cognitive and social processing strategies differentiated between trajectories.  METHOD : One hundred and eight caregivers randomized to the control condition of a cognitive-behavioral intervention study completed measures of distress, coping, and social support at baseline, 1 month, 6 months, and 1 year post HSCT of their child.  RESULTS : The majority reported moderate or low anxiety, depression, or distress that decreased over time, but a small group demonstrated high anxiety, depression, or distress that persisted or increased over time. Maladaptive coping was highest among caregivers in the high-persistent distress subgroup compared with the moderate-decreasing and low-stable groups. Adaptive coping was minimally associated with trajectory subgroups.  CONCLUSIONS : Screening HSCT caregivers for distress and maladaptive coping may be useful in identifying caregivers likely to experience persistently high distress who may benefit from psychological intervention.

  2. Outcomes of lung transplantation after allogeneic hematopoietic stem cell transplantation.

    PubMed

    Cheng, Guang-Shing; Edelman, Jeffrey D; Madtes, David K; Martin, Paul J; Flowers, Mary E D

    2014-08-01

    Other than lung transplantation (LT), no specific therapies exist for end-stage lung disease resulting from hematopoietic stem cell transplantation (HCT)-related complications, such as bronchiolitis obliterans syndrome (BOS). We report the indications and outcomes in patients who underwent LT after HCT for hematologic disease from a retrospective case series at our institution and a review of the medical literature. We identified a total of 70 cases of LT after HCT, including 9 allogeneic HCT recipients from our institution who underwent LT between 1990 and 2010. In our cohort, the median age was 16 years (range, 10 to 35 years) at the time of HCT and 34 years (range, 17 to 44 years) at the time of LT, with a median interval between HCT and LT of 10 years (range, 2.9 to 27 years). Indications for LT-included pulmonary fibrosis (n = 4), BOS (n = 3), interstitial pneumonitis related to graft-versus-host disease (GVHD) (n = 1), and primary pulmonary hypertension (n = 1). Median survival was 49 months (range, 2 weeks to 87 months), and 1 patient remains alive at more than 3 years after LT. Survival at 1 year and 5 years after LT was 89% and 37%, respectively. In the medical literature between 1992 and July 2013, we identified 20 articles describing 61 cases of LT after HCT from various centers in the United States, Europe, and Asia. Twenty-six of the 61 cases (43%) involved patients age <18 years at the time of LT. BOS and GVHD of the lung were cited as the indication for LT in the majority of cases (80%; n = 49), followed by pulmonary fibrosis and interstitial lung disease (20%; n = 12). In publications reporting 3 or more cases with a follow-up interval ranging from the immediate postoperative period to 16 years, the survival rate was 71% (39 of 55). Most deaths were attributed to long-term complications of the lung allograft, including infections and BOS. Two deaths were related to recurrent or relapsed hematologic malignancy. LT can prolong survival in some

  3. iPS cell transplantation for traumatic spinal cord injury

    PubMed Central

    Goulão, Miguel; Lepore, Angelo C.

    2016-01-01

    A large body of work has been published on transplantation of a wide range of neural stem and progenitor cell types derived from the developing and adult CNS, as well as from pluripotent embryonic stem cells, in models of traumatic spinal cord injury (SCI). However, many of these cell-based approaches present practical issues for clinical translation such as ethical cell derivation, generation of potentially large numbers of homogenously prepared cells, and immune rejection. With the advent of induced Pluripotent Stem (iPS) cell technology, many of these issues may potentially be overcome. To date, a number of studies have demonstrated integration, differentiation into mature CNS lineages, migration and long-term safety of iPS cell transplants in a variety of SCI models, as well as therapeutic benefits in some cases. Given the clinical potential of this advance in stem cell biology, we present a concise review of studies published to date involving iPS cell transplantation in animal models of SCI. PMID:26201863

  4. Systemically transplanted human gingiva-derived mesenchymal stem cells contributing to bone tissue regeneration.

    PubMed

    Xu, Quan-Chen; Wang, Zhi-Guo; Ji, Qiu-Xia; Yu, Xin-Bo; Xu, Xiao-Yan; Yuan, Chang-Qing; Deng, Jing; Yang, Pi-Shan

    2014-01-01

    As novel postnatal stem cells, gingiva-derived mesenchymal stem cells (GMSCs) have been considered as an ideal candidate cell resource for tissue engineering and cell-based therapies. GMSCs implanted into sites of injury have been confirmed to promote the injury repair. However, no studies have demonstrated whether systemically transplanted GMSCs can home to the bone injuries and contribute to the new bone formation in vivo. In this study, we transplanted human GMSCs into C57BL/6J mice with defects in mandibular bone via the tail vein to explore the capacity of transplanted GMSCs to promote bone regeneration. Results showed that the transplanted GMSCs were detected in the bone defects and employed in new bone formation. And the newly formed bone area in mice with GMSCs transplantation was significantly higher than that in control mice. Our findings indicate that systemically transplanted GMSCs can not only home to the mandibular defect but also promote bone regeneration.

  5. Antibacterial Resistance in Patients with Hematopoietic Stem Cell Transplantation

    PubMed Central

    Alp, Sehnaz; Akova, Murat

    2017-01-01

    Recipients of hematopoietic stem cell transplantation (HSCT) are at substantial risk of bacterial, fungal, viral, and parasitic infections depending on the time elapsed since transplantation, presence of graft-versus-host disease (GVHD), and the degree of immunosuppression. Infectious complications in HSCT recipients are associated with high morbidity and mortality. Bacterial infections constitute the major cause of infectious complications, especially in the early post-transplant period. The emergence of antibacterial resistance complicates the management of bacterial infections in this patient group. Multidrug-resistant bacterial infections in this group of patients have attracted considerable interest and may lead to significant morbidity and mortality. Empirical antibacterial therapy in patients with HSCT and febrile neutropenia has a critical role for survival and should be based on local epidemiology. This review attempts to provide an overview of risk factors and epidemiology of emerging resistant bacterial infections and their management in HSCT recipients. PMID:28101308

  6. Haploidentical Hematopoietic Stem Cell Transplantation as Platform for Post-transplant Cellular Therapy

    PubMed Central

    Kongtim, Piyanuch; Lee, Dean A.; Cooper, Laurence J. N.; Kebriaei, Partow; Champlin, Richard E.; Ciurea, Stefan O.

    2016-01-01

    Haploidentical transplantation can extend the opportunity for transplantation to almost all patients who lack an HLA-matched donor. Advances in the field of haploidentical transplantation have led to a marked decrease in treatment-related mortality, allowing investigators to focus on developing rationale pre- and peri-remission therapies aimed at preventing disease relapse post-transplant. Due to widespread availability, low treatment-related mortality and cost, haploidentical donors may become the preferred “alternative” donors for allogeneic hematopoietic stem cell transplantation. One of the major advantages of using a related donor is the possibility to collect or generate additional cellular products from the same immediate available donor, which will not be rejected. Infusion of these cells in the peri-transplant period, derived from the same immune system, is opening the possibility to markedly enhance the anti-tumor effects of the graft and hasten immunologic reconstitution post-transplant. PMID:26172479

  7. Sinonasal disorders in hematopoietic stem cell transplantation.

    PubMed

    Bento, Lucas Ricci; Ortiz, Erica; Nicola, Ester Maria Danieli; Vigorito, Afonso C; Sakano, Eulalia

    2014-01-01

    hematopoietic stem cell transplantation (HSCT) is associated with more respiratory infections due to immunosuppression. this study aimed to verify the frequency of rhinosinusitis after HSCT, and the association between rhinosinusitis and chronic graft vs. host disease (GVHD) and type of transplantation, clinical treatment, surgical treatment, and survival. this was a retrospective study in a tertiary university hospital. A total of 95 patients with hematological diseases undergoing HSCT between 1996 and 2011 were selected. chronic myeloid leukemia was the most prevalent disease. The type of transplant most often performed was the allogenic type (85.26%). The frequency of rhinosinusitis was 36%, with no difference between the autologous and the allogenic types. Chronic GVHD occurred in 30% of patients. Patients with GVHD had a higher frequency and recurrence of rhinosinusitis, in addition to more frequent need for endoscopic sinusectomy and decreased overall survival. there was a higher frequency of rhinosinusitis in HSCT and GVHD. The type of transplant does not appear to predispose to the occurrence of rhinosinusitis. GVHD seems to be an aggravating factor and requires a more stringent treatment. Copyright © 2014 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  8. T-cell post-transplantation lymphoproliferative disorders after cardiac transplantation: a single institutional experience.

    PubMed

    Draoua, H Y; Tsao, Lawrence; Mancini, Donna M; Addonizio, Linda J; Bhagat, Govind; Alobeid, Bachir

    2004-11-01

    Post-transplantation lymphoproliferative disorders (PTLDs) are a well-recognized and potentially life-threatening complication of solid organ transplantation. While the vast majority of PTLDs are B-cell lymphoproliferations, T-cell PTLDs are rarely seen. Among 898 patients receiving cardiac transplants between 1990 and 2003, 34 patients (3.8%) developed PTLDs with two (0.2%) T-cell PTLDs, 31 (3.5%) B-cell PTLDs and one (0.1%) natural killer cell PTLD. An additional three cases of T-cell PTLD were identified among all cardiac transplant patients followed at our institution. These T-cell PTLDs comprised a heterogeneous group of Epstein-Barr virus negative lymphoproliferations that developed late after transplantation and followed an aggressive course.

  9. Intranigral transplantation of epigenetically induced BDNF-secreting human mesenchymal stem cells: implications for cell-based therapies in Parkinson's disease.

    PubMed

    Somoza, Rodrigo; Juri, Carlos; Baes, Mauricio; Wyneken, Ursula; Rubio, Francisco Javier

    2010-11-01

    It is thought that the ability of human mesenchymal stem cells (hMSC) to deliver neurotrophic factors might be potentially useful for the treatment of neurodegenerative disorders. The aim of the present study was to characterize signals and/or molecules that regulate brain-derived neurotrophic factor (BDNF) protein expression/delivery in hMSC cultures and evaluate the effect of epigenetically generated BDNF-secreting hMSC on the intact and lesioned substantia nigra (SN). We tested 4 different culture media and found that the presence of fetal bovine serum (FBS) decreased the expression of BDNF, whereas exogenous addition of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) to serum-free medium was required to induce BDNF release (125 ± 12 pg/day/10⁶ cells). These cells were called hM(N)SC. Although the induction medium inhibited the expression of alpha smooth muscle actin (ASMA), an hMSC marker, and increased the nestin-positive subpopulation of hMSC cultures, the ability to express BDNF was restricted to the nestin-negative subpopulation. One week after transplantation into the SN, the human cells integrated into the surrounding tissue, and some showed a dopaminergic phenotype. We also observed the activation of Trk receptors for neurotrophic factors around the implant site, including the BDNF receptor TrkB. When we transplanted these cells into the unilateral lesioned SN induced by striatal injection of 6-hydroxydopamine (6-OHDA), a significant hypertrophy of nigral tyrosine hydroxylase (TH)(+) cells, an increase of striatal TH-staining and stabilization of amphetamine-induced motor symptoms were observed. Therefore, hMSC cultures exposed to the described induction medium might be highly useful as a vehicle for neurotrophic delivery to the brain and specifically are strong candidates for future therapeutic application in Parkinson's disease.

  10. Clinical Allogeneic and Autologous Islet Cell Transplantation: Update

    PubMed Central

    2011-01-01

    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. PMID:21785738

  11. [Research progress of cells and cell-transplantation methods for periodontal tissue engineering].

    PubMed

    Li, Wei; Meng, Xuemei

    2010-10-01

    To introduce the cells and cell-transplantation methods for periodontal tissue engineering. Recent literature about application of cell-based therapy in periodontal tissue engineering was extensively reviewed, the cells and cell-transplantation methods were investigated. Mesenchymal stem cells were important cell resources for periodontal tissue engineering, among which periodontal ligament stem cells were preferred. Bone marrow mesenchymal stem cells had several disadvantages in clinical application, and adipose-derived stem cells might be a promising alternative; different transplantation methods could all promote periodontal regeneration to some extent. Single-cell suspension injection could only promote a little gingival regeneration, and tissue engineered scaffolds still needed some improvement to be used in periodontal regeneration, while cell sheet technique, with great cell loading ability and no need of scaffolds, could promote regeneration of cementum, periodontal ligament, and alveolar bone under different conditions. Multipotent stem cells are fit to be used in periodontal tissue engineering; improvement of cell-transplantation methods will further promote periodontal regeneration.

  12. Autologous and allogeneic hematopoietic stem cell transplantation in follicular lymphoma.

    PubMed

    Bhatt, V R; Armitage, J O

    2016-01-01

    High-dose chemotherapy and autologous stem cell transplantation (ASCT) improve survival in follicular lymphoma; however, relapse remains the most common cause of death. The lower risk of relapse with allogeneic SCT (alloSCT) is offset by a high transplant-related mortality (TRM). English articles indexed in the MEDLINE database were reviewed to discuss the role of graft purging, rituximab maintenance after ASCT, reduced-intensity conditioning (RIC) alloSCT, T-cell depletion, donor lymphocyte infusion (DLI) and alternate donor sources. Optimal salvage consolidation strategy may utilize ASCT following non-total body irradiation-based conditioning regimen in second remission. Rituximab maintenance after ASCT may improve molecular remission but is not yet shown to improve overall survival. RIC alloSCT permits its use in older and less-fit patients. Studies with T-cell depleted graft failed to reduce TRM despite a decline in graft-versus-host disease; however, these studies did demonstrate a therapeutic role of DLI in post-transplant relapses. In recent years, haploidentical and umbilical cord blood donors have emerged as alternative donor sources, with outcomes comparable to matched unrelated donor SCT. In the future, incorporation of novel therapeutic agents, improved risk-adapted treatment strategies, and advancement of transplant techniques may provide a better chance of survival.

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

    PubMed

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

    2013-01-01

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

  14. Cryptococcal meningitis post autologous stem cell transplantation.

    PubMed

    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.

  15. Arrhythmias in the setting of hematopoietic cell transplants.

    PubMed

    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=<0.001), a greater probability of an intensive care unit admission (52% vs 7%; P<0.001), greater probability of in-hospital deaths (28% vs 3%, P<0.001), and greater probability of death within 1 year of transplant (41% vs 15%; P<0.001) compared with patients without arrhythmia at any time. In a multivariate model including age at transplant, 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; P<0.001). Our data suggest that arrhythmias after transplants are associated with significant morbidity and mortality. A prospective study of arrhythmia in the transplant setting is warranted.

  16. Hematopoietic stem cell transplantation for people with sickle cell disease.

    PubMed

    Oringanje, Chioma; Nemecek, Eneida; Oniyangi, Oluseyi

    2016-05-19

    Sickle cell disease is a genetic disorder involving a defect in the red blood cells due to its sickled hemoglobin. The main therapeutic interventions include preventive and supportive measures. Hematopoietic stem cell transplantations are carried out with the aim of replacing the defective cells and their progenitors (hematopoietic (i.e. blood forming) stem cells) in order to correct the disorder. This is an update of a previously published review. To determine whether stem cell transplantation can improve survival and prevent symptoms and complications associated with sickle cell disease. To examine the risks of stem cell transplantation against the potential long-term gain for people with sickle cell disease. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Group's Haemoglobinopathies Trials Register complied from electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (updated each new issue of The Cochrane Library) and quarterly searches of MEDLINE.Unpublished work was identified by searching the abstract books of major conference proceedings and we conducted a search of the website: www.ClinicalTrials.gov.Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 06 October 2015. Randomized controlled and quasi-randomized studies that compared any method of stem cell transplantation with either each other or with any of the preventive or supportive interventions (e.g. periodic blood transfusion, use of hydroxyurea, antibiotics, pain relievers, supplemental oxygen) in people with sickle cell disease irrespective of the type of sickle cell disease, gender and setting. No relevant trials were identified. Ten trials were identified by the initial search and none for the update. None of these trials were suitable for inclusion in this review. Reports on the use of hematopoietic stem cell transplantation improving survival and preventing symptoms and complications associated with sickle cell

  17. Mesenchymal stem cell transplantation in multiple sclerosis.

    PubMed

    Cohen, Jeffrey A

    2013-10-15

    Mesenchymal stem cells (MSCs) are pluripotent non-hematopoietic precursor cells that can be isolated from bone marrow and numerous other tissues, culture-expanded to purity, and induced to differentiate in vitro and in vivo into mesodermal derivatives. MSCs exhibit many phenotypic and functional similarities to pericytes. The immunomodulatory, tissue protective, and repair-promoting properties of MSCs demonstrated both in vitro and in animal models make them an attractive potential therapy for MS and other conditions characterized by inflammation and/or tissue injury. Other potential advantages of MSCs as a therapeutic include the relative ease of culture expansion, relative immunoprivilege allowing allogeneic transplantation, and their ability to traffic from blood to areas of tissue allowing intravascular administration. The overall published experience with MSC transplantation in MS is modest, but several small case series and preliminary studies yielded promising results. Several groups, including us, recently initiated formal studies of autologous, culture-expanded, bone marrow-derived MSC transplantation in MS. Although there are several potential safety concerns, to date, the procedure has been well tolerated. Future studies that more definitively assess efficacy also will need to address several technical issues. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Stem cell transplantation for rheumatic autoimmune diseases

    PubMed Central

    Hügle, Thomas; van Laar, Jacob M

    2008-01-01

    Immunoablative therapy and hematopoietic stem cell transplantation (HSCT) is an intensive treatment modality aimed at 'resetting' the dysregulated immune system of a patient with immunoablative therapy and allow outgrowth of a nonautogressive immune system from reinfused hematopoietic stem cells, either from the patient (autologous HSCT) or a healthy donor (allogeneic HSCT). HSCT has been shown to induce profound alterations of the immune system affecting B and T cells, monocytes, and natural killer and dendritic cells, resulting in elimination of autoantibody-producing plasma cells and in induction of regulatory T cells. Most of the available data have been collected through retrospective cohort analyses of autologous HSCT, case series, and translational studies in patients with refractory autoimmune diseases. Long-term and marked improvements of disease activity have been observed, notably in systemic sclerosis, systemic lupus erythematosus, and juvenile idiopathic arthritis, and treatment-related morbidity and mortality have improved due to better patient selection and modifications of transplant regimens. Treatment-related mortality has decreased to approximately 7%. Prospective, randomised, controlled clinical trials are ongoing or planned in systemic sclerosis, systemic lupus erythematosus, and several nonrheumatological conditions. PMID:18947373

  19. Risk of diffuse large B-cell lymphoma after solid organ transplantation in the United States

    PubMed Central

    Gibson, Todd M.; Engels, Eric A.; Clarke, Christina A.; Lynch, Charles F.; Weisenburger, Dennis D.; Morton, Lindsay M.

    2014-01-01

    Non-Hodgkin lymphoma (NHL) arising in the context of immunosuppression is an important adverse outcome following solid organ transplantation. Diffuse large B-cell lymphoma (DLBCL) is the most commonly diagnosed subtype of post-transplant NHL, but few studies of transplant recipients have examined subtype-specific risks. Therefore, we examined DLBCL risk in the Transplant Cancer Match Study, including registry-based cancer ascertainment among 96,615 solid organ transplants performed from 2000–2008. We determined standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) comparing DLBCL risk in transplant recipients to that in the general population, and used multivariable Poisson regression models to assess the impact of potential risk factors. We identified 321 incident cases of DLBCL, over 12 times more than expected based on general population rates (SIR=12.6, 95% CI=11.2–14.0). SIRs were highest in young recipients and those receiving a lung or pancreas/kidney-pancreas transplant, and were greatly elevated for extranodal DLBCLs at the site of the transplant compared to other sites. DLBCL risk was highest in the first year following transplant, and SIRs for early-onset DLBCL risk were elevated in association with EBV negative serostatus and use of polyclonal antibody induction therapy. In conclusion, associations between recipient and transplant factors and post-transplant DLBCL risk suggest a complicated interrelationship among multiple risk factors and timing of disease. PMID:24753070

  20. CMV in Hematopoietic Stem Cell Transplantation

    PubMed Central

    de la Cámara, Rafael

    2016-01-01

    Due to its negative impact on the outcome of stem cell transplant (SCT) and solid organ transplant patients (SOT) CMV has been called “the troll of transplantation”. One of the greatest advances in the management of SCT has been the introduction of the preemptive strategy. Since its introduction, the incidence of the viremia, as expected, remains unchanged but there has been a marked decline in the incidence of early CMV disease. However, in spite of the advances in prevention of CMV disease, CMV is still today an important cause of morbidity and mortality. Late CMV disease is still occurring in a significant proportion of patients and the so-called indirect effects of CMV are causing significant morbidity and mortality. Fortunately there have been several advances in the development of new antivirals, adoptive immunotherapy and DNA-CMV vaccines that might transform the management of CMV in the near future. PMID:27413524

  1. Autologous stem cell transplant with gene therapy for Friedreich ataxia.

    PubMed

    Tajiri, Naoki; Staples, Meaghan; Kaneko, Yuji; Kim, Seung U; Zesiewicz, Theresa A; Borlongan, Cesar V

    2014-09-01

    We advance the overarching hypothesis that stem cell therapy is a potent treatment for Friedreich's ataxia (FRDA). Here, we discuss the feasibility of autologous transplantation in FRDA, highlighting the need for the successful isolation of the FRDA patient's bone marrow-derived mesenchymal stem cells, followed by characterization that these cells maintain the GAA repeat expansion and the reduced FXN mRNA expression, both hallmark features of FRDA. Next, we discuss the need for assessment of the proliferative capability and pluripotency of FRDA patient's bone marrow-derived mesenchymal stem cells. In particular, we view the need for characterizing the in vitro differentiation of bone marrow-derived mesenchymal stem cells into the two cell types primarily affected in FRDA, peripheral neurons and cardiomyocytes. Finally, we discuss the need to test the application of bone marrow-derived mesenchymal stem cells as potent autologous donor cells for FRDA. The demonstration of the functional correction of the mutated gene in these cells will be a critical endpoint of determining the potential of stem cell therapy in FRDA. We envision a gene-based cell transplant strategy as a likely therapeutic approach for FRDA, involving stable insertion of functional human bacterial artificial chromosomes or BACs containing the intact FXN gene into stem cells, thereafter leading to the expression of frataxin protein in differentiated neurons/cardiomyocytes. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Transplantation of choroid plexus epithelial cells into contusion-injured spinal cord of rats

    PubMed Central

    Kanekiyo, Kenji; Nakano, Norihiko; Noda, Toru; Yamada, Yoshihiro; Suzuki, Yoshihisa; Ohta, Masayoshi; Yokota, Atsushi; Fukushima, Masanori; Ide, Chizuka

    2016-01-01

    Purpose: The effect of the transplantation of choroid plexus epithelial cells (CPECs) on locomotor improvement and tissue repair including axonal extension in spinal cord lesions was examined in rats with spinal cord injury (SCI). Methods: CPECs were cultured from the choroid plexus of green fluorescent protein (GFP)-transgenic rats, and transplanted directly into the contusion-injured spinal cord lesions of rats of the same strain. Locomotor behaviors were evaluated based on BBB scores every week after transplantation until 4 weeks after transplantation. Histological and immunohistochemical examinations were performed at 2 days, and every week until 5 weeks after transplantation. Results: Locomotor behaviors evaluated by the BBB score were significantly improved in cell-transplanted rats. Numerous axons grew, with occasional interactions with CPECs, through the astrocyte-devoid areas. These axons exhibited structural characteristics of peripheral nerves. GAP-43-positive axons were found at the border of the lesion 2 days after transplantation. Cavity formation was more reduced in cell-transplanted than control spinal cords. CPECs were found within the spinal cord lesion, and sometimes in association with astrocytes at the border of the lesion until 2 weeks after transplantation. Conclusion: The transplantation of CPECs enhanced locomotor improvement and tissue recovery, including axonal regeneration, in rats with SCI. PMID:26923614

  3. Megakaryocytopoiesis in Stem Cell Transplantation

    DTIC Science & Technology

    1997-10-01

    test this hypothesis, nonadherent mononuclear PIXY321 promotes more rapid platelet recovery in rhesus cells (MNCs) from apheresis specimens of patients...with growth factors usually results in delayed platelet engraftment as compared to neutrophil recovery (1-4), requiring patients to be submitted to...repeated platelet transfusions. The overall objective of this research proposal is to investigate several laboratory protocols to improve megakaryocyte

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

    PubMed Central

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

    2015-01-01

    Adult patients with acute leukemia in need of a transplant but without a genoidentical donor are usually considered upfront for transplantation with stem cells from any other allogeneic source, rather than autologous stem cell transplantation. We used data from the European Society for Blood and Marrow Transplantation and performed a matched pair analysis on 188 T-cell-replete haploidentical and 356 autologous transplants done from January 2007 to December 2012, using age, diagnosis, disease status, cytogenetics, and interval from diagnosis to transplant as matching factors. “Haploidentical expert” centers were defined as having reported more than five haploidentical transplants for acute leukemia (median value for the study period). The median follow-up was 28 months. Multivariate analyses, including type of transplant categorized into three classes (“haploidentical regular”, “haploidentical expert” and autologous), conditioning intensity (reduced intensity versus myeloablative conditioning) and the random effect taking into account associations related to matching, showed that non-relapse mortality was higher following haploidentical transplants in expert (HR: 4.7; P=0.00004) and regular (HR: 8.98; P<10−5) centers. Relapse incidence for haploidentical transplants was lower in expert centers (HR:0.39; P=0.0003) but in regular centers was similar to that for autologous transplants. Leukemia-free survival and overall survival rates were higher following autologous transplantation than haploidentical transplants in regular centers (HR: 1.63; P=0.008 and HR: 2.31; P=0.0002 respectively) but similar to those following haploidentical transplants in expert centers. We conclude that autologous stem cell transplantation should presently be considered as a possible alternative to haploidentical transplantation in regular centers that have not developed a specific expert program. PMID:25637051

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

    PubMed

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

    2015-04-01

    Adult patients with acute leukemia in need of a transplant but without a genoidentical donor are usually considered upfront for transplantation with stem cells from any other allogeneic source, rather than autologous stem cell transplantation. We used data from the European Society for Blood and Marrow Transplantation and performed a matched pair analysis on 188 T-cell-replete haploidentical and 356 autologous transplants done from January 2007 to December 2012, using age, diagnosis, disease status, cytogenetics, and interval from diagnosis to transplant as matching factors. "Haploidentical expert" centers were defined as having reported more than five haploidentical transplants for acute leukemia (median value for the study period). The median follow-up was 28 months. Multivariate analyses, including type of transplant categorized into three classes ("haploidentical regular", "haploidentical expert" and autologous), conditioning intensity (reduced intensity versus myeloablative conditioning) and the random effect taking into account associations related to matching, showed that non-relapse mortality was higher following haploidentical transplants in expert (HR: 4.7; P=0.00004) and regular (HR: 8.98; P<10(-5)) centers. Relapse incidence for haploidentical transplants was lower in expert centers (HR:0.39; P=0.0003) but in regular centers was similar to that for autologous transplants. Leukemia-free survival and overall survival rates were higher following autologous transplantation than haploidentical transplants in regular centers (HR: 1.63; P=0.008 and HR: 2.31; P=0.0002 respectively) but similar to those following haploidentical transplants in expert centers. We conclude that autologous stem cell transplantation should presently be considered as a possible alternative to haploidentical transplantation in regular centers that have not developed a specific expert program.

  6. Navigating T Cell Immunometabolism in Transplantation.

    PubMed

    Tanimine, Naoki; Turka, Laurence A; Priyadharshini, Bhavana

    2017-09-19

    Recently, a new discipline termed "immunometabolism" has transformed the field of immunology. It encompasses the study of the intrinsic metabolic pathways of different immune subsets and their impact on cellular fate and function. For instance, broadly speaking, pro-inflammatory cells depend upon glycolysis and glutamine oxidation while cells involved in anti-inflammatory response such as Foxp3+ regulatory T cells (Tregs) utilize predominantly fatty acid oxidation. However, while a useful paradigm, this actually is a reductionist view and the engagement of these metabolic pathways is not mutually exclusive between these subsets. Over the past several years, new insights and new methods to better dissect, define, and harness the metabolic properties of immune cells for immunotherapeutic purposes have come to the forefront. In this review, we will discuss the metabolic heterogeneity of different T cells subsets as well as basic principles of integrative technologies, such as metabolomics, that can be used to better understand the metabolic signatures of immune responses. Given the interest of exploiting this information in the context of transplantation, we will highlight the scope of immunometabolism in unraveling novel mechanisms of immune regulation that can be manipulated to promote Treg stability and function while inhibiting T effectors to establish long-term transplantation tolerance.

  7. Ectonucleotidases in solid organ and allogeneic hematopoietic cell transplantation.

    PubMed

    Chernogorova, Petya; Zeiser, Robert

    2012-01-01

    Extracellular nucleotides are ubiquitous signalling molecules which modulate distinct physiological and pathological processes. Nucleotide concentrations in the extracellular space are strictly regulated by cell surface enzymes, called ectonucleotidases, which hydrolyze nucleotides to the respective nucleosides. Recent studies suggest that ectonucleotidases play a significant role in inflammation by adjusting the balance between ATP, a widely distributed proinflammatory danger signal, and the anti-inflammatory mediator adenosine. There is increasing evidence for a central role of adenosine in alloantigen-mediated diseases such as solid organ graft rejection and acute graft-versus-host disease (GvHD). Solid organ and hematopoietic cell transplantation are established treatment modalities for a broad spectrum of benign and malignant diseases. Immunological complications based on the recognition of nonself-antigens between donor and recipient like transplant rejection and GvHD are still major challenges which limit the long-term success of transplantation. Studies in the past two decades indicate that purinergic signalling influences the severity of alloimmune responses. This paper focuses on the impact of ectonucleotidases, in particular, NTPDase1/CD39 and ecto-5'-nucleotidase/CD73, on allograft rejection, acute GvHD, and graft-versus-leukemia effect, and on possible clinical implications for the modulation of purinergic signalling after transplantation.

  8. Ectonucleotidases in Solid Organ and Allogeneic Hematopoietic Cell Transplantation

    PubMed Central

    Chernogorova, Petya; Zeiser, Robert

    2012-01-01

    Extracellular nucleotides are ubiquitous signalling molecules which modulate distinct physiological and pathological processes. Nucleotide concentrations in the extracellular space are strictly regulated by cell surface enzymes, called ectonucleotidases, which hydrolyze nucleotides to the respective nucleosides. Recent studies suggest that ectonucleotidases play a significant role in inflammation by adjusting the balance between ATP, a widely distributed proinflammatory danger signal, and the anti-inflammatory mediator adenosine. There is increasing evidence for a central role of adenosine in alloantigen-mediated diseases such as solid organ graft rejection and acute graft-versus-host disease (GvHD). Solid organ and hematopoietic cell transplantation are established treatment modalities for a broad spectrum of benign and malignant diseases. Immunological complications based on the recognition of nonself-antigens between donor and recipient like transplant rejection and GvHD are still major challenges which limit the long-term success of transplantation. Studies in the past two decades indicate that purinergic signalling influences the severity of alloimmune responses. This paper focuses on the impact of ectonucleotidases, in particular, NTPDase1/CD39 and ecto-5′-nucleotidase/CD73, on allograft rejection, acute GvHD, and graft-versus-leukemia effect, and on possible clinical implications for the modulation of purinergic signalling after transplantation. PMID:23125523

  9. The Impact of Geographic Proximity to Transplant Center on Outcomes after Allogeneic Hematopoietic Stem Cell Transplantation

    PubMed Central

    Abou-Nassar, Karim E.; Kim, Haesook T.; Blossom, Jeff; Ho, Vincent T.; Soiffer, Robert J.; Cutler, Corey S.; Alyea, Edwin P.; Koreth, John; Antin, Joseph H.; Armand, Philippe

    2011-01-01

    BACKGROUND Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) need access to specialized care. We hypothesized that access to the transplant center after HSCT may be challenging for patients living in geographically distant areas, and that this would have an adverse effect on their outcome. METHODS We analyzed 1912 adult patients who underwent allogeneic HSCT at DF/BWCC between 1996 and 2009 and who resided within 6 hours driving time of the institution. Driving time from primary residence to DF/BWCC based on zipcode was determined using geographic information systems. RESULTS The median driving time (range) to DF/BWCC was 72 (2-358) minutes. When patients were stratified by driving time quartile, overall survival (OS) after HSCT was similar in the first year but worse after 1 year in patients in the top quartile (≥160 minutes driving time). In a landmark analysis of the 909 patients alive and free of disease at 1 year, 5-yr OS was 76% and 65% for patients in the 1st (≤40 minutes) and 4th (≥160 minutes) quartiles, respectively (p=0.027). This was confirmed in a multivariable analysis. The difference appeared to be mostly due to an increase in non-relapse mortality. The number of visits to the transplant center between day 100 and 365 after HSCT declined significantly with increasing driving time to the transplant center, which was independently associated with worse survival. CONCLUSION Long driving time to the transplant center is associated with worse OS in patients alive and disease-free one year after HSCT, independently of other patient-, disease- and HSCT related variables. This may be in part related to the lower frequency of post-HSCT visits in patients living farther away. PMID:21906576

  10. Hematopoietic stem cell transplantation in thalassemia major and sickle cell disease: indications and management recommendations from an international expert panel.

    PubMed

    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

    2014-05-01

    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.

  11. Hematopoietic stem cell transplantation in thalassemia major and sickle cell disease: indications and management recommendations from an international expert panel

    PubMed Central

    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

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

    PubMed

    Strober, Samuel

    2016-03-24

    The goals of tolerance in patients with solid organ transplants are to eliminate the lifelong need for immunosuppressive (IS) drugs and to prevent graft loss due to rejection or drug toxicity. Tolerance with complete withdrawal of IS drugs has been achieved in recipients of HLA-matched and mismatched living donor kidney transplants in 3 medical centers using hematopoietic cell transplants to establish mixed or complete chimerism. © 2016 by The American Society of Hematology.

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

    PubMed Central

    2016-01-01

    The goals of tolerance in patients with solid organ transplants are to eliminate the lifelong need for immunosuppressive (IS) drugs and to prevent graft loss due to rejection or drug toxicity. Tolerance with complete withdrawal of IS drugs has been achieved in recipients of HLA-matched and mismatched living donor kidney transplants in 3 medical centers using hematopoietic cell transplants to establish mixed or complete chimerism. PMID:26796362

  14. Major complications following hematopoietic stem cell transplantation.

    PubMed

    Afessa, Bekele; Peters, Steve G

    2006-06-01

    Tens of thousands of patients undergo hematopoietic stem cell transplantation (HSCT) annually, 15 to 40% of whom are admitted to the intensive care unit. Pulmonary complications are the most life threatening conditions that develop in HSCT recipients. Both infectious and noninfectious complications occur more frequently in allogeneic HSCT. The management of HSCT recipients requires knowledge of their immune status, appropriate diagnostic evaluation, and early treatment. During the pre-engraftment phase (0 to 30 days after transplant), the most prevalent pathogens causing infection are bacteria and Candida species and, if the neutropenia persists, Aspergillus species. The early post-engraftment phase (30 to 100 days) is characterized by cytomegalovirus (CMV), Pneumocystis jiroveci, and Aspergillus infections. During the late posttransplant phase (> 100 days), allogeneic HSCT recipients are at risk for CMV, community-acquired respiratory virus, and encapsulated bacterial infections. Antigen and polymerase chain reaction assays are important for the diagnosis of CMV and Aspergillus infections. Diffuse alveolar hemorrhage (DAH) and peri-engraftment respiratory distress syndrome occur in both allogeneic and autologous HSCT recipients, usually during the first 30 days. Bronchiolitis obliterans occurs exclusively in allogeneic HSCT recipients with graft versus host disease. Idiopathic pneumonia syndrome occurs at any time following transplant. Bronchoscopy is usually helpful for the diagnosis of the infectious pulmonary complications and DAH.

  15. Immunogenomics of hematopoietic stem cell transplantation.

    PubMed

    Charron, Dominique

    2005-04-01

    Recipients of allogeneic hematopoietic stem cell transplantation (HSCT) incur the risk of graft-versus-host disease even when the donor is a sibling who shares the Major Histocompatibility Antigens. Therefore, even the perfect HLA match does not represent the optimal genetic match between donors and recipients in HSCT. In addition to the HLA complex other genetic systems operate and affect the outcome of HSCT. These include minor histocompatibility systems (Martin P. Applicability of matching for minor histocompatibility antigens in human bone marrow transplantation. In: Roopenian DC, Simpson E, editors. Minor histocompatibility antigens: From the laboratory to the clinic. Georgetown: Landis Bioscience; 2000. p. 97-103) (inducing bona fide allogeneic responses) as well as a series of functional polymorphisms in cytokines and chemokines and receptors genes (Transplantation 1997;64:553). Among the items affecting the outcome of HSCT the incidence and severity of infections have an important impact. Polymorphisms of genes controlling both arms of the immune responses to pathogens (innate versus cognate) are strong candidates for susceptibility factors to infection in allogeneic transplantation. These include the MHC alleles (HLA class I, class II, MIC) CD1, Toll and TLR genes MBP, MPO genes, ...). In addition to the NK alloreactivity induced by HLA class I epitopes mismatching (a common situation in HSCT) variations in the genotype of the KIR genes (Tissue Antigens 2001;57:358) may also be encountered between the donor and the recipient leading to potentially harmful or beneficial combinations. An integrated knowledge of the role and hierarchy of the most important genetic factors (MHC and non-MHC) will provide the rationale for a comprehensive matching in HSCT (Curr Opin Hematol 3 (1996) 416). This short review provides a panorama of this strategic issue for further development of HSCT.

  16. Late cardiovascular complications after hematopoietic cell transplantation.

    PubMed

    Chow, Eric J; Wong, Kenneth; Lee, Stephanie J; Cushing-Haugen, Kara L; Flowers, Mary E D; Friedman, Debra L; Leisenring, Wendy M; Martin, Paul J; Mueller, Beth A; Baker, K Scott

    2014-06-01

    The authors sought to better understand the combined effects of pretransplant, transplant, and post-transplant factors in determining risks of serious cardiovascular disease after hematopoietic cell transplantation (HCT). Hospitalizations and deaths associated with serious cardiovascular outcomes were identified among 1379 Washington State residents who received HCT (57% allogeneic and 43% autologous) at a single center from 1985 to 2005, survived ≥ 2 years, and followed through 2008. Using a nested case-cohort design, relationships (hazard ratios [HRs]) between potential risk factors and outcomes were examined among affected survivors and a randomly selected subcohort (N = 509). After 7.0 years of median follow-up (range, 2.0 to 23.7), the 10-year cumulative incidence of ischemic heart disease, cardiomyopathy, stroke, and all-cause cardiovascular death was 3.8%, 6.0%, 3.5%, and 3.7%, respectively. In multivariable analysis, increased pretransplant anthracycline was associated with cardiomyopathy. Active chronic graft-versus-host disease was associated with cardiovascular death (HR, 4.0; 95% confidence interval, 1.1 to 14.7); risk was otherwise similar between autologous versus allogeneic HCT recipients. Independent of therapeutic exposures, pretransplant smoking, hypertension, dyslipidemia, diabetes, and obesity conferred additional risk of all outcomes except stroke (HR ≥ 1.5 for each additional risk factor, P < .03). Hypertension and dyslipidemia at 1 year with persistence of these conditions 2 or more years after HCT also were associated with independent risks of multiple outcomes. HCT survivors with preexisting or newly developed and persistent cardiovascular risk factors remain at greater risk of subsequent serious cardiovascular disease compared with other survivors, independent of chemo- and radiotherapy exposures. These survivors should receive appropriate follow-up and be considered for primary intervention. Copyright © 2014 American Society for

  17. Salvage Second Hematopoietic Cell Transplantation in Myeloma

    PubMed Central

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

    2013-01-01

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

  18. Angiogenesis after transplantation of auto- and allogenic cells.

    PubMed

    Fatkhudinov, T Kh; Bol'shakova, G B; Komissarova, S V; Arutyunyan, I V; Rzhaninova, A A; Goldstein, D V

    2010-10-01

    Neoangiogenesis after transplantation of auto- and allogenic mononuclears and multipotent stromal cells from the bone marrow was studied on the model of inflammatory angiogenesis. Transplanted auto- and allogenic cells stimulate the formation of new blood vessels in the granulation tissue, this manifesting in an increase in the quantity and volume density of blood vessels. The most pronounced angiogenesis was observed after transplantation of allogenic mononuclears and multipotent stromal cells. It was associated with intense inflammatory infiltration, with less numerous and mature collagen fibers in the granulation tissue. Injection of allogenic cells led to stimulation and chronization of inflammation, infiltration with inflammatory and poorly differentiated cells, and more pronounced and lasting angiogenesis. However, neither auto-, nor allogenic transplanted labeled cells were detected in the walls of new blood vessels. Hence, it seems that bone marrow mononuclears and multipotent stromal cells stimulated angiogenesis mainly at the expense of production of angiogenic factors, and after transplantation of allogenic cells also by stimulating the inflammation.

  19. Luminex® and Its Applications for Solid Organ Transplantation, Hematopoietic Stem Cell Transplantation, and Transfusion†

    PubMed Central

    Lachmann, Nils; Todorova, Kremena; Schulze, Harald; Schönemann, Constanze

    2013-01-01

    Summary The detection of antibodies against the human leukocyte antigen (HLA) complex has become indispensable in every clinical practice. The development of solid-phase assays like the Luminex allows the standardized measurement of anti-HLA antibodies (HLAab) with high sensitivity, albeit the relevance for some clinical settings remains a matter of debate. In this review we aim to describe the principle of Luminex-based antibody detection, including two modifications that allow identifying solely complement-activating antibodies. We then describe three applications for Luminex: i) detection of HLAab preceding solid-organ transplantation and monitoring of donor-specific antibodies posttransplant as a risk factor for antibody-mediated rejection; ii) presence of HLAab in recipients as a risk for graft failure in hematopoietic stem cell transplantation, especially in haploidentical or mismatched transplantations; iii) role of HLAab in blood transfusion including refractory thrombocytopenia and selection of suitable platelet donors, transfusion-related lung injury after plasma transfusion, and immunization against HLA after red blood cell transfusion despite leukodepletion. Although the Luminex platform constitutes a potent technology for HLA antibody detection, some drawbacks require the well-educated analysis and interpretation of data in critical cases. In addition, Luminex has become an important tool to identify clinically relevant antibodies. PMID:23922543

  20. Promising treatment results with blood brain barrier disruption (BBBD) based immunochemotherapy combined with autologous stem cell transplantation (ASCT) in patients with primary central nervous system lymphoma (PCNSL).

    PubMed

    Kuitunen, Hanne; Tokola, Susanna; Siniluoto, Topi; Isokangas, Matti; Sonkajärvi, Eila; Alahuhta, Seppo; Turpeenniemi-Hujanen, Taina; Jantunen, Esa; Nousiainen, Tapio; Vasala, Kaija; Kuittinen, Outi

    2017-01-01

    Primary central nervous system lymphoma (PCNSL) is a rare brain tumour with a dismal prognosis. Several phase II studies with high-dose methotrexate-based regimens have shown promising early results, but in all hospital-based data published so far, the disease outcome has been poor. Patients with relapsed or refractory disease have a dismal prognosis. We performed retrospective analysis to evaluate results and tolerabilities of BBBD therapy in combination with high-dose therapy supported by autologous stem cell transplantation. We analysed 25 patients (age range: 40-71 years) who were treated in first or second line with BBBD therapy. When we started BBBD treatment, patients had relapsed or refractory PCNSL or they did not tolerate Bonn-like therapy. In recent years, some of the patients were treated in first line. We found promising response rates. Altogether 19 (76 %) of the patients achieved a complete response (CR). Two-year progression-free survival (PFS) and overall survival (OS) rates were 61 and 57 % respectively and the five-year OS was 47 %. Patients who were treated with a five-drug therapy had a very promising prognosis. The CR rate was 100 % in first-line therapy and 60 % in relapsed cases. These findings suggest that BBBD is a promising therapy for PCNSL, especially for patients in first line, but also for patients with relapsed or refractory disease after conventional chemotherapy, who commonly have a very poor prognosis. Treatment-related toxicity was generally manageable. Thus, BBBD followed by ASCT could be a treatment of choice in transplant-eligible patients with PCNSL.

  1. Modeling the Chagas’ disease after stem cell transplantation

    NASA Astrophysics Data System (ADS)

    Galvão, Viviane; Miranda, José Garcia Vivas

    2009-04-01

    A recent model for Chagas’ disease after stem cell transplantation is extended for a three-dimensional multi-agent-based model. The computational model includes six different types of autonomous agents: inflammatory cell, fibrosis, cardiomyocyte, proinflammatory cytokine tumor necrosis factor- α, Trypanosoma cruzi, and bone marrow stem cell. Only fibrosis is fixed and the other types of agents can move randomly through the empty spaces using the three-dimensional Moore neighborhood. Bone marrow stem cells can promote apoptosis in inflammatory cells, fibrosis regression and can differentiate in cardiomyocyte. T. cruzi can increase the number of inflammatory cells. Inflammatory cells and tumor necrosis factor- α can increase the quantity of fibrosis. Our results were compared with experimental data giving a fairly fit and they suggest that the inflammatory cells are important for the development of fibrosis.

  2. Impact of Pretransplantation Indices in Hematopoietic Stem Cell Transplantation: Knowledge of Center-Specific Outcome Data Is Pivotal before Making Index-Based Decisions.

    PubMed

    Törlén, Johan; Remberger, Mats; Le Blanc, Katarina; Ljungman, Per; Mattsson, Jonas

    2017-04-01

    Outcome after allogeneic hematopoietic stem cell transplantation is influenced by patient comorbidity, disease type, and status before treatment. We performed a retrospective study involving 521 consecutive adult hematopoietic stem cell transplantation patients who underwent transplantation for hematological malignancy at our center from 2000 to 2012 to compare the predictive value of the hematopoietic cell transplantation-specific comorbidity index (HCT-CI) and the disease risk index (DRI) for overall survival and transplantation-related mortality. Patients in the highest HCT-CI risk group (HCT-CI score ≥3) had a lower 5-year overall survival rate (50%) than the low-risk group (63%; P < .01). Subset analysis of donor origin showed greater 5-year overall survival in siblings than in matched unrelated donors, regardless of HCT-CI score (eg, 67% 5-year overall survival in siblings despite an HCT-CI score of >6 [n = 9]). Five-year overall survival in the highest DRI risk group was significantly poorer (44%) than in the low-risk group (63%; P < .01). Both indices failed to predict differences in transplantation-related mortality (HCT-CI, P = .54; DRI, P = .17). We conclude that HCT-CI and DRI were predictive of overall survival in our patient population. Even so, our data show that different patient groups may have different outcomes despite sharing the same index risk group and that indices should, therefore, be evaluated according to local data before clinical implementation at the single-center level.

  3. Autologous hematopoietic stem cell transplantation for pediatric multiple sclerosis: a registry-based study of the Autoimmune Diseases Working Party (ADWP) and Pediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT).

    PubMed

    Burman, J; Kirgizov, K; Carlson, K; Badoglio, M; Mancardi, G L; De Luca, G; Casanova, B; Ouyang, J; Bembeeva, R; Haas, J; Bader, P; Snowden, J; Farge, D

    2017-03-20

    Autologous hematopoietic stem cell transplantation (aHSCT) is a promising therapy for multiple sclerosis (MS), which has mainly been used in adults. The purpose of this study was to investigate efficacy and adverse events of aHSCT in the treatment of children with MS using data from the European Society for Blood and Marrow Transplantation registry. Twenty-one patients with a median follow-up time of 2.8 years could be identified. PFS at 3 years was 100%, 16 patients improved in expanded disability status scale score and only 2 patients experienced a clinical relapse. The procedure was generally well tolerated and only two instances of severe transplant-related toxicity were recorded. There was no treatment-related mortality, although one patient needed intensive care. aHSCT may be a therapeutic option for children with disease that does not respond to standard care.Bone Marrow Transplantation advance online publication, 20 March 2017; doi:10.1038/bmt.2017.40.

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

    PubMed

    Geisler, William M; Corey, Lawrence

    2002-03-27

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

  5. Immune Tolerance for Autoimmune Disease and Cell Transplantation

    PubMed Central

    Luo, Xunrong; Miller, Stephen D.; Shea, Lonnie D.

    2016-01-01

    The undesired destruction of healthy cells, either endogenous or transplanted, by the immune system results in the loss of tissue function or limits strategies to restore tissue function. Current therapies typically involve non-specific immunosuppression that may prevent the appropriate response to an antigen, thereby decreasing humoral immunity and increasing the risks of patient susceptibility to opportunistic infections, viral reactivation, and neoplasia. The induction of antigen-specific immunological tolerance to block undesired immune responses to self- or allogeneic antigens, while maintaining the integrity of the remaining immune system, has the potential to transform the current treatment of autoimmune disease and serve as a key enabling technology for therapies based on cell transplantation. PMID:26928211

  6. Haematopoietic cell transplantation in the treatment of sickle cell disease.

    PubMed

    Atkins, Robert C; Walters, Mark C

    2003-12-01

    Allogeneic haematopoietic cell transplantation (HCT) is presently the only treatment which offers the possibility of a cure for patients with sickle cell disease (SCD). While approximately 84% of patients survive disease-free after human leukocyte antigen (HLA)-identical sibling donor HCT, this therapy has traditionally been reserved for patients who have suffered serious complications due to the risk of transplant-related morbidity and mortality. Typically, these sickle-related complications have included recurrent episodes of acute chest syndrome, recurrent vaso-occlusive episodes and stroke. The future of HCT for haemoglobinopathies undoubtedly will evolve as transplant-related complications are reduced and as the process of selecting patients for HCT is refined.

  7. The Evolving Roles of Memory Immune Cells in Transplantation.

    PubMed

    Chen, Wenhao; Ghobrial, Rafik M; Li, Xian C

    2015-10-01

    Memory cells are the products of immune responses but also exert significant impact on subsequent immunity and immune tolerance, thus placing them in a unique position in transplant research. Memory cells are heterogeneous, including not only memory T cells but also memory B cells and innate memory cells. Memory cells are a critical component of protective immunity against invading pathogens, especially in immunosuppressed patients, but they also mediate graft loss and tolerance resistance. Recent studies suggest that some memory cells unexpectedly act as regulatory cells, promoting rather than hindering transplant survival. This functional diversity makes therapeutic targeting of memory cells a challenging task in transplantation. In this article, we highlight recent advances in our understanding of memory cells, focusing on diversity of memory cells and mechanisms involved in their induction and functions. We also provide a broad overview on the challenges and opportunities in targeting memory cells in the induction of transplant tolerance.

  8. The evolving roles of memory immune cells in transplantation

    PubMed Central

    Chen, Wenhao; Ghobrial, Rafik M.; Li, Xian C.

    2015-01-01

    Memory cells are the products of immune responses but also exert significant impact on subsequent immunity and immune tolerance, thus placing them in a unique position in transplant research. Memory cells are heterogeneous, including not only memory T cells but also memory B cells and innate memory cells. Memory cells are a critical component of protective immunity against invading pathogens, especially in immunosuppressed patients, but they also mediate graft loss and tolerance resistance. Recent studies suggest that some memory cells unexpectedly act as regulatory cells, promoting rather than hindering transplant survival. This functional diversity makes therapeutic targeting of memory cells a challenging task in transplantation. In this article we highlight recent advances in our understanding of memory cells, focusing on diversity of memory cells and mechanisms involved in their induction and functions. We also provide a broad overview on the challenges and opportunities in targeting memory cells in the induction of transplant tolerance. PMID:26102615

  9. Hematopoietic stem cell transplantation for osteopetrosis.

    PubMed

    Steward, Colin G

    2010-02-01

    Osteopetrosis is the generic name for a group of diseases caused by deficient formation or function of osteoclasts, inherited in either autosomal recessive or dominant fashion. Osteopetrosis varies in severity from a disease that may kill infants to an incidental radiological finding in adults. It is increasingly clear that prognosis is governed by which gene is affected, making detailed elucidation of the cause of the disease a critical component of optimal care, including the decision on whether hematopoietic stem cell transplantation is appropriate. This article reviews the characteristics and management of osteopetrosis.

  10. Stem cell transplantation in multiple sclerosis.

    PubMed

    Uccelli, Antonio; Mancardi, Gianluigi

    2010-06-01

    The recent advances in our understanding of stem cell biology, the availability of innovative techniques that allow large-scale acquisition of stem cells, and the increasing pressure from the multiple sclerosis (MS) patient community seeking tissue repair strategies have launched stem cell treatments as one of the most exciting and difficult challenges in the MS field. Here, we provide an overview of the current status of stem cell research in MS focusing on secured actuality, reasonable hopes and unrealistic myths. Results obtained from small clinical studies with transplantation of autologous hematopoietic stem cells have demonstrated that this procedure is feasible and possibly effective in severe forms of MS but tackles exclusively inflammation without affecting tissue regeneration. Results from preclinical studies with other adult stem cells such as mesenchymal stem cells and neural precursor cells have shown that they may be a powerful tool to regulate pathogenic immune response and foster tissue repair through bystander mechanisms with limited cell replacement. However, the clinical translation of these results still requires careful evaluation. Current experimental evidence suggests that the sound clinical exploitation of stem cells for MS may lead to novel strategies aimed at blocking uncontrolled inflammation, protecting neurons and promoting remyelination but not at restoring the chronically deranged neural network responsible for irreversible disability typical of the late phase of MS.

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

    PubMed

    Osakada, Fumitaka; Hirami, Yasuhiko; Takahashi, Masayo

    2010-01-01

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

  12. Haploidentical Stem Cell Transplantation in Adult Haematological Malignancies

    PubMed Central

    Parmesar, Kevon; Raj, Kavita

    2016-01-01

    Haematopoietic stem cell transplantation is a well-established treatment option for both hematological malignancies and nonmalignant conditions such as aplastic anemia and haemoglobinopathies. For those patients lacking a suitable matched sibling or matched unrelated donor, haploidentical donors are an alternative expedient donor pool. Historically, haploidentical transplantation led to high rates of graft rejection and GVHD. Strategies to circumvent these issues include T cell depletion and management of complications thereof or T replete transplants with GVHD prophylaxis. This review is an overview of these strategies and contemporaneous outcomes for hematological malignancies in adult haploidentical stem cell transplant recipients. PMID:27313619

  13. Immunity to Infections after Haploidentical Hematopoietic Stem Cell Transplantation

    PubMed Central

    Aversa, Franco; Prezioso, Lucia; Manfra, Ilenia; Galaverna, Federica; Spolzino, Angelica; Monti, Alessandro

    2016-01-01

    The advantage of using a Human Leukocyte Antigen (HLA)-mismatched related donor is that almost every patient who does not have an HLA-identical donor or who urgently needs hematopoietic stem cell transplantation (HSCT) has at least one family member with whom shares one haplotype (haploidentical) and who is promptly available as a donor. The major challenge of haplo-HSCT is intense bi-directional alloreactivity leading to high incidences of graft rejection and graft-versus-host disease (GVHD). Advances in graft processing and pharmacologic prophylaxis of GVHD have reduced these risks and have made haplo-HSCT a viable alternative for patients lacking a matched donor. Indeed, the haplo-HSCT has spread to centers worldwide even though some centers have preferred an approach based on T cell depletion of G-CSF-mobilized peripheral blood progenitor cells (PBPCs), others have focused on new strategies for GvHD prevention, such as G-CSF priming of bone marrow and robust post-transplant immune suppression or post-transplant cyclophosphamide (PTCY). Today, the graft can be a megadose of T-cell depleted PBPCs or a standard dose of unmanipulated bone marrow and/or PBPCs. Although haplo-HSCT modalities are based mainly on high intensity conditioning regimens, recently introduced reduced intensity regimens (RIC) showed promise in decreasing early transplant-related mortality (TRM), and extending the opportunity of HSCT to an elderly population with more comorbidities. Infections are still mostly responsible for toxicity and non-relapse mortality due to prolonged immunosuppression related, or not, to GVHD. Future challenges lie in determining the safest preparative conditioning regimen, minimizing GvHD and promoting rapid and more robust immune reconstitution. PMID:27872737

  14. Stem cell research in cell transplantation: sources, geopolitical influence, and transplantation.

    PubMed

    Eve, David J; Fillmore, Randolph W; Borlongan, Cesar V; Sanberg, Paul R

    2010-01-01

    If the rapidly progressing field of stem cell research reaches its full potential, successful treatments and enhanced understanding of many diseases are the likely results. However, the full potential of stem cell science will only be reached if all possible avenues can be explored and on a worldwide scale. Until 2009, the US had a highly restrictive policy on obtaining cells from human embryos and fetal tissue, a policy that pushed research toward the use of adult-derived cells. Currently, US policy is still in flux, and retrospective analysis does show the US lagging behind the rest of the world in the proportional increase in embryonic/fetal stem cell research. The majority of US studies being on either a limited number of cell lines, or on cells derived elsewhere (or funded by other sources than Federal) rather than on freshly isolated embryonic or fetal material. Neural, mesenchymal, and the mixed stem cell mononuclear fraction are the most commonly investigated types, which can generally be classified as adult-derived stem cells, although roughly half of the neural stem cells are fetal derived. Other types, such as embryonic and fat-derived stem cells, are increasing in their prominence, suggesting that new types of stem cells are still being pursued. Sixty percent of the reported stem cell studies involved transplantation, of which over three quarters were allogeneic transplants. A high proportion of the cardiovascular systems articles were on allogeneic transplants in a number of different species, including several autologous studies. A number of pharmaceutical grade stem cell products have also recently been tested and reported on. Stem cell research shows considerable promise for the treatment of a number of disorders, some of which have entered clinical trials; over the next few years it will be interesting to see how these treatments progress in the clinic.

  15. Stem cell transplantation therapy for multifaceted therapeutic benefits after stroke.

    PubMed

    Wei, Ling; Wei, Zheng Z; Jiang, Michael Qize; Mohamad, Osama; Yu, Shan Ping

    2017-03-18

    One of the exciting advances in modern medicine and life science is cell-based neurovascular regeneration of damaged brain tissues and repair of neuronal structures. The progress in stem cell biology and creation of adult induced pluripotent stem (iPS) cells has significantly improved basic and pre-clinical research in disease mechanisms and generated enthusiasm for potential applications in the treatment of central nervous system (CNS) diseases including stroke. Endogenous neural stem cells and cultured stem cells are capable of self-renewal and give rise to virtually all types of cells essential for the makeup of neuronal structures. Meanwhile, stem cells and neural progenitor cells are well-known for their potential for trophic support after transplantation into the ischemic brain. Thus, stem cell-based therapies provide an attractive future for protecting and repairing damaged brain tissues after injury and in various disease states. Moreover, basic research on naïve and differentiated stem cells including iPS cells has markedly improved our understanding of cellular and molecular mechanisms of neurological disorders, and provides a platform for the discovery of novel drug targets. The latest advances indicate that combinatorial approaches using cell based therapy with additional treatments such as protective reagents, preconditioning strategies and rehabilitation therapy can significantly improve therapeutic benefits. In this review, we will discuss the characteristics of cell therapy in different ischemic models and the application of stem cells and progenitor cells as regenerative medicine for the treatment of stroke.

  16. Current indication for hematopoietic cell transplantation in adults.

    PubMed

    Okamoto, Shinichiro

    2017-06-30

    With advances in transplantation technology and supportive care practices, hematopoietic cell transplantation (HCT) has become relatively safer and the applicability of HCT continues to expand. However, appropriate selection of transplant candidates remains challenging. Identifying adult patients who may benefit from HCT involves consideration of patient and disease factors, including overall health, prior therapies, age, comorbidity, and disease/disease risk. The eligibility of transplants should be decided on a case by case basis, based upon a risk-benefit assessment. The advent of the tools for assessing patient factors such as HCT-specific comorbidity index and disease factors such as disease risk index serve as assets for the decision-making process. Besides those approaches, psychosocial assessment to know the candidates' personalities and related issues are crucial in order to maximize patients' participation in their own care and to lay the foundation for a successful return to their personal and professional life after HCT. Copyright © 2017 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.

  17. Effects of dermal multipotent cell transplantation on skin wound healing.

    PubMed

    Chunmeng, Shi; Tianmin, Cheng; Yongping, Su; Xinze, Ran; Yue, Mai; Jifu, Qu; Shufen, Lou; Hui, Xu; Chengji, Luo

    2004-09-01

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

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

    PubMed

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

    2005-08-01

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

  19. Regulating activation of transplanted cells controls tissue regeneration

    PubMed Central

    Hill, Elliott; Boontheekul, Tanyarut; Mooney, David J.

    2006-01-01

    Current approaches to tissue regeneration are limited by the death of most transplanted cells and/or resultant poor integration of transplanted cells with host tissue. We hypothesized that transplanting progenitor cells within synthetic microenvironments that maintain viability, prevent terminal differentiation, and promote outward migration would significantly enhance their repopulation and regeneration of damaged host tissue. This hypothesis was addressed in the context of muscle regeneration by transplanting satellite cells to muscle laceration sites on a delivery vehicle releasing factors that induce cell activation and migration (hepatocyte growth factor and fibroblast growth factor 2) or transplantation on materials lacking factor release. Controls included direct cell injection into muscle, the implantation of blank scaffolds, and scaffolds releasing factors without cells. Injected cells demonstrated a limited repopulation of damaged muscle and led to a slight improvement in muscle regeneration, as expected. Delivery of cells on scaffolds that did not promote migration resulted in no improvement in muscle regeneration. Strikingly, delivery of cells on scaffolds that promoted myoblast activation and migration led to extensive repopulation of host muscle tissue and increased the regeneration of muscle fibers at the wound and the mass of the injured muscle. This previously undescribed strategy for cell transplantation significantly enhances muscle regeneration from transplanted cells and may be broadly applicable to the various tissues and organ systems in which provision and instruction of a cell population competent to participate in regeneration may be clinically useful. PMID:16477029

  20. Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia: Time to Move Toward a Minimal Residual Disease-Based Definition of Complete Remission?

    PubMed

    Araki, Daisuke; Wood, Brent L; Othus, Megan; Radich, Jerald P; Halpern, Anna B; Zhou, Yi; Mielcarek, Marco; Estey, Elihu H; Appelbaum, Frederick R; Walter, Roland B

    2016-02-01

    Patients with acute myeloid leukemia (AML) who are in morphologic complete remission are typically considered separately from patients with active disease (ie, ≥ 5% marrow blasts by morphology) in treatment algorithms for allogeneic hematopoietic cell transplantation (HCT), which implies distinct outcomes for these two groups. It is well recognized that the presence of minimal residual disease (MRD) at the time of transplantation is associated with adverse post-HCT outcome for those patients in morphologic remission. This effect of pre-HCT MRD prompted us to compare outcomes in consecutive patients in MRD-positive remission with patients with active AML who underwent myeloablative allogeneic HCT at our institution. We retrospectively studied 359 consecutive adults with AML who underwent myeloablative allogeneic HCT from a peripheral blood or bone marrow donor between 2006 and 2014. Pre-HCT disease staging included 10-color multiparametric flow cytometry on bone marrow aspirates in all patients. Any level of residual disease was considered to be MRD positive. Three-year relapse estimates were 67% in 76 patients in MRD-positive morphologic remission and 65% in 48 patients with active AML compared with 22% in 235 patients in MRD-negative remission. Three-year overall survival estimates were 26%, 23%, and 73% in these three groups, respectively. After multivariable adjustment, MRD-negative remission status remained statistically significantly associated with longer overall and progression-free survival as well as lower risk of relapse compared with MRD-positive morphologic remission status or having active disease, with similar outcomes between the latter two groups. The similarities in outcomes between patients in MRD-positive morphologic remission and those with active disease at the time of HCT support the use of treatment algorithms that use MRD- rather than morphology-based disease assessments. © 2015 by American Society of Clinical Oncology.

  1. Autologous Stem Cell Transplantation in Patients With Multiple Myeloma: An Activity-based Costing Analysis, Comparing a Total Inpatient Model Versus an Early Discharge Model.

    PubMed

    Martino, Massimo; Console, Giuseppe; Russo, Letteria; Meliado', Antonella; Meliambro, Nicola; Moscato, Tiziana; Irrera, Giuseppe; Messina, Giuseppe; Pontari, Antonella; Morabito, Fortunato

    2017-08-01

    Activity-based costing (ABC) was developed and advocated as a means of overcoming the systematic distortions of traditional cost accounting. We calculated the cost of high-dose chemotherapy and autologous stem cell transplantation (ASCT) in patients with multiple myeloma using the ABC method, through 2 different care models: the total inpatient model (TIM) and the early-discharge outpatient model (EDOM) and compared this with the approved diagnosis related-groups (DRG) Italian tariffs. The TIM and EDOM models involved a total cost of €28,615.15 and €16,499.43, respectively. In the TIM model, the phase with the greatest economic impact was the posttransplant (recovery and hematologic engraftment) with 36.4% of the total cost, whereas in the EDOM model, the phase with the greatest economic impact was the pretransplant (chemo-mobilization, apheresis procedure, cryopreservation, and storage) phase, with 60.4% of total expenses. In an analysis of each episode, the TIM model comprised a higher absorption than the EDOM. In particular, the posttransplant represented 36.4% of the total costs in the TIM and 17.7% in EDOM model, respectively. The estimated reduction in cost per patient using an EDOM model was over €12,115.72. The repayment of the DRG in Calabrian Region for the ASCT procedure is €59,806. Given the real cost of the transplant, the estimated cost saving per patient is €31,190.85 in the TIM model and €43,306.57 in the EDOM model. In conclusion, the actual repayment of the DRG does not correspond to the real cost of the ASCT procedure in Italy. Moreover, using the EDOM, the cost of ASCT is approximately the half of the TIM model. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Twenty-five years of peripheral blood stem cell transplantation.

    PubMed

    Körbling, Martin; Freireich, Emil J

    2011-06-16

    Peripheral blood stem cell transplantation (PBSCT) is the most common transplantation procedure performed in medicine. Its clinical introduction in 1986 replaced BM as a stem-cell source to approximately 100% in the autologous and to approximately 75% in the allogeneic transplantation setting. This historical overview provides a brief insight into the discovery of circulating hematopoietic stem cells in the early 1960s, the development of apheresis technology, the discovery of hematopoietic growth factors and small molecule CXCR4 antagonist for stem- cell mobilization, and in vivo experimental transplantation studies that eventually led to clinical PBSCT. Also mentioned are the controversies surrounding the engraftment potential of circulating stem cells before acceptance as a clinical modality. Clinical trials comparing the outcome of PBSCT with BM transplantation, registry data analyses, and the role of the National Marrow Donor Program (NMDP) in promoting unrelated blood stem-cell donation are addressed.

  3. Neural Stem Cell Transplantation and CNS Diseases.

    PubMed

    Gonzalez, Rodolfo; Hamblin, Milton H; Lee, Jean-Pyo

    2016-01-01

    In neurological disorders, pathological lesions in the central nervous system (CNS) may be globally dispersed throughout the brain or localized to specific regions. Although native neural stem cells (NSCs) are present in the adult mammalian brain, intrinsic self-repair of injured adult CNS tissue is inadequate or ineffective. The brain's poor regenerative ability may be due to the fact that NSCs are restricted to discrete locations, are few in number, or are surrounded by a microenvironment that does not support neuronal differentiation. Therapeutic potential of NSC transplantation in CNS diseases characterized by global degeneration requires that gene products and/or replaced cells be widely distributed. Global degenerative CNS diseases include inherited pediatric neurodegenerative diseases (inborn errors of metabolism, including lysosomal storage disorders (LSDs), such as Tay-Sachs-related Sandhoff disease), hypoxic or ischemic encephalopathy, and some adult CNS diseases (such as multiple sclerosis). Both mouse and human NSCs express many chemokines and chemokine receptors (including CXCR4 and adhesion molecules, such as integrins, selectins, and immunoglobulins) that mediate homing to sources of inflammatory chemokines, such as SDF-1α. In mammalian brains of all ages, NSCs may be attracted even at a great distance to regions of neurodegeneration. Consequently, NSC transplantation presents a promising strategy for treating many CNS diseases.

  4. Gastrointestinal and hepatic complications of hematopoietic stem cell transplantation

    PubMed Central

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

    2012-01-01

    Recognition and management of gastrointestinal and hepatic complications of hematopoietic stem cell transplantation has gained increasing importance as indications and techniques of transplantation have expanded in the last few years. The transplant recipient is at risk for several complications including conditioning chemotherapy related toxicities, infections, bleeding, sinusoidal obstruction syndrome, acute and chronic graft-versus-host disease (GVHD) as well as other long-term problems. The severity and the incidence of many complications have improved in the past several years as the intensity of conditioning regimens has diminished and better supportive care and GVHD prevention strategies have been implemented. Transplant clinicians, however, continue to be challenged with problems arising from human leukocyte antigen-mismatched and unrelated donor transplants, expanding transplant indications and age-limit. This review describes the most commonly seen transplant related complications, focusing on their pathogenesis, differential diagnosis and management. PMID:22563164

  5. Severe sepsis in hematopoietic stem cell transplant recipients*.

    PubMed

    Kumar, Gagan; Ahmad, Shahryar; Taneja, Amit; Patel, Jayshil; Guddati, Achuta Kumar; Nanchal, Rahul

    2015-02-01

    Severe sepsis requires timely management and has high mortality if care is delayed. Hematopoietic stem cell transplant recipients are more likely to be immunocompromised and are predisposed to serious infections. Reports of outcomes of severe sepsis in this population are limited to data from single, tertiary care centers, and national outcomes data are missing. Retrospective analysis of an administrative database. Twenty percent of community hospitals in United States, excluding federal hospitals. Patients with severe sepsis. None. We used International Classification of Diseases, 9th Edition, Clinical Modification codes indicating the presence of sepsis and organ system failure to identify hospitalizations for severe sepsis between 2000 and 2008. We also used International Classification of Diseases, 9th Edition, Clinical Modification codes to identify hematopoietic stem cell transplant recipients. We compared outcomes of hematopoietic stem cell transplant recipients with severe sepsis during engraftment and subsequent admissions with a non-hematopoietic stem cell transplant cohort and excluded solid-organ transplantation from this cohort. We used mixed effect, multivariate logistic regression modeling with propensity score adjustment to examine factors associated with mortality of severe sepsis in hematopoietic stem cell transplant recipients. A total of 21,898 hematopoietic stem cell transplant recipients with severe sepsis were identified. The frequency of severe sepsis in hematopoietic stem cell transplant recipients was five times higher when compared with the non-hematopoietic stem cell transplant cohort. The unadjusted mortality was 32.9% in non-hematopoietic stem cell transplant cohort, which was similar to autologous hematopoietic stem cell transplant recipients (30.1%) and those who did not develop graft-versus-host disease (35%). Mortality was significantly higher in allogeneic transplants (55.1%, p < 0.001) and in those who developed graft

  6. [Aspergillus galactomannan detection in allogenic hematopoietic cell transplantation].

    PubMed

    Rovira Tarrats, Montserrat; Puig de la Bellacasa, Jorge

    2003-09-01

    Invasive aspergillosis has become the leading cause of death after allogeneic hematopoietic stem cell transplantation. This is partially due to the lack of a prompt diagnosis. Recently the detection of Aspergillus galactomannan antigen by means an ELISA technique in serum has been described. The objective of this study was to validate its usefulness in the allogeneic hematopoietic stem cell transplantation setting.

  7. Hematopoietic Stem Cell Transplantation for Hematologic Malignancies in Older Adults: Geriatric Principles in the Transplant Clinic

    PubMed Central

    Wildes, Tanya M.; Stirewalt, Derek L.; Medeiros, Bruno; Hurria, Arti

    2014-01-01

    Hematopoietic cell transplantation (HCT) provides a life-prolonging or potentially curative treatment option for patients with hematologic malignancies. Given the high transplant-related morbidity, these treatment strategies were initially restricted to younger patients, but are increasingly being used in older adults. The incidence of most hematologic malignancies increases with age; with the aging of the population, the number of potential older candidates for HCT increases. Autologous HCT (auto-HCT) in older patients may confer a slightly increased risk of specific toxicities (such as cardiac toxicities and mucositis) and have modestly lower effectiveness (in the case of lymphoma). However, auto-HCT remains a feasible, safe, and effective therapy for selected older adults with multiple myeloma and lymphoma. Similarly, allogeneic transplant (allo-HCT) is a potential therapeutic option for selected older adults, although fewer data exist on allo-HCT in older patients. Based on currently available data, age alone is not the best predictor of toxicity and outcomes; rather, the comorbidities and functional status of the older patient are likely better predictors of toxicity than chronologic age in both the autologous and allogeneic setting. A comprehensive geriatric assessment (CGA) in older adults being considered for either an auto-HCT or allo-HCT may identify additional problems or geriatric syndromes, which may not be detected during the standard pretransplant evaluation. Further research is needed to establish the utility of CGA in predicting toxicity and to evaluate the quality of survival in older adults undergoing HCT. PMID:24453296

  8. Sustained telomere erosion due to increased stem cell turnover during triple autologous hematopoietic stem cell transplantation.

    PubMed

    Widmann, Thomas; Kneer, Harald; König, Jochem; Herrmann, Markus; Pfreundschuh, Michael

    2008-01-01

    Telomeres cap chromosomal ends and are shortened throughout a lifetime. Additional telomere erosion has been documented during conventional chemotherapy or hematopoietic stem cell transplantation. Previous studies of stem cell transplantation reported variable amounts of telomere shortening with inconsistent results regarding the persistence of telomere shortening. Here we have prospectively studied telomere length and proliferation kinetics of hematopoietic cells in aggressive non-Hodgkin lymphoma patients who underwent a four-course high-dose chemotherapy protocol combined with triple autologous stem cell transplantation. We observed sustained telomere shortening in hematopoietic cells after triple stem cell transplantation with prolonged stem cell replication during the first year after stem cell transplantation.

  9. In Vivo Bioimaging Rats for Translational Research in Cell and Tissue Transplantation.

    PubMed

    Teratani, Takumi; Kobayashi, Eiji

    2012-01-01

    The rat is an excellent cell transplantation model. In accordance with the innovative development of in vivo bioimaging technology, over the last decade we have been developing an engineered rat system based on transgenic technology and have been demonstrating the usefulness of the system with genetically encoded imaging probes such as fluorescent and luminescent proteins. In cooperation with the Japan Society for Organ Preservation and Medical Biology (President: Professor T. Asano), we have also been using luciferase-Tg rats for research into organ preservation and cell transplantation. In this minireview, we introduce the results obtained recently by using these powerful experimental tools during international collaboration in cell transplantation research.

  10. Kidney transplant after hematopoietic cell transplant in pediatrics: Infectious and immunosuppressive considerations.

    PubMed

    Ebens, Christen L; Smith, Angela R; Verghese, Priya S

    2017-08-01

    Pediatric patients requiring kidney transplant after hematopoietic cell transplant receive multiple courses of immunosuppression placing them at risk for infection. To elucidate potential risk factors for infection, we compared the immunosuppressive regimens and infectious complications of pediatric kidney transplant recipients at a single institution who had previously undergone hematopoietic cell transplant from different donors to similar patients reported in the literature. Among the initial four post-hematopoietic cell transplant kidney transplant patients reviewed, viremia episodes were universal, including BK virus, Epstein-Barr virus, and human herpesvirus-6, with one death from presumed BK virus encephalitis. No viremia was reported in five similar cases in the literature. Risk factors for increased infection include use of lymphodepleting serotherapy in HCT conditioning, multiple HCTs, limited immune reconstitution time between transplants, increased pre-KTx viral burden, and use of T-cell-depleting versus -suppressive induction immunosuppression for KTx. These findings suggest that pediatric post-HCT KTx recipients are at increased risk for viral infections, likely benefitting from thorough pre-KTx evaluation of immune reconstitution and preferential use of non-T-cell-depleting induction therapy for KTx. We applied these recommendations to one subsequent post-HCT patient requiring KTx at our institution with excellent outcomes one year post-KTx. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Stem cell transplantation: a treatment option for severe systemic sclerosis?

    PubMed

    van Laar, J M; Farge, D; Tyndall, A

    2008-12-01

    High-dose immunosuppressive therapy and autologous stem cell transplantation (commonly referred to as "stem cell transplantation") is an established treatment for a variety of haemato-oncological conditions. Recent studies have confirmed its potent clinical and immunological effects in rheumatic autoimmune diseases, including severe diffuse systemic sclerosis (SSc). With modifications of treatment protocols and more stringent selection of patients, the safety profile of stem cell transplantation has improved as expressed in lower treatment-related morbidity and mortality. Prospective, randomised trials are in progress in Europe and North America to compare the safety and efficacy of stem cell transplantation with conventional chemotherapy in patients with early diffuse SSc, on the premise that induction of remission in early disease can be achieved by stem cell transplantation as a means to interrupt fibrogenesis.

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

    PubMed

    Ishii, Tetsuya; Eto, Koji

    2014-09-26

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

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

    PubMed Central

    Ishii, Tetsuya; Eto, Koji

    2014-01-01

    Since 1928, human fetal tissues and stem cells have been used worldwide to treat various conditions. Although the transplantation of the fetal midbrain substantia nigra and dopaminergic neurons in patients suffering from Parkinson’s disease is particularly noteworthy, the history of other types of grafts, such as those of the fetal liver, thymus, and pancreas, should be addressed as there are many lessons to be learnt for future stem cell transplantation. This report describes previous practices and complications that led to current clinical trials of isolated fetal stem cells and embryonic stem (ES) cells. Moreover, strategies for transplantation are considered, with a particular focus on donor cells, cell processing, and the therapeutic cell niche, in addition to ethical issues associated with fetal origin. With the advent of autologous induced pluripotent stem cells and ES cells, clinical dependence on fetal transplantation is expected to gradually decline due to lasting ethical controversies, despite landmark achievements. PMID:25258662

  14. Allogeneic hematopoietic stem cell transplantation in children with sickle cell disease.

    PubMed

    Locatelli, Franco; Pagliara, Daria

    2012-08-01

    Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents the only curative treatment for sickle cell disease (SCD), being successful in around 85-90% of patients. Mortality and long-term morbidity (including infertility, gonadal failure, and chronic graft-vs.-host disease) associated with conventional approaches curtail the number of patients who undergo allo-HSCT. Recently, it has been demonstrated that cord blood is as effective as and possibly safer than bone marrow in pediatric patients with SCD. Likewise, transplant strategies based on the use of reduced-intensity regimens and the induction of mixed chimerism have been explored to decrease allo-HSCT short- and long-term complications.

  15. Composite vascularized skin/bone transplantation models for bone marrow-based tolerance studies.

    PubMed

    Ozmen, Selahattin; Ulusal, Betul G; Ulusal, Ali E; Izycki, Dariusz; Siemionow, Maria

    2006-03-01

    There is an ongoing need to understand the mechanisms of bone marrow-based allograft tolerance. This is important in clarifying the diverse variables influencing the ultimate outcome of the solid organ and composite tissue transplants. To establish bone marrow transplantation as a routine clinical application, further experimental studies should be conducted to overcome the obstacles related to the bone marrow transplantation. These obstacles include graft versus host disease, immunocompetence, and toxicity of the conditioning regimens. For these purposes, novel experimental models are needed. In an attempt to provide a reliable research tool for bone marrow-based tolerance induction studies, we introduced different experimental models of modified vascularized skin/bone marrow (VSBM) transplantation technique for tolerance induction, monitoring, and maintenance studies. In this skin/bone transplantation model, the technical feasibility of concurrent or consecutive transplantation of the combination of bilateral vascularized skin, vascularized bone marrow, or vascularized skin/bone marrow transplants was investigated. Isograft transplantations were performed between genetically identical Lewis (LEW, RT1) rats. Five different experimental designs in 5 groups of 5 animals each were studied. Group I: Bilateral vascularized skin (VS) transplantation; group II: bilateral vascularized skin/bone transplantation; group III: vascularized skin transplantation on one side and vascularized skin/bone transplantation on the contralateral side; group IV: vascularized bone transplantation on one side and vascularized skin/bone transplantation on the contralateral side; group V: vascularized bone transplantation on one side and vascularized skin transplantation on the contralateral side. Successful transplantations were performed in all groups. The survival of the isograft transplants was evaluated clinically and histologically. All skin flaps remained pink and pliable and grew new

  16. Comparison of Subcutaneous versus Intravenous Alemtuzumab for Graft-versus-Host Disease Prophylaxis with Fludarabine/Melphalan-Based Conditioning in Matched Unrelated Donor Allogeneic Stem Cell Transplantation.

    PubMed

    Patel, Khilna; Parmar, Sapna; Shah, Shreya; Shore, Tsiporah; Gergis, Usama; Mayer, Sebastian; van Besien, Koen

    2016-03-01

    The objective of this study was to compare infusion-related reactions and outcomes of using subcutaneous (subQ) alemtuzumab versus intravenous (i.v.) alemtuzumab as graft-versus-host disease (GVHD) prophylaxis for matched unrelated donor stem cell transplantations. Outcomes include incidence of cytomegalovirus (CMV)/Epstein-Barr (EBV) viremia, development of CMV disease or post-transplantation lymphoproliferative disorder, fatal infections, acute and chronic GVHD, time to engraftment, relapse rate, and survival. We conducted a retrospective study of all adult matched unrelated donor stem cell transplantations patients who received fludarabine/melphalan with subQ or i.v. alemtuzumab in combination with tacrolimus as part of their conditioning for unrelated donor transplantation at New York-Presbyterian/Weill Cornell Medical Center from January 1, 2012 to March 21, 2014. Alemtuzumab was administered at a total cumulative dose of 100 mg (divided over days -7 to -3). Forty-six patients received an unrelated donor stem cell transplantation with fludarabine/melphalan and either subQ (n = 26) or i.v. (n = 20) alemtuzumab in combination with tacrolimus. Within the evaluable population, 130 subQ and 100 i.v. alemtuzumab doses were administered. For the primary outcome, ≥grade 2 infusion-related reactions occurred in 11 (8%) versus 25 (25%) infusions in the subQ and i.v. cohorts, respectively (P = .001). Overall, 12 injections (9%) in the subQ arm versus 26 infusions (26%) in the i.v. arm experienced an infusion-related reaction of any grade (P = .001). There were no significant differences between the subQ and i.v. arms in rates of reactivation of CMV/EBV, development of CMV disease or post-transplantation lymphoproliferative disorder, fatal infections, acute and chronic GVHD, relapse, or survival. Subcutaneous administration of alemtuzumab for GVHD prophylaxis was associated with fewer infusion-related reactions compared with i.v. administration in the SCT setting

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

    PubMed

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

    2010-07-01

    Liver transplantation has been remarkably effective in the treatment in patients with end-stage liver disease. However, disparity between solid-organ supply and increased demand is the greatest limitation, resulting in longer waiting times and increase in mortality of transplant recipients. This situation creates the need to seek alternatives to orthotopic liver transplantation.Hepatocyte transplantation or liver cell transplantation has been proposed as the best method to support patients. The procedure consists of transplanting individual cells to a recipient organ in sufficient quantity to survive and restore the function. The capacity of hepatic regeneration is the biological basis of hepatocyte transplantation. This therapeutic option is an experimental procedure in some patients with inborn errors of metabolism, fulminant hepatic failure and acute and chronic liver failure, as a bridge to orthotopic liver transplantation. In the Hospital La Fe of Valencia, we performed the first hepatocyte transplantation in Spain creating a new research work on transplant program. Copyright 2009 AEC. Published by Elsevier Espana. All rights reserved.

  18. Optimisation of a quantitative polymerase chain reaction-based strategy for the detection and quantification of human herpesvirus 6 DNA in patients undergoing allogeneic haematopoietic stem cell transplantation

    PubMed Central

    Ueda, Miriam YH; Alvarenga, Paulo G; Real, Juliana M; Moreira, Eloisa de Sá; Watanabe, Aripuanã; Passos-Castilho, Ana Maria; Vescovi, Matheus; Novis, Yana; Rocha, Vanderson; Seber, Adriana; Oliveira, Jose SR; Rodrigues, Celso A; Granato, Celso FH

    2015-01-01

    Human herpesvirus 6 (HHV-6) may cause severe complications after haematopoietic stem cell transplantation (HSCT). Monitoring this virus and providing precise, rapid and early diagnosis of related clinical diseases, constitute essential measures to improve outcomes. A prospective survey on the incidence and clinical features of HHV-6 infections after HSCT has not yet been conducted in Brazilian patients and the impact of this infection on HSCT outcome remains unclear. A rapid test based on real-time quantitative polymerase chain reaction (qPCR) has been optimised to screen and quantify clinical samples for HHV-6. The detection step was based on reaction with TaqMan® hydrolysis probes. A set of previously described primers and probes have been tested to evaluate efficiency, sensitivity and reproducibility. The target efficiency range was 91.4% with linearity ranging from 10-106 copies/reaction and a limit of detection of five copies/reaction or 250 copies/mL of plasma. The qPCR assay developed in the present study was simple, rapid and sensitive, allowing the detection of a wide range of HHV-6 loads. In conclusion, this test may be useful as a practical tool to help elucidate the clinical relevance of HHV-6 infection and reactivation in different scenarios and to determine the need for surveillance. PMID:26038958

  19. Development, feasibility and compliance of a web-based system for very frequent QOL and symptom home self-assessment after hematopoietic stem cell transplantation.

    PubMed

    Bush, N; Donaldson, G; Moinpour, C; Haberman, M; Milliken, D; Markle, V; Lauson, J

    2005-02-01

    We believe that many adverse events following hematopoietic stem cell transplantation (HSCT), particularly relapse and chronic graft-versus-host disease (CGVHD), are preceded by a subclinical period of development that is accessible by frequent psychometric assessment. Documenting these associations could improve future clinical care by extending the potential window for intervention. However, conventional methods of assessing quantity of lite (QOL) in patients in their homes, typically by mailed self-assessment questionnaires, are impractical for very frequent administration. We have developed and implemented a web-based system for measuring short-term (dynamic) changes in QOL by employing brief, online, daily QOL assessments and more extensive, monthly online assessments from patients' homes. Here we report the feasibility of collecting very frequent patient home self-assessments of QOL via the web for a 52 week participation period; we detail incidence of home web access, accrual, compliance, and satisfaction with the system in an HSCT patient sample. We also describe our integrated web-systems for administering patient recruitment, scheduling, monitoring, and analysis. Our results suggest that very frequent routine collection of QOL outcomes is entirely feasible using our web-based home assessment tool, with good patient compliance and high user satisfaction. We believe our methodology shows great promise for use with other cancer and health populations.

  20. Pediatric hematology providers on referral for transplant evaluation for sickle cell disease: a regional perspective.

    PubMed

    Mikles, Bethany; Bhatia, Monica; Oyeku, Suzette O; Jin, Zhezhen; Green, Nancy S

    2014-10-01

    Hematology referral for evaluation is a key step for hematopoietic stem cell transplantation for sickle cell disease (SCD). Pediatric SCD providers in the US Northeast (New York-Mid-Atlantic and New England regions) were surveyed anonymously for perspectives and practices regarding transplant referral and compared by whether they practiced at SCD transplant centers. Data were analyzed using the Fisher exact test, χ test, and logistic regression. Half of the respondents practiced primarily at transplant sites. Most (79%) were enthusiastic about transplant for SCD and 78% had recently referred ≥1 child for evaluation. Overall, 77% limited referral to certain sickle hemoglobinopathies and 44% preferred referral for β-thalassemia to SCD. Indications selected for referral resembled current transplant criteria, plus family request or poor response to therapy. Referral for children on chronic transfusions predicted enthusiasm and prior referral. Many (66%) referred children with multiple SCD complications, even without matched sibling donors, 37% with sibling donors despite limited disease. Practitioners at transplant centers more commonly accepted event-free survival rates of ≤90% (P=0.002). Northeastern providers expressed varying enthusiasm for referral for evaluation based on eligibility, donor availability, and acceptable risk, with modestly more interest from practitioners at transplant centers. Differing provider perspectives may affect patient referral for transplant consideration.

  1. Pediatric Hematology Providers on Referral for Transplant Evaluation for Sickle Cell Disease: A Regional Perspective

    PubMed Central

    Mikles, Bethany; Bhatia, Monica; Oyeku, Suzette O.; Jin, Zhezhen; Green, Nancy S.

    2014-01-01

    Summary Hematology referral for evaluation is a key step for hematopoietic stem cell transplantation for sickle cell disease (SCD). Pediatric SCD providers in the US Northeast (New York-Mid-Atlantic and New England regions) were surveyed anony-mously for perspectives and practices regarding transplant referral and compared by whether they practiced at SCD transplant centers. Data were analyzed using the Fisher exact test, χ2 test, and logistic regression. Half of the respondents practiced primarily at transplant sites. Most (79%) were enthusiastic about transplant for SCD and 78% had recently referred ≥1 child for evaluation. Overall, 77% limited referral to certain sickle hemoglobinopathies and 44% preferred referral for β-thalassemia to SCD. Indications selected for referral resembled current transplant criteria, plus family request or poor response to therapy. Referral for children on chronic transfusions predicted enthusiasm and prior referral. Many (66%) referred children with multiple SCD complications, even without matched sibling donors, 37% with sibling donors despite limited disease. Practitioners at transplant centers more commonly accepted event-free survival rates of ≤90% (P = 0.002). North-eastern providers expressed varying enthusiasm for referral for evaluation based on eligibility, donor availability, and acceptable risk, with modestly more interest from practitioners at transplant centers. Differing provider perspectives may affect patient referral for transplant consideration. PMID:24633300

  2. Autologous hematopoietic cell transplantation in multiple sclerosis.

    PubMed

    Bell, Simon M; Sharrack, Basil; Snowden, John A

    2017-01-01

    Autologous haematopoietic cell transplantation (AHCT) is an evolving treatment avenue in multiple sclerosis (MS), which may be highly effective in controlling disease activity and improving disability. However, AHCT is associated with intrinsic toxicities and risks compared with conventional therapies. With growing experience in patient selection and treatment delivery, AHCT is increasingly considered an option in patients with aggressive disease that's responding poorly to disease modifying therapy. Areas covered: This article provides an introduction to AHCT and looks at its development as a treatment for MS over the last 20 years. It also highlights potential mechanisms of action, patient selection, and future trends for this treatment approach. Expert opinion: Currently published data suggest that AHCT's use is associated with significant reduction in MS disease activity and marked improvement in disability when used in patients with highly active relapsing remitting disease. Its long term safety and efficacy have not been fully evaluated but as increasing clinical trial data are published, its use is likely to grow. Further randomised controlled studies are needed to compare AHCT with standard disease modifying therapies and to optimise transplant regimens. Mechanistic studies may provide potential markers for response and a better understanding of disease pathogenesis.

  3. Transplantation of Heterospheroids of Islet Cells and Mesenchymal Stem Cells for Effective Angiogenesis and Antiapoptosis

    PubMed Central

    Shin, Jung-Youn; Jeong, Jee-Heon; Han, Jin; Bhang, Suk Ho; Jeong, Gun-Jae; Haque, Muhammad R.; Al-Hilal, Taslim A.; Noh, Myungkyung

    2015-01-01

    Although islet transplantation has been suggested as an alternative therapy for type 1 diabetes, there are efficiency concerns that are attributed to poor engraftment of transplanted islets. Hypoxic condition and delayed vasculogenesis induce necrosis and apoptosis of the transplanted islets. To overcome these limitations in islet transplantation, heterospheroids (HSs), which consist of rat islet cells (ICs) and human bone marrow-derived mesenchymal stem cells (hMSCs), were transplanted to the kidney and liver. The HSs cultured under the hypoxic condition system exhibited a significant increase in antiapoptotic gene expression in ICs. hMSCs in the HSs secreted angiogenic and antiapoptotic proteins. With the HS system, ICs and hMSCs were successfully located in the same area of the liver after transplantation of HSs through the portal vein, whereas the transplantation of islets and the dissociated hMSCs did not result in localization of transplanted ICs and hMSCs in the same area. HS transplantation resulted in an increase in angiogenesis at the transplantation area and a decrease in the apoptosis of transplanted ICs after transplantation into the kidney subcapsule compared with transplantation of islet cell clusters (ICCs). Insulin production levels of ICs were higher in the HS transplantation group compared with the ICC transplantation group. The HS system may be a more efficient transplantation method than the conventional methods for the treatment of type 1 diabetes. PMID:25344077

  4. [Cell transplant and regenerative stem cell therapy].

    PubMed

    Prosper, F

    2008-01-01

    The derivation of the first human embryonic stem cell lines as well as the notion of the unexpected plasticity and potential of the adult stem cells has significantly impacted the biomedical research. Many of the tissues long believe to lack any regenerative capacity has demonstrated otherwise. Patients alike physicians expectations for treatment of incurable diseases have also fuelled this field and in occasions have led to unrealistic expectations. In the next pages I review some of the tissue specific stem cells that have been used either in preclinical models or even in clinical research. Despite the effort of numerous investigators, more questions that answers remain in the field of cell therapy and only careful and independent -not biased- research will allow us to translate some of this findings into clinical application.

  5. Curative treatment for severe sickle cell disease: allogeneic transplantation.

    PubMed

    Oshrine, Benjamin; Talano, Julie-An

    2015-04-01

    Sickle cell disease is an inherited hematologic disorder that in its severe form can result in substantial morbidity and early mortality. Patients with this disorder can suffer from severe pain, lung disease, and strokes, resulting in chronic debilitating conditions, end organ dysfunction, and organ failure. The health care costs of caring for these chronically ill patients are substantial. Allogeneic transplantation is a modality that has the potential to cure these patients. To date, matched sibling donor transplantation is widely accepted as a standard of care for pediatric patients. Utilizing alternative donors for transplant is still under investigation, as is transplant for adult patients with sickle cell disease. This review focuses on the most recent data for hematopoietic cell transplantation for patients with sickle cell disease.

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

    MedlinePlus

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

  7. Cells transplanted onto the surface of the glial scar reveal hidden potential for functional neural regeneration

    PubMed Central

    Sekiya, Tetsuji; Holley, Matthew C.; Hashido, Kento; Ono, Kazuya; Shimomura, Koichiro; Horie, Rie T.; Hamaguchi, Kiyomi; Yoshida, Atsuhiro; Sakamoto, Tatsunori; Ito, Juichi

    2015-01-01

    Cell transplantation therapy has long been investigated as a therapeutic intervention for neurodegenerative disorders, including spinal cord injury, Parkinson’s disease, and amyotrophic lateral sclerosis. Indeed, patients have high hopes for a cell-based therapy. However, there are numerous practical challenges for clinical translation. One major problem is that only very low numbers of donor cells survive and achieve functional integration into the host. Glial scar tissue in chronic neurodegenerative disorders strongly inhibits regeneration, and this inhibition must be overcome to accomplish successful cell transplantation. Intraneural cell transplantation is considered to be the best way to deliver cells to the host. We questioned this view with experiments in vivo on a rat glial scar model of the auditory system. Our results show that intraneural transplantation to the auditory nerve, preceded by chondroitinase ABC (ChABC)-treatment, is ineffective. There is no functional recovery, and almost all transplanted cells die within a few weeks. However, when donor cells are placed on the surface of a ChABC-treated gliotic auditory nerve, they autonomously migrate into it and recapitulate glia- and neuron-guided cell migration modes to repair the auditory pathway and recover auditory function. Surface transplantation may thus pave the way for improved functional integration of donor cells into host tissue, providing a less invasive approach to rescue clinically important neural tracts. PMID:26080415

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

    PubMed

    Tiernan, Aubrey R; Sambanis, Athanassios

    2017-02-01

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

  9. Gene Expression Changes in the Injured Spinal Cord Following Transplantation of Mesenchymal Stem Cells or Olfactory Ensheathing Cells

    PubMed Central

    Torres-Espín, Abel; Hernández, Joaquim; Navarro, Xavier

    2013-01-01

    Transplantation of bone marrow derived mesenchymal stromal cells (MSC) or olfactory ensheathing cells (OEC) have demonstrated beneficial effects after spinal cord injury (SCI), providing tissue protection and improving the functional recovery. However, the changes induced by these cells after their transplantation into the injured spinal cord remain largely unknown. We analyzed the changes in the spinal cord transcriptome after a contusion injury and MSC or OEC transplantation. The cells were injected immediately or 7 days after the injury. The mRNA of the spinal cord injured segment was extracted and analyzed by microarray at 2 and 7 days after cell grafting. The gene profiles were analyzed by clustering and functional enrichment analysis based on the Gene Ontology database. We found that both MSC and OEC transplanted acutely after injury induce an early up-regulation of genes related to tissue protection and regeneration. In contrast, cells transplanted at 7 days after injury down-regulate genes related to tissue regeneration. The most important change after MSC or OEC transplant was a marked increase in expression of genes associated with foreign body response and adaptive immune response. These data suggest a regulatory effect of MSC and OEC transplantation after SCI regarding tissue repair processes, but a fast rejection response to the grafted cells. Our results provide an initial step to determine the mechanisms of action and to optimize cell therapy for SCI. PMID:24146830

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

    PubMed

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

    2014-12-01

    Stem cell transplantation is a generic term covering different techniques. However there is argument over the pros and cons of autologous and allogeneic transplants of mesenchymal stem cells (MSCs) for regenerative therapy. Given that the MSCs have already been proven to be safe in patients, we hypothesize that allogeneic transplantation could be more effective and cost-effective as compared to autologous transplantation specifically in older subjects who are the likely victims of degenerative diseases. This analysis is based on the scientific logic that allogeneic stem cells extracted in large numbers from young and healthy donors could be physiologically, metabolically and genetically more stable. Therefore stem cells from young donors may be expected to exhibit higher vigor in secreting trophic factors leading to activation of host tissue-specific stem cells and also be more efficient in remodeling the micro-environmental niche of damaged tissue. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. National Survey of Hematopoietic Cell Transplantation Center Personnel, Infrastructure, and Models of Care Delivery.

    PubMed

    Majhail, Navneet S; Mau, Lih-Wen; Chitphakdithai, Pintip; Payton, Tammy; Eckrich, Michael; Joffe, Steven; Lee, Stephanie J; LeMaistre, Charles F; LeRademacher, Jennifer; Loberiza, Fausto; Logan, Brent; Parsons, Susan K; Repaczki-Jones, Ramona; Robinett, Pam; Rizzo, J Douglas; Murphy, Elizabeth; Denzen, Ellen M

    2015-07-01

    Hematopoietic cell transplantation (HCT) is a complex procedure that requires availability of adequate infrastructure, personnel, and resources at transplantation centers. We conducted a national survey of transplantation centers in the United States to obtain data on their personnel, infrastructure, and care delivery models. A 42-item web-based survey was administered to medical directors of transplantation centers in the United States that reported any allogeneic HCT to the Center for International Blood and Marrow Transplant Research in 2011. The response rate for the survey was 79% for adult programs (85 of 108 centers) and 82% for pediatric programs (54 of 66 centers). For describing results, we categorized centers into groups with similar volumes based on 2010 total HCT activity (adult centers, 9 categories; pediatric centers, 6 categories). We observed considerable variation in available resources, infrastructure, personnel, and care delivery models among adult and pediatric transplantation centers. Characteristics varied substantially among centers with comparable transplantation volumes. Transplantation centers may find these data helpful in assessing their present capacity and use them to evaluate potential resource needs for personnel, infrastructure, and care delivery and in planning for growth. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

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

    PubMed

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

    2016-04-07

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

  13. Transplantation and differentiation of donor cells in the cloned pigs

    SciTech Connect

    Shimada, Arata; Tomii, Ryo; Kano, Koichiro; Nagashima, Hiroshi . E-mail: hnagas@isc.meiji.ac.jp

    2006-06-02

    The application of nuclear transfer technology is an interesting approach to investigate stem and progenitor cell transplantation therapy. If stem cells are used as a nuclear donor, donor cells can engraft into cloned animals without histocompatible problems. However, it is still uncertain whether donor cells can engraft to cloned animal and differentiate in vivo. To address this problem, we transplanted donor cells to dermal tissues of cloned pigs developed by using preadipocytes as donor cells. Preadipocytes are adipocytic progenitor which can differentiate to mature adipocytes in vitro. We showed that the donor preadipocytes were successfully transplanted into the cloned pigs without immune rejection and they differentiated into mature adipocytes in vivo 3 weeks after transplantation. In contrast, allogenic control preadipocytes, which can differentiate in vitro, did not differentiate in vivo. These results indicate that donor progenitor cells can differentiate in cloned animal.

  14. Cell transplantation to the auditory nerve and cochlear duct.

    PubMed

    Sekiya, Tetsuji; Kojima, Ken; Matsumoto, Masahiro; Kim, Tae-Soo; Tamura, Tetsuya; Ito, Juichi

    2006-03-01

    We have developed a technique to deliver cells to the inner ear without injuring the membranes that seal the endolymphatic and perilymphatic chambers. The integrity of these membranes is essential for normal hearing, and the technique should significantly reduce surgical trauma during cell transplantation. Embryonic stem cells transplanted at the internal auditory meatal portion of an atrophic auditory nerve migrated extensively along it. Four-five weeks after transplantation, the cells were found not only throughout the auditory nerve, but also in Rosenthal's canal and the scala media, the most distal portion of the auditory nervous system where the hair cells reside. Migration of the transplanted cells was more extensive following damage to the auditory nerve. In the undamaged nerve, migration was more limited, but the cells showed more signs of neuronal differentiation. This highlights an important balance between tissue damage and the potential for repair.

  15. Tuberculosis in Hematopoietic Stem Cell Transplant Recipients

    PubMed Central

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

    2013-01-01

    Literature on tuberculosis (TB) occurring in recipients of Hematopoietic Stem Cell Transplant (HSCT) is scanty even in countries where TB is common. Most reports of TB in HSCT patients were from ASIA, in fact the TB incidence ranging from 0.0014 (USA) to 16% (Pakistan). There are few reports of TB diagnosis during the first two weeks after HSCT; most of cases described in the literature occurred after 90 days of HSCT, and the lung was the organ most involved. The mortality ranged from 0 to 50% and is higher in allogeneic HSCT than in autologous. There is no consensus regarding the screening with tuberculin skin test or QuantiFERON-TB gold, primary prophylaxis for latent TB, and whether the epidemiologic query should be emphasized in developing countries with high prevalence of TB. PMID:24363876

  16. Treatment of patients with secondary central nervous system lymphoma with high-dose busulfan/thiotepa-based conditioning and autologous stem cell transplant.

    PubMed

    Oh, Danielle H; Chua, Neil; Street, Lesley; Stewart, Douglas A

    2016-01-01

    Although the survival rates are extremely low for patients with secondary central nervous system lymphoma (SCNSL) treated with conventional chemotherapy and radiotherapy, more encouraging outcomes have recently been reported in small series with high-dose (HD) therapy and autologous stem cell transplant (ASCT). The optimal HD regimen for SCNSL is unknown. Despite reports of thiotepa/busulfan-based conditioning for primary CNS lymphoma, very little data exist regarding the use of this regimen for SCNSL. We analyzed 23 patients with SCNSL (median age 62 years) who underwent ASCT at two Alberta centers using thiotepa, busulfan, cyclophosphamide (TBC) in six patients prior to 2011 and rituximab-busulfan, melphalan, thiotepa (R-BuMelTt) in 17 patients after 2011. At a median follow-up of 27.8 months (4.2-113.6), the 2-year actuarial rate of progression-free survival was 76.1%. In conclusion, our results demonstrate encouraging survival outcomes for patients with SCNSL treated with R-BuMelTt and ASCT.

  17. Intensive care outcomes in adult hematopoietic stem cell transplantation patients.

    PubMed

    Bayraktar, Ulas D; Nates, Joseph L

    2016-02-10

    Although outcomes of intensive care for patients undergoing hematopoietic stem cell transplantation (HSCT) have improved in the last two decades, the short-term mortality still remains above 50% among allogeneic HSCT patients. Better selection of HSCT patients for intensive care, and consequently reduction of non-beneficial care, may reduce financial costs and alleviate patient suffering. We reviewed the studies on intensive care outcomes of patients undergoing HSCT published since 2000. The risk factors for intensive care unit (ICU) admission identified in this report were primarily patient and transplant related: HSCT type (autologous vs allogeneic), conditioning intensity, HLA mismatch, and graft-versus-host disease (GVHD). At the same time, most of the factors associated with ICU outcomes reported were related to the patients' functional status upon development of critical illness and interventions in ICU. Among the many possible interventions, the initiation of mechanical ventilation was the most consistently reported factor affecting ICU survival. As a consequence, our current ability to assess the benefit or futility of intensive care is limited. Until better ICU or hospital mortality prediction models are available, based on the available evidence, we recommend practitioners to base their ICU admission decisions on: Patient pre-transplant comorbidities, underlying disease status, GVHD diagnosis/grade, and patients' functional status at the time of critical illness.

  18. Patients with mantle-cell lymphoma relapsing after autologous stem cell transplantation may be rescued by allogeneic transplantation.

    PubMed

    Martínez, C; Carreras, E; Rovira, M; Urbano-Ispizua, A; Esteve, J; Perales, M; Fernández, F; Montserrat, E

    2000-09-01

    Two patients with disseminated mantle-cell lymphoma relapsed 24 and 13 months, respectively, after high-dose chemotherapy and autologous stem cell transplantation (autoSCT). Both patients had an HLA-identical sibling and received an allogeneic stem cell transplant (alloSCT) 32 and 18 months after autologous transplant, after conditioning with fractionated 12 Gy total body irradiation plus cyclophosphamide 120 mg/kg. They are both alive and in complete remission 24 months after transplant. Both patients have developed chronic graft-versus-host disease and their Karnofsky performance status is 90%. AlloSCT may offer a useful approach in a subgroup of patients with mantle-cell lymphoma who have relapsed after autologous transplantation.

  19. Hematopoietic cell transplantation for mucopolysaccharidosis IIB (Hunter syndrome).

    PubMed

    Peters, C; Krivit, W

    2000-05-01

    Hunter syndrome is an X-linked metabolic storage disorder arising from deficiency of iduronate sulfatase enzyme activity. Despite the successful use of hematopoietic cell transplantation for a variety of lysosomal and peroxisomal storage diseases, limited benefit occurs following transplantation in either the severe or mild forms of Hunter syndrome. A brief ethical commentary is provided on the case of a boy with mucopolysaccharidosis IIB (ie the mild form) who received an unrelated umbilical cord blood transplant to improve his future quality of life. Bone Marrow Transplantation (2000).

  20. Chromaffin cell transplants: from the lab to the clinic.

    PubMed

    Ambriz-Tututi, Mónica; Monjaraz-Fuentes, Fernanda; Drucker-Colín, René

    2012-12-17

    Chromaffin cell transplants have been explored since the early 1980s as a promising alternative in different pathological states, mainly Parkinson's disease and chronic pain. Advances are significant since transplants have been performed in humans. The general mechanism of these transplants relies in the capacity of chromaffin cells to act as mini-pumps that release amines and peptides. Different strategies are being used to improve the efficacy of transplants. However, a remaining hurdle is to determine the viability across time and the interaction with the microenvironment of the graft. We analyzed previous and current results finding that although there is a lot of positive evidence, there is also a lack of molecular studies that support behavioral results. The present review gives an update on recent advances of chromaffin cell transplants and their future in the clinic.

  1. [Treatment of relapsed Hodgkin lymphoma after autologous stem cell transplantation].

    PubMed

    Illés, Árpád; Simon, Zsófia; Udvardy, Miklós; Magyari, Ferenc; Jóna, Ádám; Miltényi, Zsófia

    2017-08-01

    Approximately 10-30% of Hodgkin lymphoma patients relapses or experience refractory disease after first line treatment. Nowadays, autologous stem cell transplantation can successfully salvage half of these patients, median overall survival is only 2-2.5 years. Several prognostic factors determine success of autologous stem cell transplantation. Result of transplantation can be improved considering these factors and using consolidation treatment, if necessary. Patients who relapse after autologous transplantation had worse prognosis, treatment of this patient population is unmet clinical need. Several new treatment options became available in the recent years (brentuximab vedotin and immuncheckpoint inhibitors). These new treatment options offer more chance for cure in relapsed/refractory Hodgkin patients. Outcome of allogenic stem cell transplantation can be improved by using haploidentical donors. New therapeutic options will be discussed in this review. Orv Hetil. 2017; 158(34): 1338-1345.

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

    PubMed

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

    2013-05-01

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

  3. Human adipose-derived stem cells promote vascularization of collagen-based scaffolds transplanted into nude mice

    PubMed Central

    Cherubino, Mario; Valdatta, Luigi; Balzaretti, Riccardo; Pellegatta, Igor; Rossi, Federica; Protasoni, Marina; Tedeschi, Alessandra; Accolla, Roberto S; Bernardini, Giovanni; Gornati, Rosalba

    2016-01-01

    Aim: After in vivo implantation of cell-loaded devices, only the cells close to the capillaries can obtain nutrients to maintain their functions. It is known that factors secreted by stem cells, rather than stem cells themselves, are fundamental to guarantee new vascularization in the area of implant. Materials & methods: To investigate this possibility, we have grafted mice with Bilayer and Flowable Integra® scaffolds, loaded or not with human adipose-derived stem cells. Results: Our results support the therapeutic potential of human adipose-derived stem cells to induce new vascular networks of engineered organs and tissues. Conclusion: This finding suggests that our approach can help to form new vascular networks that allow sufficient vascularization of engineered organs and tissues in cases of difficult wound healing due to ischemic conditions. PMID:26965659

  4. Essential role for B cells in transplantation tolerance

    PubMed Central

    Redfield, Robert R; Rodriguez, Eduardo; Parsons, Ronald; Vivek, Kumar; Mustafa, Moiz M; Noorchashm, Hooman; Naji, Ali

    2017-01-01

    T lymphocytes are the primary targets of immunotherapy in clinical transplantation. However, B lymphocytes are detrimental to graft survival by virtue of their capacity to present antigen to T cells via the indirect pathway of allorecognition and the generation of donor specific alloantibody. Furthermore, the long-term survival of organ allografts remains challenged by chronic rejection, a process in which activated B cells have been found to play a significant role. Therefore, the achievement of transplantation tolerance will likely require induction of both T and B cell tolerance to alloantigens. Moreover, human and animal investigations have shown that subsets of B cells, Transitional and Regulatory, are inherently tolerogenic. Developing therapeutic strategies that exploit these populations may be key to achieving transplantation tolerance. In this review we describe the current evidence for the essential role of B cells in transplant tolerance and discuss emerging B cell directed strategies to achieve allograft tolerance. PMID:21982511

  5. Imaging of complications from hematopoietic stem cell transplant

    PubMed Central

    Pandey, Tarun; Maximin, Suresh; Bhargava, Puneet

    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 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

  6. First Successful Haploidentical Stem Cell Transplantation in Romania.

    PubMed

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

    2016-09-01

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

  7. Population Pharmacokinetics and Optimal Sampling Strategy for Model-Based Precision Dosing of Melphalan in Patients Undergoing Hematopoietic Stem Cell Transplantation.

    PubMed

    Mizuno, Kana; Dong, Min; Fukuda, Tsuyoshi; Chandra, Sharat; Mehta, Parinda A; McConnell, Scott; Anaissie, Elias J; Vinks, Alexander A

    2017-09-16

    High-dose melphalan is an important component of conditioning regimens for patients undergoing hematopoietic stem cell transplantation. The current dosing strategy based on body surface area results in a high incidence of oral mucositis and gastrointestinal and liver toxicity. Pharmacokinetically guided dosing will individualize exposure and help minimize overexposure-related toxicity. The purpose of this study was to develop a population pharmacokinetic model and optimal sampling strategy. A population pharmacokinetic model was developed with NONMEM using 98 observations collected from 15 adult patients given the standard dose of 140 or 200 mg/m(2) by intravenous infusion. The determinant-optimal sampling strategy was explored with PopED software. Individual area under the curve estimates were generated by Bayesian estimation using full and the proposed sparse sampling data. The predictive performance of the optimal sampling strategy was evaluated based on bias and precision estimates. The feasibility of the optimal sampling strategy was tested using pharmacokinetic data from five pediatric patients. A two-compartment model best described the data. The final model included body weight and creatinine clearance as predictors of clearance. The determinant-optimal sampling strategies (and windows) were identified at 0.08 (0.08-0.19), 0.61 (0.33-0.90), 2.0 (1.3-2.7), and 4.0 (3.6-4.0) h post-infusion. An excellent correlation was observed between area under the curve estimates obtained with the full and the proposed four-sample strategy (R (2) = 0.98; p < 0.01) with a mean bias of -2.2% and precision of 9.4%. A similar relationship was observed in children (R (2) = 0.99; p < 0.01). The developed pharmacokinetic model-based sparse sampling strategy promises to achieve the target area under the curve as part of precision dosing.

  8. Cell transplantation therapy for diabetes mellitus: endocrine pancreas and adipocyte.

    PubMed

    Fujikura, Junji; Hosoda, Kiminori; Nakao, Kazuwa

    2013-01-01

    Experimental transplantation of endocrine tissues has led to significant advances in our understanding of endocrinology and metabolism. Endocrine cell transplantation therapy is expected to be applied to the treatment of metabolic endocriopathies. Restoration of functional pancreatic beta-cell mass or of functional adipose mass are reasonable treatment approaches for patients with diabetes or lipodystrophy, respectively. Human induced pluripotent stem (iPS) cell research is having a great impact on life sciences. Doctors Takahashi and Yamanaka discovered that the forced expression of a set of genes can convert mouse and human somatic cells into a pluripotent state [1, 2]. These iPS cells can differentiate into a variety of cell types. Therefore, iPS cells from patients may be a potential cell source for autologous cell replacement therapy. This review briefly summarizes the current knowledge about transplantation therapy for diabetes mellitus, the development of the endocrine pancreas and adipocytes, and endocrine-metabolic disease-specific iPS cells.

  9. Factors associated with hematopoietic cell transplantation (HCT) among patients in a population-based study of myelodysplastic syndrome (MDS) in Minnesota.

    PubMed

    Smith, Angela R; Warlick, Erica D; Roesler, Michelle A; Poynter, Jenny N; Richardson, Michaela; Nguyen, Phuong; Cioc, Adina; Hirsch, Betsy; Ross, Julie A

    2015-10-01

    Myelodysplastic syndrome (MDS) is a clonal hematopoietic stem cell disorder characterized by dysplastic changes in the bone marrow, ineffective erythropoiesis, and an increased risk of developing acute myeloid leukemia. Treatment planning for patients with MDS is a complex process, and we sought to better characterize hematopoietic cell transplantation (HCT) outcomes and the factors that play into decision-making regarding referral of adults with MDS for definitive therapy with HCT. Patients enrolled in a population-based study of MDS between April 2010 and January 2013 who underwent HCT within the first year after enrollment were included in this analysis. Age- and risk-matched MDS patient controls also enrolled during that time period were used as a comparison. Survival was significantly better in the HCT group (48 vs. 21 %, log-rank p value 0.009). Non-HCT patients were more likely to have comorbidities, and HCT patients were more likely to have a college degree and an income >$80,000. All three of these variables were independently associated with HCT, but none impacted survival. Patients with MDS in our study who underwent HCT had better survival than a comparable group of patients who did not undergo HCT. With refined treatment techniques, more patients may be able to be considered for this therapy. More work needs to be done to determine why education and income appear to impact the decision to pursue HCT, but these factors may impact referral to an academic center where aggressive therapy like HCT is more likely to be considered.

  10. Secondary solid cancer screening following hematopoietic cell transplantation

    PubMed Central

    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

  11. Secondary solid cancer screening following hematopoietic cell transplantation.

    PubMed

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

    2015-08-01

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

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

    PubMed Central

    Chan, Jerry K. Y.; Götherström, Cecilia

    2014-01-01

    Osteogenesis imperfecta (OI) can be a severe disorder that can be diagnosed before birth. Transplantation of mesenchymal stem cells (MSC) has the potential to improve the bone structure, growth, and fracture healing. In this review, we give an introduction to OI and MSC, and the basis for pre- and postnatal transplantation in OI. We also summarize the two patients with OI who have received pre- and postnatal transplantation of MSC. The findings suggest that prenatal transplantation of allogeneic MSC in OI is safe. The cell therapy is of likely clinical benefit with improved linear growth, mobility, and reduced fracture incidence. Unfortunately, the effect is transient. For this reason, postnatal booster infusions using same-donor MSC have been performed with clinical benefit, and without any adverse events. So far there is limited experience in this specific field and proper studies are required to accurately conclude on clinical benefits of MSC transplantation to treat OI. PMID:25346689

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

    PubMed

    Claude Gorin, Norbert

    2016-04-01

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

  14. A Calpain Inhibitor Enhances the Survival of Schwann Cells In Vitro and after Transplantation into the Injured Spinal Cord

    PubMed Central

    Guller, Yelena; Raffa, Scott J.; Hurtado, Andres; Bunge, Mary Bartlett

    2010-01-01

    Abstract Despite the diversity of cells available for transplantation into sites of spinal cord injury (SCI), and the known ability of transplanted cells to integrate into host tissue, functional improvement associated with cellular transplantation has been limited. One factor potentially limiting the efficacy of transplanted cells is poor cell survival. Recently we demonstrated rapid and early death of Schwann cells (SCs) within the first 24 h after transplantation, by both necrosis and apoptosis, which results in fewer than 20% of the cells surviving beyond 1 week. To enhance SC transplant survival, in vitro and in vivo models to rapidly screen compounds for their ability to promote SC survival are needed. The current study utilized in vitro models of apoptosis and necrosis, and based on withdrawal of serum and mitogens and the application of hydrogen peroxide, we screened several inhibitors of apoptosis and necrosis. Of the compounds tested, the calpain inhibitor MDL28170 enhanced SC survival both in vitro in response to oxidative stress induced by application of H2O2, and in vivo following delayed transplantation into the moderately contused spinal cord. The results support the use of calpain inhibitors as a promising new treatment for promoting the survival of transplanted cells. They also suggest that in vitro assays for cell survival may be useful for establishing new compounds that can then be tested in vivo for their ability to promote transplanted SC survival. PMID:20568964

  15. Hemophagocytic syndrome following haploidentical peripheral blood stem cell transplantation with post-transplant cyclophosphamide.

    PubMed

    Jaiswal, Sarita Rani; Chakrabarti, Aditi; Chatterjee, Sumita; Bhargava, Sneh; Ray, Kunal; Chakrabarti, Suparno

    2016-02-01

    Hemophagocytic syndrome (HPS) is a rare but serious complication after allogeneic transplantation which has been reported to be particularly high after unrelated cord blood transplantation. We report on the incidence, risk factors and outcome of HPS in 51 patients (age 2-64 years) after haploidentical peripheral blood stem cell (PBSC) transplantation with post-transplantation cyclophosphamide (PTCY). The incidence of HPS was 12.2 %, occurring at a median of 18 days. The non-relapse mortality in patients with HPS was 83.3 % compared to 11.6 % in patients without HPS. Complete donor chimerism was documented in all patients with HPS. Definite infective etiology was identified in two patients only. The others were refractory to multiple lines of treatment and 3 patients underwent a second transplant. Even though the symptoms and biochemical markers of HPS showed prompt response in 2/3 patients undergoing a second allograft, they succumbed to infections before haematological recovery. The others succumbed to multi-organ failure or infections. Age < 10 years, transplantation for non-malignant disease and high CD34 content of the graft were identified as risk factors for HPS. Considering the fact that post-transplant HPS is usually a refractory and fatal condition, we discuss further attempts at deciphering the pathogenesis, developing modalities to prevent this complication and improve the outcome.

  16. Tailored strategy for AML patients receiving allogeneic peripheral blood stem cell transplantation.

    PubMed

    Sohn, Sang Kyun; Kim, Jong Gwang; Kim, Dong Hwan

    2006-10-01

    Considering the heterogeneity of acute myelogenous leukemia (AML), along with the pros and cons of allogeneic peripheral blood stem cell transplantation (PBSCT), a tailored strategy is needed to minimize the transplant-related mortality and maximize the transplant outcomes in AML patients exhibiting certain factors that have an impact on the post-transplant quality of life and outcomes. The factors that need to be considered when tailoring a strategy in an allogeneic PBSCT setting include the recipient's performance status and co-morbid disease include AML risk stratification, disease status, expected severity of graft-versus-host disease, and the necessity of a graft-versus-leukemia effect. Accordingly, this review article describes a possible tailoring strategy for AML patients receiving allogeneic PBSCT based on certain factors influencing the transplant outcome.

  17. [Pegfilgrastim in hematopoietic stem cell transplantation].

    PubMed

    Fernández Alvarez, R

    2010-12-01

    Pegylation implies progress in filgrastim therapy. The addition of one molecule of polyethylene glycol (PEG) increases the drug's half-life by reducing renal excretion. A single dose of pegfilgrastim is equivalent to a daily administration of G-CSF for recovering from neutropenia after cancer chemotherapy. Pegfilgrastim is also useful to mobilize hematopoietic stem cells. Several studies have researched its efficacy in this context, in patients with myeloma or lymphoma. Outcomes suggest that it has an efficacy similar to daily G-CSF. In allogeneic donors, a single 12-mg dose of pegfilgrastim produces sufficient increase of CD34+ in peripheral blood, with acceptable toxicity. There is interest on the data about the various functional and biologic properties of hematopoietic stem cells mobilized with pegfilgrastim compared to G-CSF, and on the effect that these differences may have on the graft composition. The administration of a single dose of pegfilgrastim after autologous transplantation has been shown to shorten the time for leukocyte recovery in a manner similar to G-CSF

  18. Stem Cell Transplantation for Pulpal Regeneration: A Systematic Review

    PubMed Central

    Jakusz, Kimberley; Jochens, Arne; Dörfer, Christof; Schwendicke, Falk

    2015-01-01

    For treating pulpal pathological conditions, pulpal regeneration through transplanted stem/progenitor cells might be an alternative to conventional root canal treatment. A number of animal studies demonstrated beneficial effects of stem/progenitor cell transplantation for pulp–dentin complex regeneration, that is, pulpal tissue, neural, vascular, and dentinal regeneration. We systematically reviewed animal studies investigating stem/progenitor cell-mediated pulp–dentin complex regeneration. Studies quantitatively comparing pulp–dentin complex regeneration after transplantation of stem/progenitor cells versus no stem/progenitor cell transplantation controls in intraoral in vivo teeth animal models were analyzed. The following outcomes were investigated: regenerated pulp area per root canal total area, capillaries per total surface, regenerated dentinal area per total defect area, and nerves per total surface. PubMed and EMBASE were screened for studies published until July 2014. Cross-referencing and hand searching were used to identify further articles. Standardized mean differences (SMD) and 95% confidence intervals (95% CI) were calculated using random-effects meta-analysis. To assess possible bias, SYRCLE's risk of bias tool for animal studies was used. From 1364 screened articles, five studies (representing 64 animals) were included in the quantitative analysis. Risk of bias of all studies was high. Stem/progenitor cell-transplanted pulps showed significantly larger regenerated pulp area per root canal total area (SMD [95% CI]: 2.28 [0.35–4.21]) and regenerated dentin area per root canal total area (SMD: 6.91 [5.39–8.43]) compared with no stem/progenitor cell transplantation controls. Only one study reported on capillaries per or nerves per total surface and found both significantly increased in stem/progenitor cell-transplanted pulps compared with controls. Stem/progenitor cell transplantation seems to enhance pulp–dentin complex regeneration in

  19. Patient housing barriers to hematopoietic cell transplantation: results from a mixed-methods study of transplant center social workers

    PubMed Central

    Mau, Lih-Wen; Majhail, Navneet S.; Bevans, Margaret; Clancy, Emilie; Messner, Carolyn; Parran, Leslie; Pederson, Kate A.; Ferguson, Stacy Stickney; Walters, Kent; Murphy, Elizabeth A.; Denzen, Ellen M.

    2015-01-01

    Purpose Hematopoietic cell transplantation (HCT) is performed in select centers in the United States (U.S.), and patients are often required to temporarily relocate to receive care. The purpose of this study was to identify housing barriers impacting access to HCT and potential solutions. Methods A mixed-methods primary study of HCT social workers was conducted to learn about patient housing challenges and solutions in place that help address those barriers. Three telephone focus groups were conducted with adult and pediatric transplant social workers (n=15). Focus group results informed the design of a national survey. The online survey was e-mailed to a primary social worker contact at 133 adult and pediatric transplant centers in the U.S. Transplant centers were classified based on the patient population cared for by the social worker. Results The survey response rate was 49 %. Among adult programs (n=45), 93 % of centers had patients that had to relocate closer to the transplant center to proceed with HCT. The most common type of housing option offered was discounted hotel rates. Among pediatric programs (n=20), 90 % of centers had patients that had to relocate closer to the transplant center to proceed with HCT. Ronald McDonald House was the most common option available. Conclusions This study is the first to explore housing challenges faced by patients undergoing HCT in the U.S. from the perspective of social workers and to highlight solutions that centers use. Transplant centers will benefit from this knowledge by learning about options for addressing housing barriers for their patients. PMID:26275767

  20. Hematopoietic cell transplantation in fetal lambs with ceroid-lipofuscinosis.

    PubMed

    Westlake, V J; Jolly, R D; Jones, B R; Mellor, D J; Machon, R; Zanjani, E D; Krivit, W

    1995-06-05

    Hematopoietic cells from the liver of normal 45-48-day-old fetal lambs (Hb type AA) were transplanted intraperitoneally into 58-60-day-old recipient fetuses (Hb type BB). The recipient fetuses resulted from mating homozygous ceroid-lipofuscinosis affected males with heterozygous, phenotypically normal, females. The sex of the donor fetus was also recorded. At age 2 1/2 months the recipient lambs with ceroid-lipofuscinosis were diagnosed by histopathology of brain biopsies. Monitoring of blood and bone marrow cells showed that an average of 9% of blood cells in ceroid-lipofuscinosis affected recipients were of donor origin. No differences were evident in the clinical course of disease, brain weight, or histopathology of organs between transplanted and non-transplanted lambs with ceroid-lipofuscinosis. Under the conditions of this experiment, transplantation of fetal hematopoietic cells was not beneficial.

  1. Autologous hematopoietic stem cell transplantation in progressive severe multiple sclerosis.

    PubMed

    Pandit, Awadh Kishor; Prasad, Kameshwar; Seth, Tulika

    2015-01-01

    Multiple sclerosis (MS) is a chronic inflammatory disease of central nervous system (CNS), which is disabling and majorly involves younger population. Various available treatments in forms of immunomodulation are not very effective; however, stem cell transplantation seems to be promising in recent literature. The current case report is a novel evidence for autologous hematopoietic stem cell transplantation (HSCT) in progressive MS. A 33 year old male with secondary progressive MS (SPMS), after being failed and/or intolerance to standard approved interferon (IFN) and mitoxantrone therapy, autologous HSCT was administered. At 2years of post-stem cell transplantation follow-up, he has remained stable with some improvement in functional status (Expanded Disability Status Scale (EDSS) reduced by 1.5), with no relapse, no treatment related complications, and no fresh magnetic resonance imaging (MRI) lesions. Autologous stem cell transplantation may be beneficial in progressive forms of MS, but needs to be tested in well-designed randomized trial.

  2. Isolation and transplantation of sturgeon early-stage germ cells.

    PubMed

    Pšenička, Martin; Saito, Taiju; Linhartová, Zuzana; Gazo, Ievgeniia

    2015-04-01

    We report, for the first time, a series of baseline techniques comprising isolation and transplantation of female and male early-stage germ cells in sturgeon to generate a germline chimera as a potential tool for surrogate reproduction and gene banking. Cells were dissociated from testis, characterized by mostly spermatogonia, and from ovary, exclusively comprising oogonia and previtellogenic oocytes, of Acipenser baerii, using 0.3% trypsin (2 hours, 23 °C) dissolved in PBS, isotonic with blood plasma. The dissociated germ cells were sorted by Percoll gradient centrifugation followed by immunolabeling with germ cell-specific vasa antibody DDX4, while 10% to 30% Percoll solution contained 79.4% and 70.8% labeled testicular and ovarian cells. Sorted germ cells were transplanted into a cavity close to a presumptive genital ridge of newly hatched heterospecific Acipenser ruthenus larvae with fluorescein isothiocyanate-labeled endogenous primordial germ cells. The transplanted germ cells were randomly distributed in the body cavity through 30-day posttransplantation (dpt). Subsequently, the cells were organized into genital ridges 50 dpt and proliferated 90 dpt. The number of both transplanted and endogenous germ cells significantly increased from 18.1, 22.2, and 29.1 (30 dpt) to 108.5, 90.8, and 118.5 (90 dpt) in ovarian, testicular, and endogenous germ cells, respectively (P < 0.05). The efficiency of transplantation was 60% (counted 90 dpt). Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Chemokine Receptor Signatures in Allogeneic Stem Cell Transplantation

    DTIC Science & Technology

    2015-08-01

    is a potentially effective strategy to reduce graft-versus-host disease (GVHD) after allogeneic HSCT without compromising the graft-versus- leukemia ...Porter DL (2015). “Reduced-intensity conditioning for allogeneic hematopoietic stem-cell transplantation in adults with acute myeloid leukemia .” Bone...Tallman MS, Wirk B, Bunjes DW, Devine SM, de Lima M, Weisdorf DJ, Uy GL (2015). “Allogeneic Hematopoietic Cell Transplant for Acute Myeloid Leukemia

  4. Acute Fibrinous and Organizing Pneumonia Following Hematopoietic Stem Cell Transplantation

    PubMed Central

    Lee, Sang Min; Park, Jae-Jung; Sung, Sun Hee; Kim, Yookyung; Lee, Kyoung Eun; Lee, Soon Nam; Seong, Chu Myong

    2009-01-01

    A 60-year-old man presented with cough, sputum, and dyspnea. He had a history of acute myeloid leukemia and hematopoietic stem cell transplantation with chronic renal failure. Chest CT scans showed miliary nodules and patchy consolidations. Histological examination revealed numerous fibrin balls within the alveoli and thickening of the alveolar septum, both of which are typical pathological features of acute fibrinous and organizing pneumonia (AFOP). We report the first case of AFOP following allogeneic hematopoietic stem cell transplantation. PMID:19543497

  5. Immunological considerations in in utero hematopoetic stem cell transplantation (IUHCT)

    PubMed Central

    Loewendorf, Andrea I.; Csete, Marie; Flake, Alan

    2014-01-01

    In utero hematopoietic stem cell transplantation (IUHCT) is an attractive approach and a potentially curative surgery for several congenital hematopoietic diseases. In practice, this application has succeeded only in the context of Severe Combined Immunodeficiency Disorders. Here, we review potential immunological hurdles for the long-term establishment of chimerism and discuss relevant models and findings from both postnatal hematopoietic stem cell transplantation and IUHCT. PMID:25610396

  6. Allogeneic haematopoietic stem cell transplantation for mitochondrial neurogastrointestinal encephalomyopathy.

    PubMed

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

    2015-10-01

    Haematopoietic stem cell transplantation has been proposed as treatment for mitochondrial neurogastrointestinal encephalomyopathy, a rare fatal autosomal recessive disease due to TYMP mutations that result in thymidine phosphorylase deficiency. We conducted a retrospective analysis of all known patients suffering from mitochondrial neurogastrointestinal encephalomyopathy who underwent allogeneic haematopoietic stem cell transplantation between 2005 and 2011. Twenty-four patients, 11 males and 13 females, median age 25 years (range 10-41 years) treated with haematopoietic stem cell transplantation from related (n = 9) or unrelated donors (n = 15) in 15 institutions worldwide were analysed for outcome and its associated factors. Overall, 9 of 24 patients (37.5%) were alive at last follow-up with a median follow-up of these surviving patients of 1430 days. Deaths were attributed to transplant in nine (including two after a second transplant due to graft failure), and to mitochondrial neurogastrointestinal encephalomyopathy in six patients. Thymidine phosphorylase activity rose from undetectable to normal levels (median 697 nmol/h/mg protein, range 262-1285) in all survivors. Seven patients (29%) who were engrafted and living more than 2 years after transplantation, showed improvement of body mass index, gastrointestinal manifestations, and peripheral neuropathy. Univariate statistical analysis demonstrated that survival was associated with two defined pre-transplant characteristics: human leukocyte antigen match (10/10 versus <10/10) and disease characteristics (liver disease, history of gastrointestinal pseudo-obstruction or both). Allogeneic haematopoietic stem cell transplantation can restore thymidine phosphorylase enzyme function in patients with mitochondrial neurogastrointestinal encephalomyopathy and improve clinical manifestations of mitochondrial neurogastrointestinal encephalomyopathy in the long term. Allogeneic haematopoietic stem cell transplantation

  7. Allogeneic haematopoietic stem cell transplantation for mitochondrial neurogastrointestinal encephalomyopathy

    PubMed Central

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

    2015-01-01

    Haematopoietic stem cell transplantation has been proposed as treatment for mitochondrial neurogastrointestinal encephalomyopathy, a rare fatal autosomal recessive disease due to TYMP mutations that result in thymidine phosphorylase deficiency. We conducted a retrospective analysis of all known patients suffering from mitochondrial neurogastrointestinal encephalomyopathy who underwent allogeneic haematopoietic stem cell transplantation between 2005 and 2011. Twenty-four patients, 11 males and 13 females, median age 25 years (range 10–41 years) treated with haematopoietic stem cell transplantation from related (n = 9) or unrelated donors (n = 15) in 15 institutions worldwide were analysed for outcome and its associated factors. Overall, 9 of 24 patients (37.5%) were alive at last follow-up with a median follow-up of these surviving patients of 1430 days. Deaths were attributed to transplant in nine (including two after a second transplant due to graft failure), and to mitochondrial neurogastrointestinal encephalomyopathy in six patients. Thymidine phosphorylase activity rose from undetectable to normal levels (median 697 nmol/h/mg protein, range 262–1285) in all survivors. Seven patients (29%) who were engrafted and living more than 2 years after transplantation, showed improvement of body mass index, gastrointestinal manifestations, and peripheral neuropathy. Univariate statistical analysis demonstrated that survival was associated with two defined pre-transplant characteristics: human leukocyte antigen match (10/10 versus <10/10) and disease characteristics (liver disease, history of gastrointestinal pseudo-obstruction or both). Allogeneic haematopoietic stem cell transplantation can restore thymidine phosphorylase enzyme function in patients with mitochondrial neurogastrointestinal encephalomyopathy and improve clinical manifestations of mitochondrial neurogastrointestinal encephalomyopathy in the long term. Allogeneic haematopoietic stem cell transplantation

  8. Liver cell therapy and tissue engineering for transplantation.

    PubMed

    Vacanti, Joseph P; Kulig, Katherine M

    2014-06-01

    Liver transplantation remains the only definitive treatment for liver failure and is available to only a tiny fraction of patients with end-stage liver diseases. Major limitations for the procedure include donor organ shortage, high cost, high level of required expertise, and long-term consequences of immune suppression. Alternative cell-based liver therapies could potentially greatly expand the number of patients provided with effective treatment. Investigative research into augmenting or replacing liver function extends into three general strategies. Bioartificial livers (BALs) are extracorporeal devices that utilize cartridges of primary hepatocytes or cell lines to process patient plasma. Injection of liver cell suspensions aims to foster organ regeneration or provide a missing metabolic function arising from a genetic defect. Tissue engineering recreates the organ in vitro for subsequent implantation to augment or replace patient liver function. Translational models and clinical trials have highlighted both the immense challenges involved and some striking examples of success.

  9. Macroporous thin membranes for cell transplant in regenerative medicine.

    PubMed

    Antolinos-Turpín, C M; Morales Román, R M; Rodenas-Rochina, J; Gómez Ribelles, J L; Gómez-Tejedor, J A

    2015-10-01

    The aim of this paper is to present a method to produce macroporous thin membranes made of poly (ethyl acrylate-co-hydroxyethyl acrylate) copolymer network with varying cross-linking density for cell transplantation and prosthesis fabrication. The manufacture process is based on template techniques and anisotropic pore collapse. Pore collapse was produced by swelling the membrane in acetone and subsequently drying and changing the solvent by water to produce 100 microns thick porous membranes. These very thin membranes are porous enough to hold cells to be transplanted to the organism or to be colonized by ingrowth from neighboring tissues in the organism, and they present sufficient tearing stress to be sutured with surgical thread. The obtained pore morphology was observed by Scanning Electron Microscope, and confocal laser microscopy. Mechanical properties were characterized by stress-strain experiments in tension and tearing strength measurements. Morphology and mechanical properties were related to the different initial thickness of the scaffold and the cross-linking density of the polymer network. Seeding efficiency and proliferation of mesenchymal stem cells inside the pore structure were determined at 2 h, 1, 7, 14 and 21 days from seeding. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. MHC universal cells survive in an allogeneic environment after incompatible transplantation.

    PubMed

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  12. Thoracoscopic cell sheet transplantation with a novel device.

    PubMed

    Maeda, Masanori; Yamato, Masayuki; Kanzaki, Masato; Iseki, Hiroshi; Okano, Teruo

    2009-06-01

    Regenerative medicine with transplantable cell sheets fabricated on temperature-responsive culture surfaces has been successfully achieved in clinical applications, including skin and cornea treatment. Previously, we reported that transplantation of fibroblast cell sheets to wounded lung had big advantages for sealing intraoperative air leaks compared with conventional materials. Here, we report a novel device for minimally invasive transplantation of cell sheets in endoscopic surgery, such as video-assisted thoracoscopic surgery (VATS). The novel device was designed with a computer-aided design (CAD) system, and the three-dimensional (3D) data were transferred to a 3D printer. With this rapid prototyping system, the cell sheet transplantation device was fabricated using a commercially available photopolymer approved for clinical use. Square cell sheets (24 x 24 mm) were successfully transplanted onto wound sites of porcine lung placed in a human body model, with the device inserted through a 12 mm port. Such a device would enable less invasive transplantation of cell sheets onto a wide variety of internal organs.

  13. Results of hematopoietic stem cell transplant in Shiraz: 15 years experience in southern Iran.

    PubMed

    Ramzi, Mani; Nourani, Habib; Zakerinia, Maryam; Dehghani, Mehdi; Vojdani, Reza; Haghshenas, Mansour

    2010-03-01

    Over the past 2 decades, hematopoietic stem cell transplant has evolved from an experimental procedure to the standard of care, and it is integrated into the management of many diseases. Hematopoietic stem cell transplant was established at Shiraz University of Medical Sciences in 1993. Here, we describe 15 years experience with stem cell transplant at our center in southern Iran. We provide information on indication, donor type, conditioning chemotherapy regimen, outcome, survival, and long-term follow-up in our stem cell activity. From May 1993 to October 2008, 423 patients underwent allogeneic (n=311) and autologous (n=112) stem cell transplants at our center. For allogeneic stem cell transplant, the conditioning chemotherapy regimen comprised busulfan, cyclophosphamide, and antithymocyte globulin for thalassemic patients; busulfan and cyclophosphamide for leukemia patients; and cyclophosphamide and antithymocyte globulin for patients with aplastic anemia. During this period, 155 B-thalassemia major patients (mean age, 9.5 years; range, 2-20 years) underwent allogeneic marrow transplant. Of 155 patients with a diagnosis of thalassemia major, 112 are alive (72%) with full engraftment after a median follow-up of about 8.1 years (range, 12-184 months). During this time, 127 leukemia patients including acute myelogenous leukemia (n=68), acute lymphoblastic leukemia (n=30) and chronic myelogenous leukemia (n=29), received allogeneic stem cell transplant. In this group, long-term, disease-free survival (cure rate) was 67%, 60%, and 62%. These data reflect the important role of hematopoietic stem cell transplant in improving survival for a variety of hematopoietic system disorders at our center in Southern Iran. In patients with B-thalassemia major hematopoietic stem cell transplant seems to be the treatment of choice, because it leads to a cure in all classes (Lucarelli risk group, I-III). Based on high success rates in patients with class II and III thalassemia with

  14. Transplantation tool integrated with MEMS manipulator for retinal pigment epithelium cell sheet.

    PubMed

    Wada, H; Konishi, S

    2013-01-01

    This paper reports a transplantation tool for the retinal pigment epithelium in an eye. We have developed MEMS manipulator as an end-effector for transplantation of retinal pigment epithelium cell sheet. Typical size of MEMS manipulator is 3mm×3mm. MEMS manipulator was made of polydimethylsiloxane and driven by pneumatic balloon actuators. MEMS manipulator have been improved and integrated with several functions by sensors and actuators. MEMS manipulator is integrated into a transplantation tool. A whole tool also requires improvements based on our experimental results. We have improved our tool in terms of assembling, sealing, and operation.

  15. Hematopoietic stem cell transplantation for infantile osteopetrosis

    PubMed Central

    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

    2015-01-01

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

  16. Children's lived experiences of hematopoietic stem cell transplantation.

    PubMed

    Manookian, Arpi; Nasrabadi, Alireza Nikbakht; Asadi, Monireh

    2014-09-01

    Although hematopoietic stem cell transplantation is a valuable treatment in many life-threatening pediatric disorders, a large number of children who receive hematopoietic stem cell transplantation are faced with a variety of physical and psychological problems throughout this process. In this study, we explored the lived experiences of these children during their treatment to provide a better understanding of their main concerns, emotions, and expectations. The participants were six children, aged between 6 and 17 years, who underwent hematopoietic stem cell transplantation. Data were collected through individual, in-depth, and semistructured interviews. Using interpretive phenomenological analysis, the findings revealed that the children experienced "transplantation rejoicing" in this "difficult passage", which was associated with "deepening of family ties". Awareness of these experiences, feelings, and concerns can help in the development of more professional interventions to provide children with holistic care during their hospitalization.

  17. Combinatorial human progenitor cell transplantation optimizes islet regeneration through secretion of paracrine factors.

    PubMed

    Bell, Gillian I; Meschino, Michael T; Hughes-Large, Jennifer M; Broughton, Heather C; Xenocostas, Anargyros; Hess, David A

    2012-07-20

    Transplanted human bone marrow (BM) and umbilical cord blood (UCB) progenitor cells activate islet-regenerative or revascularization programs depending on the progenitor subtypes administered. Using purification of multiple progenitor subtypes based on a conserved stem cell function, high aldehyde dehydrogenase (ALDH) activity (ALDH(hi)), we have recently shown that transplantation of BM-derived ALDH(hi) progenitors improved systemic hyperglycemia and augmented insulin secretion by increasing islet-associated proliferation and vascularization, without increasing islet number. Conversely, transplantation of culture-expanded multipotent-stromal cells (MSCs) derived from BM ALDH(hi) cells augmented total beta cell mass via formation of beta cell clusters associated with the ductal epithelium, without sustained islet vascularization. To identify paracrine effectors produced by islet-regenerative MSCs, culture-expanded BM ALDH(hi) MSCs were transplanted into streptozotocin-treated nonobese diabetic/severe combine immune deficient (SCID) mice and segregated into islet-regenerative versus nonregenerative cohorts based on hyperglycemia reduction, and subsequently compared for differential production of mRNA and secreted proteins. Regenerative MSCs showed increased expression of matrix metalloproteases, epidermal growth factor receptor (EGFR)-activating ligands, and downstream effectors of Wnt signaling. Regenerative MSC supernatant also contained increased levels of pro-angiogenic versus pro-inflammatory cytokines, and augmented the expansion of ductal epithelial but not beta cells in vitro. Conversely, co-culture with UCB ALDH(hi) cells induced beta cell but not ductal epithelial cell proliferation. Sequential transplantation of MSCs followed by UCB ALDH(hi) cells improved hyperglycemia and glucose tolerance by increasing beta cell mass associated with the ductal epithelium and by augmenting intra-islet capillary densities. Thus, combinatorial human progenitor cell

  18. Dry eye after haematopoietic stem cell transplantation.

    PubMed

    Ogawa, Y; Okamoto, S; Wakui, M; Watanabe, R; Yamada, M; Yoshino, M; Ono, M; Yang, H Y; Mashima, Y; Oguchi, Y; Ikeda, Y; Tsubota, K

    1999-10-01

    To determine the incidence, natural course, and severity of dry eye occurring or worsening after haematopoietic stem cell transplantation (SCT). At a tertiary care hospital, 53 patients undergoing allogeneic or autologous SCT followed by at least 180 days of follow up were studied prospectively. Examination included grading of symptoms of dry eye, evaluation of ocular surface, tear break up time, and Schirmer tests with and without nasal stimulation. Meibomian gland secretion was also examined using a slit lamp while applying steady digital pressure. Of the 53 patients, 44 received allografts. Half of these patients (22) developed dry eye or their pre-existing dry eye worsened after SCT, while none of nine autograft recipients did. Onset of dry eye was 171 (SD 59) days after SCT. Two types of dry eye occurred. One (n=10) was severe with ocular surface findings resembling Sjögren's syndrome and reduction of reflex tearing soon after onset. A mild type (n=12) had unimpaired reflex tearing. Meibomian gland dysfunction (MGD) was more frequent and severe in patients with dry eye and chronic graft versus host disease (GVHD), and overall severity of dry eye was greater in patients with MGD and chronic GVHD. Dry eye after SCT occurred only in allograft recipients, and was not evident in autograft recipients. The severe form of dry eye had a tendency to develop rapidly. Further study on the prediction and treatment of severe dry eye after SCT is necessary.

  19. [Parenteral nutrition in hematopoietic stem cell transplantation].

    PubMed

    Gómez Alvarez, M E

    2004-01-01

    Haematopoietic stem cell transplantation (HSCT) is a sophisticated procedure used in the treatment of solid tumors, haematological diseases and autoimmune disorders, which were characterized by an extremely poor prognosis only a few years earlier. Thousands of patients receive high-dose chemotherapy and radiotherapy around the world every year in order to treat these diseases. Therapy can induce aggressive changes associated with multiple organ failure, which is usually reversible, that can lead to special nutritional and metabolic conditions. Artificial nutrition, total parenteral nutrition in particular, is provided to patients undergoing HSCT to help minimize nutritional consequences of both conditioning regimens (mucositis, malabsorption, etc.) as well as complications resulting from the procedure (graft versus host disease, venoocclusive disease of the liver). This study reviews published guidelines for the use of parenteral nutrition in HSCT and includes important aspects for nutritional support in children, including controversy on potential benefits of special nutrients (glutamine, antioxidants, etc.) and furthermore discusses future trends. This paper also addresses the pharmacists role and the necessity for multidisciplinary teams to develop specific protocols.

  20. DNA Methylation Dynamics in Blood after Hematopoietic Cell Transplant

    PubMed Central

    Rodriguez, Ramon M.; Suarez-Alvarez, Beatriz; Salvanés, Rubén; Muro, Manuel; Martínez-Camblor, Pablo; Colado, Enrique; Sánchez, Miguel Alcoceba; Díaz, Marcos González; Fernandez, Agustin F.; Fraga, Mario F.; Lopez-Larrea, Carlos

    2013-01-01

    Epigenetic deregulation is considered a common hallmark of cancer. Nevertheless, recent publications have demonstrated its association with a large array of human diseases. Here, we explore the DNA methylation dynamics in blood samples during hematopoietic cell transplant and how they are affected by pathophysiological events during transplant evolution. We analyzed global DNA methylation in a cohort of 47 patients with allogenic transplant up to 12 months post-transplant. Recipients stably maintained the donor’s global methylation levels after transplant. Nonetheless, global methylation is affected by chimerism status. Methylation analysis of promoters revealed that methylation in more than 200 genes is altered 1 month post-transplant when compared with non-pathological methylation levels in the donor. This number decreased by 6 months post-transplant. Finally, we analyzed methylation in IFN-γ, FASL, IL-10, and PRF1 and found association with the severity of the acute graft-versus-host disease. Our results provide strong evidence that methylation changes in blood are linked to underlying physiological events and demonstrate that DNA methylation analysis is a viable strategy for the study of transplantation and for development of biomarkers. PMID:23451113

  1. Cutaneous Squamous Cell Carcinomas in Organ Transplant Recipients

    PubMed Central

    Chockalingam, Ramya; Downing, Christopher; Tyring, Stephen K.

    2015-01-01

    Non-melanoma skin cancers represent a major cause of morbidity after organ transplantation. Squamous cell carcinomas (SCC) are the most common cutaneous malignancies seen in this population, with a 65–100 fold greater incidence in organ transplant recipients compared to the general population. In recent years, human papillomaviruses (HPV) of the beta genus have been implicated in the pathogenesis of post-transplant SCCs. The underlying mechanism of carcinogenesis has been attributed to the E6 and E7 proteins of HPV. Specific immunosuppressive medications, such as the calcineurin inhibitors and azathioprine, are associated with a higher incidence of post-transplant SCCs compared to other immunosuppressive agents. Compared to other immunosuppressives, mTOR inhibitors and mycophenolate mofetil have been associated with a decreased risk of developing post-transplant non-melanoma skin cancers. As a result, they may represent ideal immunosuppressive medications in organ transplant recipients. Treatment options for post-transplant SCCs include surgical excision, Mohs micrographic surgery, systemic retinoid therapy, adjunct topical therapy, electrodessication and curettage, and radiation therapy. This review will discuss the epidemiology, risk factors, and management options of post-transplant SCCs. In addition, the underlying mechanisms of beta-HPV mediated carcinogenesis will be discussed. PMID:26239556

  2. Retrospective analysis of fluoroquinolone prophylaxis in patients undergoing allogeneic hematopoietic stem cell transplantation.

    PubMed

    Simondsen, Katherine A; Reed, Michael P; Mably, Mary S; Zhang, Yang; Longo, Walter L

    2013-12-01

    Patients undergoing allogeneic hematopoietic stem cell transplant are at a high risk for infection-related mortality in the immediate post-transplantation phase. Prophylaxis with a fluoroquinolone is now recommended to reduce this risk with the stipulation that surveillance for increased fluoroquinolone resistance Clostridium difficile associated diarrhea be conducted. We conducted a retrospective chart review of 48 patients who underwent an allogeneic hematopoietic stem cell transplant and received a fluoroquinolone for prophylaxis and 48 patients who underwent an allogeneic hematopoietic stem cell transplant who did not receive a fluoroquinolone for prophylaxis. All patients received the same standard antifungal, antiviral and anti-pneumocystis prophylaxis. Patients receiving fluoroquinolone prophylaxis had a lower incidence of febrile neutropenia than those not receiving prophylaxis, though the difference was not found to be statistically significant (83% vs. 67%, p = 0.098). Similar non-significant improvements in the number of positive cultures recovered during an episode of febrile neutropenia and antimicrobial days were noted. No significant increase in fluoroquinolone resistance, Clostridium difficile associated diarrhea, or in methicillin resistant Staphylococcus aureus infections were noted. Our single institution experience with fluoroquinolone prophylaxis for allogeneic hematopoietic stem cell transplant patients supports continuation of this practice. Expansion to autologous hematopoietic stem cell transplant patients may be appropriate based on guideline recommendations and our institution-specific experience with fluoroquinolone prophylaxis.

  3. Stem cell transplant: An experience from eastern India

    PubMed Central

    Mukhopadhyay, A.; Gupta, P.; Basak, J.; Chakraborty, A.; Bhattacharyya, D.; Mukhopadhyay, S.; Roy, U. K.

    2012-01-01

    Background: Hematopoietic stem cell transplant using human leukocyte antigen (HLA)-matched sibling or unrelated bone marrow, or related or unrelated cord blood has been performed successfully to treat patients with different types of hematological malignancies, genetic disorders and hereditary immune deficiencies. Since 1983, stem cell transplantation has been carried out in different institutes of India. But, till then, no transplantation was performed in eastern India. Materials and Methods: Our present study is reporting for the first time stem cell transplantation in eastern India. From August 2000 to June 2011 (with a 3-year gap for up-gradation), we have performed a total of 22 transplants. Thirteen patients (M:F:9:4) with indications of aplastic anemia, thalassaemia, acute myeloid leukemia and chronic myeloid leukemia underwent allogenic transplant, whereas autologous transplant was performed for nine patients (M:F:2:1) of multiple myeloma, Hodgkin's and non-Hodgkin's lymphoma and neuroblastoma. The median age of the patients was 19.6 years, with a range of 5 years 8 months to 52 years. Fourteen patients received myeloablative conditioning regime whereas eight patients received immunosuppressive and less myeloablative protocol. Sources of stem cells in case of allogenic transplant are bone marrow and related or unrelated umbilical cord blood and in case of autologous transplant, these are peripheral blood stem cells or self-bone marrow. Standard prophylactic medication was followed prior to transplants. Results: A disease-free survival of 68.18% and overall survival of 86.3% were seen at the median follow-up period of 4.6 years. Common post-transplant complications were mucositis, infection, venoocclusive disease, graft versus host disease, hemorrhagic cystitis, etc. Conclusion: The use of cord blood as a source of stem cells has been proved inferior as compared with the bone marrow stem cell source in cases of thalassaemia in our institute and thus is not

  4. The risk of transmitting cutaneous malignancy through skin transplantation: a literature-based risk assessment.

    PubMed

    Bosma, Sarah; Van Wijk, Marja J; Richters, Cornelia D; Beele, Hilde

    2015-12-01

    According to the European Union Tissues and Cells Directives donation of tissue is contraindicated in the presence of or a previous history of malignant disease, with the exception of cutaneous basal cell carcinoma. Skin cancer is the most common cancer. Due to ultraviolet light exposure and increasing life expectancy an increasing prevalence of malignant or premalignant skin lesions is observed, which may result in a decline of the availability of skin for transplantation. A risk assessment based on published studies and expert opinion was performed in order to investigate the risk of transmitting malignant or premalignant skin lesions through tissue transplantation, and more particular through skin transplantation. The scarcity of data concerning cancer transmission in tissue transplantation was challenging. Circumstantial evidence, available for organ transplantation, was used to develop the following policy proposal for skin transplantation and cutaneous tumours. Malignant melanoma is an absolute contraindication for the donation of skin and also of other tissues, whereas, non-lesional skin and other tissues of a donor with non-melanoma skin cancer (basal cell and squamous cell carcinoma) or with a premalignant skin lesion can be considered for transplantation. The above mentioned protocol proposal might serve as a prototype for analogous protocols for non-cutaneous malignancies.

  5. A Novel Health Information Technology Communication System to Increase Caregiver Activation in the Context of Hospital-Based Pediatric Hematopoietic Cell Transplantation: A Pilot Study.

    PubMed

    Maher, Molly; Hanauer, David A; Kaziunas, Elizabeth; Ackerman, Mark S; Derry, Holly; Forringer, Rachel; Miller, Kristen; O'Reilly, Dennis; An, Lawrence; Tewari, Muneesh; Choi, Sung Won

    2015-10-27

    Pediatric hematopoietic cell transplantation (HCT), commonly referred to as blood and marrow transplantation (BMT), is an intense treatment modality that requires the involvement of engaged caregivers during the patient's (child's) prolonged hospitalization. The ubiquity of electronic health records (EHRs) and a trend toward patient-centered care could allow a novel health information technology (IT) system to increase parental engagement. The paucity of research on acute care, hospital-based (inpatient) health IT applications for patients or caregivers provides an opportunity for testing the feasibility of such applications. The pediatric BMT population represents an ideal patient group to conduct an evaluation due to the lengthy inpatient stays and a heightened need for patient activation. The primary objective of this study is to assess the feasibility of implementing the BMT Roadmap in caregivers as an intervention during their child's inpatient hospitalization. The BMT Roadmap is an inpatient portal prototype optimized for tablet with a user-centered design. It integrates patient-specific laboratory and medication data from the EHR in real-time and provides support in terms of discharge goals, home care education, and other components. Feasibility will be proven if (1) the BMT Roadmap functions and can be managed by the study team without unexpected effort, (2) the system is accessed by users at a defined minimum threshold, and (3) the qualitative and quantitative research conducted provides quality data that address the perceived usefulness of the BMT Roadmap and could inform a study in a larger sample size. This will be a single-arm, nonrandomized feasibility study. We aim to enroll 10 adult caregivers (age ≥ 18 years) of pediatric patients (aged 0-25 years) undergoing autologous (self-donor) or allogeneic (alternative donor) BMT. Assenting minors (aged 10-18) will also be invited to participate. Recruitment of study participants will take place in the

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

    PubMed Central

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

    2016-01-01

    A record number of 40 829 hematopoietic stem cell transplantation (HSCT) in 36 469 patients (15 765 allogeneic (43%), 20 704 autologous (57%)) were reported by 656 centers in 47 countries to the 2014 survey. Trends include: continued growth in transplant activity, more so in Eastern European countries than in the west; a continued increase in the use of haploidentical family donors (by 25%) and slower growth for unrelated donor HSCT. The use of cord blood as a stem cell source has decreased again in 2014. Main indications for HSCT were leukemias: 11 853 (33% 96% allogeneic); lymphoid neoplasias; 20 802 (57% 11% allogeneic); solid tumors; 1458 (4% 3% allogeneic) and non-malignant disorders; 2203 (6% 88% allogeneic). Changes in transplant activity include more allogeneic HSCT for AML in CR1, myeloproliferative neoplasm (MPN) and aplastic anemia and decreasing use in CLL; and more autologous HSCT for plasma cell disorders and in particular for amyloidosis. In addition, data on numbers of teams doing alternative donor transplants, allogeneic after autologous HSCT, autologous cord blood transplants are presented. PMID:26901709

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

    PubMed

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

    2016-06-01

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

  8. [Stromal cell transplant in the 6-OHDA lesion model].

    PubMed

    Pavón-Fuentes, N; Blanco-Lezcano, L; Martínez-Martín, L; Castillo-Díaz, L; de la Cuétara-Bernal, K; García-Miniet, R; Lorigados-Pedre, L; Coro-Grave de Peralta, Y; García-Varona, A Y; Rosillo-Martí, J C; Macías-González, R

    A good deal of evidence currently exists to show that transplanting foetal mesencephalic tissue can produce symptomatic benefits both in patients and in disease models. Nevertheless, the technical and ethical difficulties involved in obtaining enough suitable foetal cerebral tissue have been a serious obstacle to its application. Stromal cells derived from bone marrow, due to their potential capacity to generate different types of cells, could be an ideal source of material for cell restoration in neurodegenerative diseases. Our aim was to evaluate the effect of transplanting stromal cells derived from bone marrow on the behaviour of 6-OHDA rats, when they are inserted into the striatum. In this study we used rats with a lesion in the substantia nigra induced by 6-hydroxydopamine, divided into several experimental groups. Rotary activity induced by D-amphetamine (5 mg/kg, intraperitoneally) was evaluated before and throughout the three months following the transplant in all the experimental groups, except in the group of healthy controls. Hemiparkinsonian rats received a total of 350 000 foetal ventral mesencephalic cells and 8 x 10(4) stromal cells/microL, which were implanted in the striatum. Animals with stromal cells transplanted in the body of the striatum significantly reduced the number of turns induced by amphetamine (p < 0.05); yet this reduction was not greater than that induced by foetal mesencephalic cell transplants. We were also unable to demonstrate any significant improvement in the motor skills of the forelimbs.

  9. Post-transplant adoptive T-cell immunotherapy

    PubMed Central

    Aqui, Nicole A.; June, Carl H.

    2008-01-01

    Immune reconstitution following haematopoietic stem cell transplantation (SCT) is an often slow and incomplete process that leads to increased risk of infection and malignant disease. Immunization in SCT is frequently unsuccessful due to the prolonged lymphopenia, especially of CD4 T cells, seen following transplant. The transfusion of T cells, also called ‘adoptive T-cell therapy’, has the potential to enhance anti-tumour and overall immunity, and augment vaccine efficacy in the post-transplant setting. Recent advances in tissue culture, cellular immunology and tumour biology are guiding new approaches to adoptive T-cell therapy. This chapter will discuss the challenges that face the field before adoptive T-cell therapy can be translated into routine clinical practice. PMID:18790452

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

    PubMed Central

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

    2011-01-01

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

  11. Tracking T-cell immune reconstitution after TCRαβ/CD19-depleted hematopoietic cells transplantation in children.

    PubMed

    Zvyagin, I V; Mamedov, I Z; Tatarinova, O V; Komech, E A; Kurnikova, E E; Boyakova, E V; Brilliantova, V; Shelikhova, L N; Balashov, D N; Shugay, M; Sycheva, A L; Kasatskaya, S A; Lebedev, Y B; Maschan, A A; Maschan, M A; Chudakov, D M

    2016-12-09

    αβT-cell-depleted allogeneic hematopoietic cell transplantation holds promise for the safe and accessible therapy of both malignant and non-malignant blood disorders. Here we employed molecular barcoding normalized T-cell receptor (TCR) profiling to quantitatively track T-cell immune reconstitution after TCRαβ-/CD19-depleted transplantation in children. We demonstrate that seemingly early reconstitution of αβT-cell counts 2 months after transplantation is based on only several hundred rapidly expanded clones originating from non-depleted graft cells. In further months, frequency of these hyperexpanded clones declines, and after 1 year the observed T-cell counts and TCRβ diversity are mostly provided by the newly produced T cells. We also demonstrate that high TCRβ diversity at day 60 observed for some of the patients is determined by recipient T cells and intrathymic progenitors that survived conditioning regimen. Our results indicate that further efforts on optimization of TCRαβ-/CD19-depleted transplantation protocols should be directed toward providing more efficient T-cell defense in the first months after transplantation.Leukemia advance online publication, 9 December 2016; doi:10.1038/leu.2016.321.

  12. Molecular Imaging of Stem Cell Transplantation for Liver Diseases: Monitoring, Clinical Translation, and Theranostics

    PubMed Central

    Petrella, Francesco; Nicosia, Luca

    2016-01-01

    Stem cell transplantation has been investigated to rescue experimental liver failure and is promising to offer an alternative therapy to liver transplantation for liver diseases treatment. Several clinical studies in this field have been carried out, but the therapeutic benefit of this treatment is still controversial. A major obstacle to developing stem cell therapies in clinic is being able to visualize the cells in vivo. Imaging modalities allow optimization of delivery, detecting cell survival and functionality by in vivo monitoring these transplanted graft cells. Moreover, theranostic imaging is a brand new field that utilizes nanometer-scale materials to glean diagnostic insight for simultaneous treatment, which is very promising to improve stem cell-based therapy for treatment of liver diseases. The aim of this review was to summarize the various imaging tools that have been explored with advanced molecular imaging probes. We also outline some recent progress of preclinical and clinical studies of liver stem cells transplantation. Finally, we discuss theranostic imaging for stem cells transplantation for liver dysfunction and future opportunities afforded by theranostic imaging. PMID:28070195

  13. Immunomodulation by Transplanted Human Embryonic Stem Cell-Derived Oligodendroglial Progenitors in Experimental Autoimmune Encephalomyelitis

    PubMed Central

    Kim, Heechul; Walczak, Piotr; Kerr, Candace; Galpoththawela, Chulani; Gilad, Assaf A.; Muja, Naser; Bulte, Jeff W.M.

    2013-01-01

    Transplantation of embryonic stem cells and their neural derivatives can lead to amelioration of the disease symptoms of experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS). Oligodendroglial progenitors (OPs), derived from human embryonic stem cells (hESC, HES-1), were labeled with superparamagnetic iron oxide and transduced with luciferase. At 7 days following induction of EAE in C57/BL6 mice, 1 × 106 cells were transplanted in the ventricles of C57/BL6 mice and noninvasively monitored by magnetic resonance and bioluminescence imaging. Cells were found to remain within the cerebroventricular system and did not survive for more than 10 days. However, EAE mice that received hESC-OPs showed a significant improvement in neurological disability scores (0.9 ± 0.2; n = 12) compared to that of control animals (3.3 ± 0.4; n = 12) at day 15 post-transplantation. Histopathologically, transplanted hESC-OPs generated TREM2-positive CD45 cells, increased TIMP-1 expression, confined inflammatory cells within the subarachnoid space, and gave rise to higher numbers of Foxp3-positive regulatory T cells in the spinal cord and spleen. Our results suggest that transplantation of hESC-OPs can alter the pathogenesis of EAE through immunomodulation, potentially providing new avenues for stem cell-based treatment of MS. PMID:22949039

  14. Desensitization for solid organ and hematopoietic stem cell transplantation

    PubMed Central

    Zachary, Andrea A; Leffell, Mary S

    2014-01-01

    Desensitization protocols are being used worldwide to enable kidney transplantation across immunologic barriers, i.e. antibody to donor HLA or ABO antigens, which were once thought to be absolute contraindications to transplantation. Desensitization protocols are also being applied to permit transplantation of HLA mismatched hematopoietic stem cells to patients with antibody to donor HLA, to enhance the opportunity for transplantation of non-renal organs, and to treat antibody-mediated rejection. Although desensitization for organ transplantation carries an increased risk of antibody-mediated rejection, ultimately these transplants extend and enhance the quality of life for solid organ recipients, and desensitization that permits transplantation of hematopoietic stem cells is life saving for patients with limited donor options. Complex patient factors and variability in treatment protocols have made it difficult to identify, precisely, the mechanisms underlying the downregulation of donor-specific antibodies. The mechanisms underlying desensitization may differ among the various protocols in use, although there are likely to be some common features. However, it is likely that desensitization achieves a sort of immune detente by first reducing the immunologic barrier and then by creating an environment in which an autoregulatory process restricts the immune response to the allograft. PMID:24517434

  15. Desensitization for solid organ and hematopoietic stem cell transplantation.

    PubMed

    Zachary, Andrea A; Leffell, Mary S

    2014-03-01

    Desensitization protocols are being used worldwide to enable kidney transplantation across immunologic barriers, i.e. antibody to donor HLA or ABO antigens, which were once thought to be absolute contraindications to transplantation. Desensitization protocols are also being applied to permit transplantation of HLA mismatched hematopoietic stem cells to patients with antibody to donor HLA, to enhance the opportunity for transplantation of non-renal organs, and to treat antibody-mediated rejection. Although desensitization for organ transplantation carries an increased risk of antibody-mediated rejection, ultimately these transplants extend and enhance the quality of life for solid organ recipients, and desensitization that permits transplantation of hematopoietic stem cells is life saving for patients with limited donor options. Complex patient factors and variability in treatment protocols have made it difficult to identify, precisely, the mechanisms underlying the downregulation of donor-specific antibodies. The mechanisms underlying desensitization may differ among the various protocols in use, although there are likely to be some common features. However, it is likely that desensitization achieves a sort of immune detente by first reducing the immunologic barrier and then by creating an environment in which an autoregulatory process restricts the immune response to the allograft. © 2014 The Authors. Immunological Reviews Published by John Wiley & Sons Ltd.

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

    PubMed

    Moreno Camacho, Asunción; Ruiz Camps, Isabel

    2014-01-01

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

  17. Schwann Cell Transplantation and Descending Propriospinal Regeneration after Spinal Cord Injury

    PubMed Central

    Deng, Ling-Xiao; Walker, Chandler; Xu, Xiao-Ming

    2014-01-01

    After spinal cord injury (SCI), poor ability of damaged axons of the central nervous system (CNS) to regenerate causes very limited functional recovery. Schwann cells (SCs) have been widely explored as promising donors for transplantation to promote axonal regeneration in the CNS including the spinal cord. Compared with other CNS axonal pathways, injured propriospinal tracts display the strongest regenerative response to SC transplantation. Even without providing additional neurotrophic factors, propriospinal axons can grow into the SC environment which is rarely seen in supraspinal tracts. Propriospinal tract has been found to respond to several important neurotrophic factors secreted by SCs. Therefore, the SC is considered to be one of the most promising candidates for cell-based therapies for SCI. Since many reviews have already appeared on topics of SC transplantation in SCI repair, this review will focus particularly on the rationale of SC transplantation in mediating descending propriospinal axonal regeneration as well as optimizing such regeneration by using different combinatorial strategies. PMID:25257034

  18. Peripheral blood stem cell transplantation for ischemic femoral head necrosis.

    PubMed

    Song, H-J; Lan, B-Sh; Cheng, B; Zhang, K-F; Yan, H-W; Wang, W-Zh; Gao, Z-Q

    2010-06-01

    Avascular necrosis of the femoral head (ANFH) is a highly mutilating disease. There is no effective way to treat femoral head ischemia. This study was designed to show the curative effects of peripheral blood stem cell transplantation to induce vascular regeneration and improve ischemic femoral head necrosis in rabbits. Twenty New Zealand white rabbits underwent ischemic femoral head necrosis in both hindlimbs using liquid-nitrogen refrigeration. One cohort of rats was intraperitoneally injected with granulocyte-specific colony-stimulating factor (250 microg/kg/d), and control animals received equivalent saline solution. The right side was used as the transplantation group and the left as the control. After separation of peripheral blood, a stem cell suspension was poured into the right femoral artery and saline solution into the left femoral artery. At 4 weeks after peripheral stem cell transplantation, standing ability and activity of the the transplanted right hindlimb were remarkably improved, but there were no obvious changes in the control limbs. The experimental rabbits underwent arteriography of bilateral femoral heads, which indicated increased and thickened blood supply to the transplanted right hindlimb compared with the left control. Peripheral blood stem cell transplantation improved ischemic femoral head necrosis.

  19. The emerging role of nanotechnology in cell and organ transplantation

    PubMed Central

    Tasciotti, Ennio; Cabrera, Fernando J.; Evangelopoulos, Michael; Martinez, Jonathan O.; Thekkedath, Usha R.; Kloc, Malgorzata; Ghobrial, Rafik M.; Li, Xian C.; Grattoni, Alessandro; Ferrari, Mauro

    2016-01-01

    Transplantation is often the only choice many patients have when suffering from end stage organ failure. Although the quality of life improves after transplantation, challenges such as organ shortages, necessary immunosuppression with associated complications and chronic graft rejection limits its wide clinical application. Nanotechnology has emerged in the past two decades as a field with the potential to satisfy clinical needs in the area of targeted and sustained drug delivery, non-invasive imaging, and tissue engineering. In this paper, we provide an overview of popular nanotechnologies and a summary of the current and potential uses of nanotechnology in cell and organ transplantation. PMID:27257995

  20. Impact of pre-transplant depression on outcomes of allogeneic and autologous hematopoietic stem cell transplantation.

    PubMed

    El-Jawahri, Areej; Chen, Yi-Bin; Brazauskas, Ruta; He, Naya; Lee, Stephanie J; Knight, Jennifer M; Majhail, Navneet; Buchbinder, David; Schears, Raquel M; Wirk, Baldeep M; Wood, William A; Ahmed, Ibrahim; Aljurf, Mahmoud; Szer, Jeff; Beattie, Sara M; Battiwalla, Minoo; Dandoy, Christopher; Diaz, Miguel-Angel; D'Souza, Anita; Freytes, Cesar O; Gajewski, James; Gergis, Usama; Hashmi, Shahrukh K; Jakubowski, Ann; Kamble, Rammurti T; Kindwall-Keller, Tamila; Lazarus, Hilard M; Malone, Adriana K; Marks, David I; Meehan, Kenneth; Savani, Bipin N; Olsson, Richard F; Rizzieri, David; Steinberg, Amir; Speckhart, Dawn; Szwajcer, David; Schoemans, Helene; Seo, Sachiko; Ustun, Celalettin; Atsuta, Yoshiko; Dalal, Jignesh; Sales-Bonfim, Carmem; Khera, Nandita; Hahn, Theresa; Saber, Wael

    2017-05-15

    To evaluate the impact of depression before autologous and allogeneic hematopoietic cell transplantation (HCT) on clinical outcomes post-transplantation. We analyzed data from the Center for International Blood and Marrow Transplant Research to compare outcomes after autologous (n = 3786) or allogeneic (n = 7433) HCT for adult patients with hematologic malignancies with an existing diagnosis of pre-HCT depression requiring treatment versus those without pre-HCT depression. Using Cox regression models, we compared overall survival (OS) between patients with or without depression. We compared the number of days alive and out of the hospital in the first 100 days post-HCT using Poisson models. We also compared the incidence of grade 2-4 acute and chronic graft-versus-host disease (GVHD) in allogeneic HCT. The study included 1116 (15%) patients with pre-transplant depression and 6317 (85%) without depression who underwent allogeneic HCT between 2008 and 2012. Pre-transplant depression was associated with lower OS (hazard ratio [HR], 1.13; 95% confidence interval [CI], 1.04-1.23; P = 0.004) and a higher incidence of grade 2-4 acute GVHD (HR, 1.25; 95% CI, 1.14-1.37; P < 0.0001), but similar incidence of chronic GVHD. Pre-transplant depression was associated with fewer days-alive-and-out-of-the hospital (means ratio [MR] = 0.97; 95% CI, 0.95-0.99; P = 0.004). There were 512 (13.5%) patients with Pre-transplant depression and 3274 (86.5%) without depression who underwent autologous HCT. Pre-transplant depression in autologous HCT was not associated with OS (HR, 1.15; 95% CI, 0.98-1.34; P = 0.096) but was associated with fewer days alive and out of the hospital (MR, 0.98; 95% CI, 0.97-0.99; P = 0.002). Pre-transplant depression was associated with lower OS and higher risk of acute GVHD among allogeneic HCT recipients and fewer days alive and out of the hospital during the first 100 days after autologous and allogeneic HCT. Patients with pre-transplant

  1. Corneal regeneration by transplantation of corneal epithelial cell sheets fabricated with automated cell culture system in rabbit model.

    PubMed

    Kobayashi, Toyoshige; Kan, Kazutoshi; Nishida, Kohji; Yamato, Masayuki; Okano, Teruo

    2013-12-01

    We have performed clinical applications of cell sheet-based regenerative medicine with human patients in several fields. In order to achieve the mass production of transplantable cell sheets, we have developed automated cell culture systems. Here, we report an automated robotic system utilizing a cell culture vessel, cell cartridge. The cell cartridge had two rooms for epithelial cells and feeder layer cells separating by porous membrane on which a temperature-responsive polymer was covalently immobilized. After pouring cells into this robotic system, cell seeding, medium change, and microscopic examination during culture were automatically performed according to the computer program. Transplantable corneal epithelial cell sheets were successfully fabricated in cell cartridges with this robotic system. Then, fabricated cell sheets were transplanted onto ocular surfaces of rabbit limbal epithelial stem cell deficiency model after 6-h transportation using a portable homothermal container to keep inner temperature at 36 °C. Within one week after transplantation, normal corneal epithelium was successfully regenerated. This automatic cell culture system would be useful for industrialization of tissue-engineered products for regenerative medicine.

  2. 3-D Imaging Reveals Participation of Donor Islet Schwann Cells and Pericytes in Islet Transplantation and Graft Neurovascular Regeneration.

    PubMed

    Juang, Jyuhn-Huarng; Kuo, Chien-Hung; Peng, Shih-Jung; Tang, Shiue-Cheng

    2015-02-01

    The primary cells that participate in islet transplantation are the endocrine cells. However, in the islet microenvironment, the endocrine cells are closely associated with the neurovascular tissues consisting of the Schwann cells and pericytes, which form sheaths/barriers at the islet exterior and interior borders. The two cell types have shown their plasticity in islet injury, but their roles in transplantation remain unclear. In this research, we applied 3-dimensional neurovascular histology with cell tracing to reveal the participation of Schwann cells and pericytes in mouse islet transplantation. Longitudinal studies of the grafts under the kidney capsule identify that the donor Schwann cells and pericytes re-associate with the engrafted islets at the peri-graft and perivascular domains, respectively, indicating their adaptability in transplantation. Based on the morphological proximity and cellular reactivity, we propose that the new islet microenvironment should include the peri-graft Schwann cell sheath and perivascular pericytes as an integral part of the new tissue.

  3. Neural stem cell transplantation promotes behavioral recovery in a photothrombosis stroke model.

    PubMed

    Ma, Junning; Gao, Junwei; Hou, Boru; Liu, Jixing; Chen, Sihua; Yan, Guizhong; Ren, Haijun

    2015-01-01

    Stem cell-based therapy provides a promising approach for treat stroke. Neural stem cells isolated from mice hippocampus possessing the capacity of differentiate into neurons and astrocytes both in vitro and vivo. Here, we investigated the capability of neural stem cell transplantation in photothrombosis stroke model. Nissl staining revealed that the cortical infarct significantly decreased by 16.32% (Vehicle: 27.93le: an mm(3), n=6, NSC: 23.37le: ai mm(3), n=6, P<0.05) in the NSC group compared with the vehicle. More over transplantation of neural stem cells significantly (P<0.01) improved neurological performance compared with vehicle. These results indicate that transplantation of neural stem cell is an effective therapy in ischemic stroke.

  4. Neural stem cell transplantation promotes behavioral recovery in a photothrombosis stroke model

    PubMed Central

    Ma, Junning; Gao, Junwei; Hou, Boru; Liu, Jixing; Chen, Sihua; Yan, Guizhong; Ren, Haijun

    2015-01-01

    Stem cell-based therapy provides a promising approach for treat stroke. Neural stem cells isolated from mice hippocampus possessing the capacity of differentiate into neurons and astrocytes both in vitro and vivo. Here, we investigated the capability of neural stem cell transplantation in photothrombosis stroke model. Nissl staining revealed that the cortical infarct significantly decreased by 16.32% (Vehicle: 27.93le: an mm3, n=6, NSC: 23.37le: ai mm3, n=6, P<0.05) in the NSC group compared with the vehicle. More over transplantation of neural stem cells significantly (P<0.01) improved neurological performance compared with vehicle. These results indicate that transplantation of neural stem cell is an effective therapy in ischemic stroke. PMID:26339348

  5. Cell transplantation in lumbar spine disc degeneration disease.

    PubMed

    Hohaus, C; Ganey, T M; Minkus, Y; Meisel, H J

    2008-12-01

    Low back pain is an extremely common symptom, affecting nearly three-quarters of the population sometime in their life. Given that disc herniation is thought to be an extension of progressive disc degeneration that attends the normal aging process, seeking an effective therapy that staves off disc degeneration has been considered a logical attempt to reduce back pain. The most apparent cellular and biochemical changes attributable to degeneration include a decrease in cell density in the disc that is accompanied by a reduction in synthesis of cartilage-specific extracellular matrix components. With this in mind, one therapeutic strategy would be to replace, regenerate, or augment the intervertebral disc cell population, with a goal of correcting matrix insufficiencies and restoring normal segment biomechanics. Biological restoration through the use of autologous disc chondrocyte transplantation offers a potential to achieve functional integration of disc metabolism and mechanics. We designed an animal study using the dog as our model to investigate this hypothesis by transplantation of autologous disc-derived chondrocytes into degenerated intervertebral discs. As a result we demonstrated that disc cells remained viable after transplantation; transplanted disc cells produced an extracellular matrix that contained components similar to normal intervertebral disc tissue; a statistically significant correlation between transplanting cells and retention of disc height could displayed. Following these results the Euro Disc Randomized Trial was initiated to embrace a representative patient group with persistent symptoms that had not responded to conservative treatment where an indication for surgical treatment was given. In the interim analyses we evaluated that patients who received autologous disc cell transplantation had greater pain reduction at 2 years compared with patients who did not receive cells following their discectomy surgery and discs in patients that

  6. Engraftment and regenerative effects of bone marrow stromal cell transplantation on damaged rat olfactory mucosa.

    PubMed

    Kwon, Jang-Woo; Jo, Hyo Gyeong; Park, Sang Man; Ku, Cheol Hyo; Park, Dong-Joon

    2016-09-01

    To develop a new therapeutic method to treat olfactory deficits, we investigated the engraftment and regenerative effects of transplanted bone marrow stromal cells (BMSCs) on damaged rat olfactory mucosa. To induce olfactory nerve degeneration, one side of the olfactory mucosa of Sprague-Dawley rats was damaged via Triton X-100 irrigation. Phosphate-buffered saline containing syngeneic BMSCs was injected into the olfactory mucosa for transplantation. PKH fluorescent cell dye labeling of BMSCs was used to monitor the transplanted cells. After transplantation of BMSCs, the thickness and regeneration of olfactory mucosa were analyzed using hematoxylin-eosin (H&E) staining. S100 immunohistochemical staining was used to measure nerve sheath regeneration. The increase in NGF (nerve growth factor) level in the olfactory mucosa was measured by Western blot analysis. Transplanted bone marrow stromal cells were engrafted to the lamia propria of damaged mucosa. The mean time for normalization of thickness and morphological recovery of the olfactory mucosa was 4 weeks in the therapeutic group and 9 weeks in the control group. S100 immunoreactivity was higher on the BMSC-treated side than on the control side. During regeneration, the expression of NGF increased in the olfactory mucosa of the experimental group. Based on these results, BMSC transplantation accelerated regeneration of olfactory mucosa damaged by Triton X-100, and NGF may be essential to this regenerative process.

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

    PubMed

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

    2014-09-01

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

  8. Role of NK, NKT cells and macrophages in liver transplantation

    PubMed Central

    Fahrner, René; Dondorf, Felix; Ardelt, Michael; Settmacher, Utz; Rauchfuss, Falk

    2016-01-01

    Liver transplantation has become the treatment of choice for acute or chronic liver disease. Because the liver acts as an innate immunity-dominant organ, there are immunological differences between the liver and other organs. The specific features of hepatic natural killer (NK), NKT and Kupffer cells and their role in the mechanism of liver transplant rejection, tolerance and hepatic ischemia-reperfusion injury are discussed in this review. PMID:27468206

  9. In utero hematopoietic cell transplantation: induction of donor specific immune tolerance and postnatal transplants

    PubMed Central

    Peranteau, William H.

    2014-01-01

    In utero hematopoietic cell transplantation (IUHCT) is a non-myeloablative non-immunosuppressive transplant approach that allows for donor cell engraftment across immunologic barriers. Successful engraftment is associated with donor-specific tolerance. IUHCT has the potential to treat a large number of congenital hematologic, immunologic, and genetic diseases either by achieving high enough engraftment levels following a single IUHCT or by inducing donor specific tolerance to allow for non-toxic same-donor postnatal transplants. This review evaluates donor specific tolerance induction achieved by IUHCT. Specifically it addresses the need to achieve threshold levels of donor cell engraftment following IUHCT to consistently obtain immunologic tolerance. The mechanisms of tolerance induction including partial deletion of donor reactive host T cells by direct and indirect antigen presentation and the role of regulatory T cells in maintaining tolerance are reviewed. Finally, this review highlights the promising clinical potential of in utero tolerance induction to provide a platform on which postnatal cellular and organ transplants can be performed without myeloablative or immunosuppressive conditioning. PMID:25429269

  10. Strength Training Following Hematopoietic Stem Cell Transplantation

    PubMed Central

    Hacker, Eileen Danaher; Larson, Janet; Kujath, Amber; Peace, David; Rondelli, Damiano; Gaston, Lisa

    2010-01-01

    Background Patients receiving high-dose chemotherapy and hematopoietic stem cell transplantation (HSCT) experience considerable reductions in physical activity and deterioration of their health status. Objective The purpose of this pilot study was to test the effects of strength training compared to usual activity on physical activity, muscle strength, fatigue, health status perceptions, and quality of life following HSCT. Interventions/Methods Nineteen subjects were randomized to the exercise or control group. Moderate intensity strength training began following discharge from the hospital. Dependent variables included physical activity, muscle strength, fatigue, health status perceptions and quality of life. Variables were measured prior to admission to the hospital for HSCT, day 8 following HSCT, and six weeks following discharge from the hospital. Results Significant time effects were noted for many variables with anticipated declines in physical activity, muscle strength, fatigue, and health status perceptions immediately after HSCT with subsequent improvements six weeks following hospital discharge. One group effect was noted with subjects in the exercise group reporting less fatigue than subjects in the control group. Although no significant interactions were detected, the trends suggest that the exercise group may be more physically active following the intervention compared to the usual activity group. Conclusions This study demonstrates the potential positive effects of strength training on physical activity, fatigue, and quality of life in people receiving high-dose chemotherapy and HSCT. Implications for Practice Preliminary evidence is provided for using strength training to enhance early recovery following HSCT. Elastic resistance bands are easy to use and relatively inexpensive. PMID:21116175

  11. Characterizing human herpes virus 6 following hematopoietic stem cell transplantation.

    PubMed

    Perissinotti, Anthony J; Gulbis, Alison; Shpall, Elizabeth J; Howell, Joshua

    2015-04-01

    Human herpes virus 6 reactivation occurs in approximately 50% of patients following hematopoietic stem cell transplant, however, the significance of human herpes virus 6 reactivation remains uncertain. A retrospective study was conducted analyzing clinical data of patients testing positive for human herpes virus 6 by quantitative polymerase chain reaction following hematopoietic stem cell transplant from 1 January 1998 to 1 October 2011. Data retrieved were used to describe the clinical course and outcome of human herpes virus 6 positive hematopoietic stem cell transplant patients. Sixty patients were identified who tested positive for human herpes virus 6 by polymerase chain reaction following hematopoietic stem cell transplant. A high proportion of patients were identified in this cohort with acute myeloid leukemia (28.3%), active disease (65%), transplanted with a matched unrelated donor (30%), ≥ 1 antigen mismatched (28.3%) matched unrelated donor, or an umbilical cord graft (25%), and those who received antithymocyte globulin (42.4%). Thirty-eight (63.3%) patients were treated for human herpes virus 6 with foscarnet alone or in combination with intravenous immunoglobulin, whereas 18 (30%) did not require treatment survival at Day 100 was 73.3%. This study suggests human herpes virus 6 reactivation occurs shortly after hematopoietic stem cell transplant (median of 25 days (interquartile range, 20-31.75) after hematopoietic stem cell transplant). Many potential risk factors are described in this report. Treatment of human herpes virus 6 predominately consisted of foscarnet with or without intravenous immunoglobulin; however, treatment of human herpes virus 6 was not always warranted. Furthermore, the effect of treatment on patient outcomes is uncertain. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  12. Stem Cell Microencapsulation for Phenotypic Control, Bioprocessing, and Transplantation

    PubMed Central

    Wilson, Jenna L.

    2014-01-01

    Cell microencapsulation has been utilized for decades as a means to shield cells from the external environment while simultaneously permitting transport of oxygen, nutrients, and secretory molecules. In designing cell therapies, donor primary cells are often difficult to obtain and expand to appropriate numbers, rendering stem cells an attractive alternative due to their capacities for self-renewal, differentiation, and trophic factor secretion. Microencapsulation of stem cells offers several benefits, namely the creation of a defined microenvironment which can be designed to modulate stem cell phenotype, protection from hydrodynamic forces and prevention of agglomeration during expansion in suspension bioreactors, and a means to transplant cells behind a semi-permeable barrier, allowing for molecular secretion while avoiding immune reaction. This review will provide an overview of relevant microencapsulation processes and characterization in the context of maintaining stem cell potency, directing differentiation, investigating scalable production methods, and transplanting stem cells for clinically relevant disorders. PMID:23239279

  13. Imaging transplanted stem cells in real time using an MRI dual-contrast method

    PubMed Central

    Ngen, Ethel J.; Wang, Lee; Kato, Yoshinori; Krishnamachary, Balaji; Zhu, Wenlian; Gandhi, Nishant; Smith, Barbara; Armour, Michael; Wong, John; Gabrielson, Kathleen; Artemov, Dmitri

    2015-01-01

    Stem cell therapies are currently being investigated for the repair of brain injuries. Although exogenous stem cell labelling with superparamagnetic iron oxide nanoparticles (SPIONs) prior to transplantation provides a means to noninvasively monitor stem cell transplantation by magnetic resonance imaging (MRI), monitoring cell death is still a challenge. Here, we investigate the feasibility of using an MRI dual-contrast technique to detect cell delivery, cell migration and cell death after stem cell transplantation. Human mesenchymal stem cells were dual labelled with SPIONs and gadolinium-based chelates (GdDTPA). The viability, proliferation rate, and differentiation potential of the labelled cells were then evaluated. The feasibility of this MRI technique to distinguish between live and dead cells was next evaluated using MRI phantoms, and in vivo using both immune-competent and immune-deficient mice, following the induction of brain injury in the mice. All results were validated with bioluminescence imaging. In live cells, a negative (T2/T2*) MRI contrast predominates, and is used to track cell delivery and cell migration. Upon cell death, a diffused positive (T1) MRI contrast is generated in the vicinity of the dead cells, and serves as an imaging marker for cell death. Ultimately, this technique could be used to manage stem cell therapies. PMID:26330231

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

    PubMed

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

    2004-05-01

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

  15. Post-transplant lymphoproliferative disorder following kidney transplantation: a population-based cohort study.

    PubMed

    Maksten, Eva Futtrup; Vase, Maja Ølholm; Kampmann, Jan; d'Amore, Francesco; Møller, Michael Boe; Strandhave, Charlotte; Bendix, Knud; Bistrup, Claus; Thiesson, Helle Charlotte; Søndergaard, Esben; Hamilton-Dutoit, Stephen; Jespersen, Bente

    2016-04-01

    Post-transplant lymphoproliferative disorder (PTLD) incidence is difficult to determine, mainly because both early and other lesions may go unrecognized and unregistered. Few studies have included systematic pathology review to maximize case identification and decide more accurately PTLD frequency after long-term post-transplantation follow-up. A retrospective population-based cohort study including all kidney transplant recipients at two Danish centres (1990-2011; population covered 3.1 million; 2175 transplantations in 1906 patients). Pathology reports were reviewed for all patient biopsies to identify possible PTLDs. Candidate PTLDs underwent histopathological review and classification. Seventy PTLD cases were identified in 2175 transplantations (3.2%). The incidence rate (IR) after first transplantation was 5.4 cases per 1000 patient-years (95% CI: 4.0-7.3). Most PTLDs were monomorphic (58.5%), or early lesions (21.5%). Excluding early lesions and patients <18 years, IR was 3.7 (95% CI: 2.9-5.5). Ten patients with PTLD were retransplanted, 2 developing further PTLDs. Post-transplant patient survival was inferior in patients with PTLD, while death-censored graft survival was not. Using registry data together with extensive pathological review and long follow-up, a rather high incidence of PTLD was found.

  16. Umbilical cord blood: an evolving stem cell source for sickle cell disease transplants.

    PubMed

    Shenoy, Shalini

    2013-05-01

    Allogeneic hematopoietic stem cell transplantation has proven benefit in controlling sickle cell disease-related vasculopathy and organ damage. Myeloablative matched sibling donor cord transplants have excellent outcomes in sickle cell disease. Unrelated donor transplant options are often deferred because of a lack of suitable human leukocyte antigen-matched donors, a problem especially relevant to minority populations. Umbilical cord blood transplantation allows for more mismatching from the graft-versus-host disease perspective and the donor pool is expandable with effort and education. Drawbacks such as increased rates of graft rejection, a fixed cell dose, delayed immune reconstitution, and transplant-related mortality have deterred unrelated cord transplant efforts. However, the transplant community continues to make enormous strides in this transplant realm in areas of immunogenetics, stem cell expansion, conditioning regimens, and supportive care. This has allowed the development of new studies that are currently ongoing, exploring ways to make cord blood transplantation successful and safer. The goal is to make unrelated donor cord blood transplantation for sickle cell disease merit early consideration in patients who stand to benefit from this approach.

  17. Therapeutically targeting astrocytes with stem and progenitor cell transplantation following traumatic spinal cord injury.

    PubMed

    Falnikar, Aditi; Li, Ke; Lepore, Angelo C

    2015-09-04

    Replacement of lost and/or dysfunctional astrocytes via multipotent neural stem cell (NSC) and lineage-restricted neural progenitor cell (NPC) transplantation is a promising therapeutic approach for traumatic spinal cord injury (SCI). Cell transplantation in general offers the potential to replace central nervous system (CNS) cell types, achieve remyelination, deliver missing gene products, promote and guide axonal growth, modulate the host immune response, deliver neuroprotective factors, and provide a cellular substrate for bridging the lesion site, amongst other possible benefits. A host of cell types that differ in their developmental stage, CNS region and species of derivation, as well as in their phenotypic potential, have been tested in a variety of SCI animal models. Historically in the SCI field, most pre-clinical NSC and NPC transplantation studies have focused on neuronal and oligodendrocyte replacement. However, much less attention has been geared towards targeting astroglial dysfunction in the inured spinal cord, despite the integral roles played by astrocytes in both normal CNS function and in the diseased nervous system. Despite the relative lack of studies, cell transplantation-based targeting of astrocytes dates back to some of the earliest transplant studies in SCI animal models. In this review, we will describe the history of work involving cell transplantation for targeting astrocytes in models of SCI. We will also touch on the current state of affairs in the field, as well as on important future directions as we move forward in trying to develop this approach into a viable strategy for SCI patients. Practical issues such as timing of delivery, route of transplantation and immunesuppression needs are beyond the scope of this review. This article is part of a Special Issue entitled SI: Spinal cord injury. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Therapeutically targeting astrocytes with stem and progenitor cell transplantation following traumatic spinal cord injury

    PubMed Central

    Falnikar, Aditi; Li, Ke; Lepore, Angelo C.

    2014-01-01

    Replacement of lost and/or dysfunctional astrocytes via multipotent neural stem cell (NSC) and lineage-restricted neural progenitor cell (NPC) transplantation is a promising therapeutic approach for traumatic spinal cord injury (SCI). Cell transplantation in general offers the potential to replace central nervous system (CNS) cell types, achieve remyelination, deliver missing gene products, promote and guide axonal growth, modulate the host immune response, deliver neuroprotective factors, and provide a cellular substrate for bridging the lesion site, amongst other possible benefits. A host of cell types that differ in their developmental stage, CNS region and species of derivation, as well as in their phenotypic potential, have been tested in a variety of SCI animal models. Historically in the SCI field, most pre-clinical NSC and NPC transplantation studies have focused on neuronal and oligodendrocyte replacement. However, much less attention has been geared towards targeting astroglial dysfunction in the inured spinal cord, despite the integral roles played by astrocytes in both normal CNS function and in the diseased nervous system. Despite the relative lack of studies, cell transplantation-based targeting of astrocytes dates back to some of the earliest transplant studies in SCI animal models. In this review, we will describe the history of work involving cell transplantation for targeting astrocytes in models of SCI. We will also touch on the current state of affairs in the field, as well as on important future directions as we move forward in trying to develop this approach into a viable strategy for SCI patients. Practical issues such as timing of delivery, route of transplantation and immunesuppression needs are beyond the scope of this review. PMID:25251595

  19. Islet and Stem Cell Encapsulation for Clinical Transplantation

    PubMed Central

    Krishnan, Rahul; Alexander, Michael; Robles, Lourdes; Foster 3rd, Clarence E.; Lakey, Jonathan R.T.

    2014-01-01

    Over the last decade, improvements in islet isolation techniques have made islet transplantation an option for a certain subset of patients with long-standing diabetes. Although islet transplants have shown improved graft function, adequate function beyond the second year has not yet been demonstrated, and patients still require immunosuppression to prevent rejection. Since allogeneic islet transplants have experienced some success, the next step is to improve graft function while eliminating the need for systemic immunosuppressive therapy. Biomaterial encapsulation offers a strategy to avoid the need for toxic immunosuppression while increasing the chances of graft function and survival. Encapsulation entails coating cells or tissue in a semipermeable biocompatible material that allows for the passage of nutrients, oxygen, and hormones while blocking immune cells and regulatory substances from recognizing and destroying the cell, thus avoiding the need for systemic immunosuppressive therapy. Despite advances in encapsulation technology, these developments have not yet been meaningfully translated into clinical islet transplantation, for which several factors are to blame, including graft hypoxia, host inflammatory response, fibrosis, improper choice of biomaterial type, lack of standard guidelines, and post-transplantation device failure. Several new approaches, such as the use of porcine islets, stem cells, development of prevascularized implants, islet nanocoating, and multilayer encapsulation, continue to generate intense scientific interest in this rapidly expanding field. This review provides a comprehensive update on islet and stem cell encapsulation as a treatment modality in type 1 diabetes, including a historical outlook as well as current and future research avenues. PMID:25148368

  20. Development of a Web-Based Intervention for Addressing Distress in Caregivers of Patients Receiving Stem Cell Transplants: Formative Evaluation With Qualitative Interviews and Focus Groups

    PubMed Central

    Joshi, Tanisha; Simoneau, Teresa; Kilbourn, Kristin; Carr, Alaina; Kutner, Jean; Laudenslager, Mark L

    2017-01-01

    Background Caregivers of cancer patients experience significant burden and distress including depression and anxiety. We previously demonstrated the efficacy of an eight session, in-person, one-on-one stress management intervention to reduce distress in caregivers of patients receiving allogeneic hematopoietic stem cell transplants (allo-HSCT). Objective The objective of this study was to adapt and enhance the in-person caregiver stress management intervention to a mobilized website (eg, tablet, smartphone, or computer-based) for self-delivery in order to enhance dissemination to caregiver populations most in need. Methods We used an established approach for development of a mhealth intervention, completing the first two research and evaluation steps: Step One: Formative Research (eg, expert and stakeholder review from patients, caregivers, and palliative care experts) and Step Two: Pretesting (eg, Focus Groups and Individual Interviews with caregivers of patients with autologous HSCT (auto-HSCT). Step one included feedback elicited for a mock-up version of Pep-Pal session one from caregiver, patients and clinician stakeholders from a multidisciplinary palliative care team (N=9 caregivers and patient stakeholders and N=20 palliative care experts). Step two included two focus groups (N=6 caregivers) and individual interviews (N=9 caregivers) regarding Pep-Pal’s look and feel, content, acceptability, and potential usability/feasibility. Focus groups and individual interviews were audio-recorded. In addition, individual interviews were transcribed, and applied thematic analysis was conducted in order to gain an in-depth understanding to inform the development and refinement of the mobilized caregiver stress management intervention, Pep-Pal (PsychoEducation and skills for Patient caregivers). Results Overall, results were favorable. Pep-Pal was deemed acceptable for caregivers of patients receiving an auto-HSCT. The refined Pep-Pal program consisted of 9 sessions

  1. Intrahippocampal transplantation of mesenchymal stromal cells promotes neuroplasticity.

    PubMed

    Coquery, Nicolas; Blesch, Armin; Stroh, Albrecht; Fernández-Klett, Francisco; Klein, Julia; Winter, Christine; Priller, Josef

    2012-10-01

    Multipotent mesenchymal stromal cells (MSC) secrete soluble factors that stimulate the surrounding microenvironment. Such paracrine effects might underlie the potential benefits of many stem cell therapies. We tested the hypothesis that MSC are able to enhance intrinsic cellular plasticity in the adult rat hippocampus. Rat bone marrow-derived MSC were labeled with very small superparamagnetic iron oxide particles (VSOP), which allowed for non-invasive graft localization by magnetic resonance imaging (MRI). Moreover, MSC were transduced with lentiviral vectors to express the green fluorescent protein (GFP). The effects of bilateral MSC transplantation on hippocampal cellular plasticity were assessed using the thymidine analogs 5-bromo-2'-deoxyuridine (BrdU) and 5-iodo-2'-deoxyuridine (IdU). Behavioral testing was performed to examine the consequences of intrahippocampal MSC transplantation on locomotion, learning and memory, and anxiety-like and depression-like behavior. We found that intrahippocampal transplantation of MSC resulted in enhanced neurogenesis despite short-term graft survival. In contrast, systemic administration of the selective serotonin re-uptake inhibitor citalopram increased cell survival but did not affect cell proliferation. Intrahippocampal transplantation of MSC did not impair behavioral functions in rats, but only citalopram exerted anti-depressant effects. This is the first study to examine the effects of intrahippocampal transplantation of allogeneic MSC on hippocampal structural plasticity and behavioral functions in rats combined with non-invasive cell tracking by MRI. We found that iron oxide nanoparticles can be used to detect transplanted MSC in the brain. Although graft survival was short, intrahippocampal transplantation of MSC resulted in long-term changes in hippocampal plasticity. Our results suggest that MSC can be used to stimulate adult neurogenesis.

  2. ABO blood group mismatched hematopoietic stem cell transplantation.

    PubMed

    Tekgündüz, Sibel Akpınar; Özbek, Namık

    2016-02-01

    Apart from solid organ transplantations, use of ABO-blood group mismatched (ABO-mismatched) donors is acceptable in hematopoietic stem cell transplantation (HSCT) patients. About 20-40% of allogeneic HSCT recipients will receive grafts from ABO-mismatched donors. ABO incompatible HSCT procedures are associated with immediate and late consequences, including but not restricted to acute or delayed hemolytic reactions, delayed red blood cell recovery, pure red cell aplasia and graft-versus-host disease. This review summarizes the current knowledge about consequences of ABO-mismatched HSCT in terms of associated complications and will evaluate its impact on important outcome parameters of HSCT.

  3. Myeloid-derived suppressor cells: natural regulators for transplant tolerance.

    PubMed

    Boros, Peter; Ochando, Jordi C; Chen, Shu-Hsia; Bromberg, Jonathan S

    2010-11-01

    Myeloid derived suppressor cells (MDSC) contribute to the negative regulation of immune response in cancer patients. This review summarizes results on important issues related to MDSC biology, including expansion and activation of MDSC, phenotype, and subsets as well pathways and different mechanisms by which these cells exert their suppressive effect. Recent observations suggesting that MDSC may have roles in transplant tolerance are presented. Although therapeutic targeting and destruction of MDCS is of primary interest in cancer patients, in transplantation it will instead be necessary to induce, expand, and activate these cells; thus current possibilities for in vitro generation of MDSC are also discussed.

  4. Dechorionation of medaka embryos and cell transplantation for the generation of chimeras.

    PubMed

    Porazinski, Sean R; Wang, Huijia; Furutani-Seiki, Makoto

    2010-12-22

    Medaka is a small egg-laying freshwater fish that allows both genetic and embryological analyses and is one of the three vertebrate model organisms in which genome-wide phenotype-driven mutant screens were carried out (1). Divergence of functional overlap of related genes between medaka and zebrafish allows identification of novel phenotypes that are unidentifiable in a single species (2), thus medaka and zebrafish are complementary for genetic dissection of the vertebrate genome functions. Manipulation of medaka embryos, such as dechorionation, mounting embryos for imaging and cell transplantation, are key procedures to work on both medaka and zebrafish in a laboratory. Cell transplantation examines cell autonomy of medaka mutations. Chimeras are generated by transplanting labeled cells from donor embryos into unlabeled recipient embryos. Donor cells can be transplanted to specific areas of the recipient embryos based on the fate maps (3) so that clones from transplanted cells can be integrated in the tissue of interest during development. Due to the hard chorion and soft embryos, manipulation of medaka embryos is more involved than in zebrafish. In this video, we show detailed procedures to manipulate medaka embryos.

  5. Neuroprotective effects of oligodendrocyte progenitor cell transplantation in premature rat brain following hypoxic-ischemic injury.

    PubMed

    Chen, Long-Xia; Ma, Si-Min; Zhang, Peng; Fan, Zi-Chuan; Xiong, Man; Cheng, Guo-Qiang; Yang, Yi; Qiu, Zi-Long; Zhou, Wen-Hao; Li, Jin

    2015-01-01

    Periventricular leukomalacia (PVL) is a common ischemic brain injury in premature infants for which there is no effective treatment. The objective of this study was to determine whether transplanted mouse oligodendrocyte progenitor cells (OPCs) have neuroprotective effects in a rat model of PVL. Hypoxia-ischemia (HI) was induced in 3-day-old rat pups by left carotid artery ligation, followed by exposure to 6% oxygen for 2.5 h. Animals were assigned to OPC transplantation or sham control groups and injected with OPCs or PBS, respectively, and sacrificed up to 6 weeks later for immunohistochemical analysis to investigate the survival and differentiation of transplanted OPCs. Apoptosis was evaluated by double immunolabeling of brain sections for caspase-3 and neuronal nuclei (NeuN), while proliferation was assessed using a combination of anti-Nestin and -bromodeoxyuridine antibodies. The expression of brain-derived neurotrophic factor (BDNF) and Bcl-2 was examined 7 days after OPC transplantation. The Morris water maze was used to test spatial learning and memory. The results showed that transplanted OPCs survived and formed a myelin sheath, and stimulated BDNF and Bcl-2 expression and the proliferation of neural stem cells (NSC), while inhibiting HI-induced neuronal apoptosis relative to control animals. Moreover, deficits in spatial learning and memory resulting from HI were improved by OPC transplantation. These results demonstrate an important neuroprotective role for OPCs that can potentially be exploited in cell-based therapeutic approaches to minimize HI-induced brain injury.

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

    PubMed

    Franchi, Federico; Rodriguez-Porcel, Martin

    2017-01-01

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

  7. Stem cell transplantation in Europe: trends and prospects.

    PubMed

    Tan, S S; Uyl-de Groot, C A; Huijgens, P C; Fibbe, W E

    2007-11-01

    The aim of the present study was to identify trends in numbers of European patients treated with autologous and allogeneic haematopoietic stem cell transplantation (HSCT) as well as to provide anticipated transplant rates for the upcoming years. The following indications were considered: haematological malignancies (acute leukaemias, myeloproliferative disorders, lymphoproliferative disorders and multiple myeloma), solid tumours and non-malignant diseases. Numbers of patients treated from 1990 to 2004 were extracted from the European Group for Blood and Marrow Transplantation database, extrapolated to 2012 using mathematic models and adjusted to the literature study and expert opinion. In Europe, a 13% raise in HSCT utilisation is to be expected from 2005 to 2010, mostly due to the growing application of reduced-intensity conditioning regimens followed by allogeneic HSCT. Growing transplant rates are likely to exert health expenditure budgets and put pressure on health care providers and health insurers in Europe. Therefore, the rapid expansion would ideally imply a simultaneous increase in HSCT budgets.

  8. Optimal benefits for hematopoietic stem cell transplantation: a consensus opinion.

    PubMed

    Maziarz, Richard T; Farnia, Stephanie; Martin, Patricia; Komanduri, Krishna V

    2014-11-01

    Variability in transplantation benefits may directly affect outcomes of individuals undergoing autologous or allogeneic hematopoietic stem cell transplantation procedures. The Financial Working Group of the National Marrow Donor Program-sponsored System Capacity Initiative addressed the issue of variable benefits and reviewed multiple transplantation benefit packages from both public and private payer organizations. On completion of the review, a consensus was obtained on defining a recipient benefit package that avoids major coverage gaps that could negatively influence patient outcomes. The recommendation was to encourage adoption of these benefits at a national level by payers, benefit brokers/consultants, and sales teams. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  9. [Human herpesvirus-6 associated with hematopoietic stem cell transplantation].

    PubMed

    Ogata, Masao

    2015-10-01

    Reactivation of human herpesvirus (HHV)-6B is a relatively common occurrence after allogeneic stem cell transplantation (SCT), and it is associated with the development of various post-transplant complications. HHV-6 encephalitis appears to be a significant, life-threatening complication caused by HHV-6B reactivation. HHV-6 encephalitis typically develops 2-6 weeks after SCT, and the symptoms are characterized by memory loss, seizures, and consciousness loss. Magnetic resonance imaging typically shows limbic encephalitis. Recent large-scale studies and a prospective study showed a similar incidence of HHV-6 encephalitis development, with 7.9-9.9% in cord blood transplant recipients and 0.5-1.2% in bone marrow or peripheral blood stem cell transplant recipients. Epidemiological studies suggest that post-transplant immune reactions such as GVHD, pre-engraftment immune reaction, or engraftment syndrome play important roles in the development of HHV-6 encephalitis. The mortality rate remains high, and even among survivors, many patients are left with serious neurological impairments, such as memory disturbance and seizures. Elucidation of the pathophysiology and establishment of appropriate prophylactic measures are necessary to overcome this serious complication. Besides encephalitis, associations between HHV-6 and various post-transplant complications have been reported, including pneumonitis, gastroenterocolitis, hepatitis, bone marrow suppression, and GVHD. Further investigations are needed to determine the role of HHV-6 in these complications.

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

    PubMed

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

    2014-04-01

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

  11. How I assess comorbidities before hematopoietic cell transplantation

    PubMed Central

    Sorror, Mohamed L.

    2013-01-01

    The hematopoietic cell transplantation-comorbidity index (HCT-CI) is a comorbidity tool suited for recipients of HCT. The index has been shown to sensitively capture the prevalence and magnitude of severity of various organ impairments before HCT and to provide valuable prognostic information after HCT. Many investigators have validated the discriminative power of the HCT-CI, but others have not. One concern is the consistency in comorbidity coding across different evaluators, particularly in view of the relatively recent addition of the HCT-CI to the transplant evaluation process. In this article, comorbidity scoring was tested across different evaluators, and only a fair interobserver agreement rate could be detected. To address these issues, a brief training program is proposed here, consisting of systematic methodology for data acquisition and consistent guidelines for comorbidity coding that were summarized in a Web-based calculator. In a validation patient cohort, this training program was shown to improve the interevaluator agreement on HCT-CI scores to an excellent rate with weighted κ values in the range of 0.89 to 0.97. This proposed training program will facilitate reliable assessment of comorbidities in the clinic and for research studies leading to standardization of the use of comorbidities in prediction of HCT outcomes. PMID:23355537

  12. Facial reconstruction by biosurgery: cell transplantation versus cell homing.

    PubMed

    Mao, Jeremy J; Stosich, Michael S; Moioli, Eduardo K; Lee, Chang Hun; Fu, Susan Y; Bastian, Barbara; Eisig, Sidney B; Zemnick, Candice; Ascherman, Jeffrey; Wu, June; Rohde, Christine; Ahn, Jeffrey

    2010-04-01

    The face distinguishes one human being from another. When the face is disfigured because of trauma, tumor removal, congenital anomalies, or chronic diseases, the patient has a strong desire for functional and esthetic restoration. Current practice of facial reconstruction using autologous grafts, synthetic fillers, and prostheses is frequently below the surgeon's and patient's expectations. Facial reconstruction is yet to take advantage of recent advances in seemingly unrelated fields of stem cell biology, chemical engineering, biomaterials, and tissue engineering. "Biosurgery," a new concept that we propose, will incorporate novel principles and strategies of bioactive cues, biopolymers, and/or cells to restore facial defects. Small facial defects can likely be reconstructed by cell homing and without cell transplantation. A critical advantage of cell homing is that agilely recruited endogenous cells have the potential to harness the host's innate capacity for regeneration, thus accelerating the rate of regulatory and commercialization processes for product development. Large facial defects, however, may not be restorable without cell delivery per our understanding at this time. New breakthrough in biosurgery will likely originate from integrated strategies of cell biology, cytokine biology, chemical engineering, biomaterials, and tissue engineering. Regardless of cell homing or cell delivery approaches, biosurgery not only will minimize surgical trauma and repetitive procedures, but also produce long-lasting results. At the same time, caution must be exercised against the development of products that lack scientific basis or dogmatic combination of cells, biomaterials, and biomolecules. Together, scientifically derived biosurgery will undoubtedly develop into new technologies that offer increasingly natural reconstruction and/or augmentation of the face.

  13. Facial Reconstruction by Biosurgery: Cell Transplantation Versus Cell Homing

    PubMed Central

    Stosich, Michael S.; Moioli, Eduardo K.; Lee, Chang Hun; Fu, Susan Y.; Bastian, Barbara; Eisig, Sidney B.; Zemnick, Candice; Ascherman, Jeffrey; Wu, June; Rohde, Christine; Ahn, Jeffrey

    2010-01-01

    The face distinguishes one human being from another. When the face is disfigured because of trauma, tumor removal, congenital anomalies, or chronic diseases, the patient has a strong desire for functional and esthetic restoration. Current practice of facial reconstruction using autologous grafts, synthetic fillers, and prostheses is frequently below the surgeon's and patient's expectations. Facial reconstruction is yet to take advantage of recent advances in seemingly unrelated fields of stem cell biology, chemical engineering, biomaterials, and tissue engineering. “Biosurgery,” a new concept that we propose, will incorporate novel principles and strategies of bioactive cues, biopolymers, and/or cells to restore facial defects. Small facial defects can likely be reconstructed by cell homing and without cell transplantation. A critical advantage of cell homing is that agilely recruited endogenous cells have the potential to harness the host's innate capacity for regeneration, thus accelerating the rate of regulatory and commercialization processes for product development. Large facial defects, however, may not be restorable without cell delivery per our understanding at this time. New breakthrough in biosurgery will likely originate from integrated strategies of cell biology, cytokine biology, chemical engineering, biomaterials, and tissue engineering. Regardless of cell homing or cell delivery approaches, biosurgery not only will minimize surgical trauma and repetitive procedures, but also produce long-lasting results. At the same time, caution must be exercised against the development of products that lack scientific basis or dogmatic combination of cells, biomaterials, and biomolecules. Together, scientifically derived biosurgery will undoubtedly develop into new technologies that offer increasingly natural reconstruction and/or augmentation of the face. PMID:19891541

  14. [Hematopoietic stem cell transplantation: is it an immunologic therapy?].

    PubMed

    Olaya Vargas, Alberto; Pérez Gonzáles, Oscar

    2003-01-01

    The graft-versus-tumor effect occurring after allogeneic (genetically different) haematopoietic cell transplantation for treating human malignancies, represents the clearest example of the power of the human immune system to eradicate cancer. Recent advances in our understanding of the immunobiology of stem-cell engraftment, tolerance and tumor eradication are allowing clinicians to better harness this powerful effect.

  15. Stem cell transplantation enhances endogenous brain repair after experimental stroke.

    PubMed

    Horie, Nobutaka; Hiu, Takeshi; Nagata, Izumi

    2015-01-01

    Stem cell transplantation for stroke treatment has been a promising therapy in small and large animal models, and many clinical trials are ongoing to establish this strategy in a clinical setting. However, the mechanism underlying functional recovery after stem cell transplantation has not been fully established and there is still a need to determine the ideal subset of stem cells for such therapy. We herein reviewed the recent evidences showing the underlying mechanism of functional recovery after cell transplantation, focusing on endogenous brain repair. First, angiogenesis/neovascularization is promoted by trophic factors including vascular endothelial growth factor secreted from stem cells, and stem cells migrated to the lesion along with the vessels. Second, axonal sprouting, dendritic branching, and synaptogenesis were enhanced altogether in the both ipsilateral and contralateral hemisphere remapping the pyramidal tract across the board. Finally, endogenous neurogenesis was also enhanced although little is known how much these neurogenesis contribute to the functional recovery. Taken together, it is clear that stem cell transplantation provides functional recovery via endogenous repair enhancement from multiple ways. This is important to maximize the effect of stem cell therapy after stroke, although it is still undetermined which repair mechanism is mostly contributed.

  16. A new immunodeficient pigmented retinal degenerate rat strain to study transplantation of human cells without immunosuppression

    PubMed Central

    Seiler, Magdalene J.; Aramant, Robert B.; Jones, Melissa K.; Ferguson, Dave L.; Bryda, Elizabeth C.

    2015-01-01

    Purpose The goal of this study was to develop an immunodeficient rat model of retinal degeneration (RD nude rats) that will not reject transplanted human cells. Methods SD-Tg(S334ter)3Lav females homozygous for a mutated mouse rhodopsin transgene were mated with NTac:NIH-Whn (NIH nude) males homozygous for the Foxn1rnu allele. Through selective breeding, a new stock, SD-Foxn1 Tg(S334ter)3Lav (RD nude) was generated such that all animals were homozygous for the Foxn1rnu allele and either homo- or hemizygous for the S334ter transgene. PCR-based assays for both the Foxn1rnu mutation and the S334ter transgene were developed for accurate genotyping. Immunodeficiency was tested by transplanting sheets of hESC-derived neural progenitor cells to the subretinal space of RD nude rats, and, as a control, NIH nude rats. Rats were killed between 8 and 184 days after surgery, and eye sections were analyzed for human, neuronal, and glial markers. Results After transplantation to RD nude and to NIH nude rats, hESC-derived neural progenitor cells differentiated to neuronal and glial cells, and migrated extensively from the transplant sheets throughout the host retina. Migration was more extensive in RD nude than in NIH nude rats. Already 8 days after transplantation, donor neuronal processes were found in the host inner plexiform layer. In addition, host glial cells extended processes into the transplants. The host retina showed the same photoreceptor degeneration pattern as in the immunocompetent SD-Tg(S334ter)3Lav rats. Recipients survived well after surgery. Conclusions This new rat model is useful for testing the effect of human cell transplantation on the restoration of vision without interference of immunosuppression. PMID:24817311

  17. Pre-transplant emotional support is associated with longer survival after allogeneic hematopoietic stem cell transplantation.

    PubMed

    Ehrlich, K B; Miller, G E; Scheide, T; Baveja, S; Weiland, R; Galvin, J; Mehta, J; Penedo, F J

    2016-12-01

    Emerging evidence suggests that psychosocial factors pre-transplant predict survival in cancer patients undergoing hematopoietic stem cell transplantation (HSCT). These studies, however, typically have small sample sizes, short-term follow ups or a limited panel of medical covariates. We extend this research in a large, well-characterized sample of transplant patients, asking whether patients' perceived emotional support and psychological distress predict mortality over 2 years. Prior to transplant, 400 cancer patients (55.5% males; 82.8% White; Mage=50.0 years; 67.0% leukemia, 20.0% lymphoma) were interviewed by a social caseworker, who documented the patients' perceived emotional support and psychological distress. Subsequently, patients received an allogeneic HSCT (51.0% matched-related donor, 42.0% matched-unrelated donor and 7.0% cord blood). HSCT outcomes were obtained from medical records. Controlling for demographic characteristics (age, sex, race/ethnicity and marital status) and medical confounders (disease type, conditioning regimen, remission status, cell dosage, donor and recipient CMV seropositivity, donor sex, comorbidities and disease risk), ratings of good emotional support pre-transplant predicted longer overall survival (hazard ratio (HR)=0.61, 95% confidence interval (CI), 0.42-0.91; P=0.013). Pre-transplant psychological distress was unrelated to survival, however (Ps>0.58). Emotional support was marginally associated with lower rates of treatment-related mortality (HR=0.58, CI, 0.32-1.05; P=0.073). These findings are consistent with the hypothesis that emotional support contributes to better outcomes following HSCT. Future studies should examine whether intervention efforts to optimize emotional resources can improve survival in cancer patients.

  18. Stem cell transplantation for treating stroke: status, trends and development.

    PubMed

    Huo, Wenxin; Liu, Xiaoyang; Tan, Cheng; Han, Yingying; Kang, Chunyang; Quan, Wei; Chen, Jiajun

    2014-09-01

    The developing approaches of thrombolytic therapy, endovascular treatment, neuroprotective therapy, and stem cell therapy have enabled breakthroughs in stroke treatment. In this study, we summarize and analyze trends and progress in stem cell transplantation for stroke treatment by retrieval of literature from Thomson Reuters Web of Science database, the NIH Clinical Trial Planning Grant Program, and Clinical Trials Registration Center in North America. In the last 10 years, there has been an increasing number of published articles on stem cell transplantation for stroke treatment. In particular, research from the USA and China has focused on stem cell transplantation. A total of 2,167 articles addressing stem cell transplantation for stroke treatment from 2004 to 2013 were retrieved from the Thomson Reuters Web of Science database. The majority of these articles were from the USA (854, 39.4%), with the journal Stroke publishing the most articles (145, 6.7%). Of the published articles, 143 were funded by the National Institutes of Health (accounting for 6.6% of total publications), and 91 by the National Natural Science Foundation of China. Between 2013 and 2014, the National Institutes of Health provided financial support ($130 million subsidy) for 329 research projects on stroke therapy using stem cell transplantation. In 2014, 215 new projects were approved, receiving grants of up to $70,440,000. Ninety clinical trials focusing on stem cell transplantation for stroke were registered in the Clinical Trial Registration Center in North America, with 40 trials registered in the USA (ranked first place). China had the maximum number of registered research or clinical trials (10 projects).

  19. First example of hepatocyte transplantation to alleviate ornithine transcarbamylase deficiency, monitored by NMR-based metabonomics.

    PubMed

    Legido-Quigley, Cristina; Cloarec, Olivier; Parker, David A; Murphy, Gerard M; Holmes, Elaine; Lindon, John C; Nicholson, Jeremy K; Mitry, Ragai R; Vilca-Melendez, Hector; Rela, Mohamed; Dhawan, Anil; Heaton, Nigel

    2009-12-01

    We demonstrate the effective use of NMR spectroscopic profiles of urine and plasma from the first successful use of hepatocyte transplantation as a bridge to auxiliary partial orthotopic liver transplantation in a child antenatally diagnosed with severe ornithine transcarbamylase deficiency. In this single-patient study, NMR profiles indicated that the disrupted urea cycle could be normalized by hepatocyte cell infusion and this was confirmed using orthogonal partial least-squares-based chemometrics. However, despite dietary manipulations and adminstration of ammonia scavengers, the desired reduction in plasma ammonia was not consistently achieved between sessions of hepatocyte transplantation due to episodes of sepsis. A subsequent liver transplant corrected the metabolic abnormalities. The use of metabolic profiling has been shown to be a promising method for evaluating the efficacy of cell infusions and has demonstrated the capability for the early detection of response to therapy in real time, an approach that may be of use in wider clinical settings.

  20. Related cord blood banking for haematopoietic stem cell transplantation.

    PubMed

    Screnci, M; Murgi, E; Carmini, D; Piro, L; Cinelli, N; Laurenti, L; Iori, A P; Simone, F; Massari, S; Girelli, G

    2010-06-01

    The aims of this single centre study were to assess the feasibility of related cord blood collecting, the appropriateness of storage and the final suitability for transplantation. Since September 1994, 63 families were enrolled in this study. Families were eligible if they were caring for a patient with a disorder treatable by haematopoietic stem cell transplantation and were experiencing a pregnancy. A total of 72 cord blood units were collected and stored for 64 patients (both siblings and parents). We focussed on human leucocyte antigen (HLA) compatibility and cell content as critical requirements to unit's suitability for transplantation. HLA-typing was carried out for 34 donor-recipient couples and most units (72%) mismatched with the related patients. About 60% of collections had a minimum cell dose considered acceptable for transplantation. Only 21% of units had both compatibility degree and cell content suitable for transplantation. When applicable, information on the compatibility degree between the foetus and the patient should be obtained during pregnancy. Appropriateness of related cord blood banking for parents should be further investigated and cost-effective guidelines policies should be provided. Finally, as banking of related cord blood units is an important resource then, this public service should be supported and enhanced.

  1. Mycophenolate-based graft versus host disease prophylaxis is not inferior to methotrexate in myeloablative-related donor stem cell transplantation.

    PubMed

    Hamad, Nada; Shanavas, Mohamed; Michelis, Fotios V; Uhm, Jieun; Gupta, Vikas; Seftel, Matthew; Kuruvilla, John; Lipton, Jeffrey H; Messner, Hans A; Kim, Dennis Dong Hwan

    2015-05-01

    We retrospectively reviewed 242 patients who received related donor myeloablative peripheral blood hematopoietic cell transplantation. We compared patients who received mycophenolate (MMF)/cyclosporine (CSA) (n = 71), to historical controls who received methotrexate (MTX)/CSA (n = 172). There were no differences in overall survival, nonrelapse mortality, and relapse. The MMF/CSA group had significantly faster neutrophil and platelet engraftment: medians of 13 versus 18 days and 10 versus 14 days, respectively (P = 0.001). The cumulative incidence of acute graft versus host disease (GVHD) (Grades, 2-4) was significantly lower in the MMF/CSA group (45.1 vs. 74.4%, P < 0.001). The MMF/CSA group showed a lower incidence of skin (51.5 vs. 72.1%, P < 0.001) and liver acute GVHD (11.3 vs. 54.2%, P < 0.001) and a higher incidence of lung (42.2 vs. 19.0%, P = 0.045), eye (59.7 vs. 30.1%, P < 0.001), and mouth (72.8 vs. 56.4%, P = 0.001) chronic GVHD but only eye chronic GVHD was confirmed in propensity score matching (PSM) analysis. The incidence of cytomegalovirus (CMV) viremia was higher in the MMF/CSA group (55.8 vs. 39.6%, P < 0.001) but this was not confirmed in PSM analysis. MMF/CSA was identified as an independent favorable factor for acute GVHD (P < 0.001, hazard ratio, 0.41) but as a possible adverse risk factor for CMV viremia as this was not found to be statistically significant in PSM analysis. MMF/CSA in myeloablative matched related donor peripheral blood stem cell transplant is not inferior as GVHD prophylaxis in comparison with MTX/CSA and is associated with faster engraftment but a potentially higher risk of CMV viremia.

  2. Stem cell transplantation in strategies for curing HIV/AIDS.

    PubMed

    Hütter, Gero

    2016-01-01

    HIV-1 can persist in a latent form in resting memory CD4+ cells and macrophages carrying an integrated copy of the HIV genome. Because of the presence of these stable reservoir cells, eradication by antiretroviral therapy is unlikely and in order to achieve eradication, alternative treatment options are required. Stem cell transplantation has been considered previously to effect the clinical course of HIV-infection but in practice eradication or virus control was not achievable. However, modifications of stem cell transplantation using natural or artificial resistant cell sources, combination with new techniques of gene editing or generating cytotoxic anti HIV effector cells have stimulated this field of HIV cell therapy substantially. Here, we look back on 30 years of stem cell therapy in HIV patients and discuss most recent developments in this direction.

  3. The Past, Present, and Future of NK Cells in Hematopoietic Cell Transplantation and Adoptive Transfer.

    PubMed

    Cichocki, Frank; Verneris, Michael R; Cooley, Sarah; Bachanova, Veronika; Brunstein, Claudio G; Blazar, Bruce R; Wagner, John; Schlums, Heinrich; Bryceson, Yenan T; Weisdorf, Daniel J; Miller, Jeffrey S

    2016-01-01

    Hematopoietic cell transplantation (HCT) has been used as a part of cancer therapy for over half a decade. Beyond the necessity for donor-derived cells to reconstitute hematopoiesis after radiation and chemotherapy, immunologic reconstitution from allogeneic cells is important for the elimination of residual tumor cells. Natural killer (NK) cells are first among lymphocytes to reconstitute post-transplant and protect against cancer relapse. In this review, we provide a historical perspective on the role of NK cells in cancer control in the transplant setting and focus on current research aimed at improving NK cell responses for therapeutic benefit.

  4. Clinically applicable transplantation procedure of dermal papilla cells for hair follicle regeneration.

    PubMed

    Aoi, Noriyuki; Inoue, Keita; Kato, Harunosuke; Suga, Hirotaka; Higashino, Takuya; Eto, Hitomi; Doi, Kentaro; Araki, Jun; Iida, Takuya; Katsuta, Tomoya; Yoshimura, Kotaro

    2012-02-01

    Dermal papilla cells (DPCs) interact with epithelial stem cells and induce hair folliculogenesis. Cell-based therapies using expanded DPCs for hair regeneration have been unsuccessful in humans. Two major challenges remain: first, expanded DPCs obtained from adult hair follicles have functional limitations; second, a clinically applicable method is needed for transplanting DPCs. This study aimed to identify an efficient, minimally invasive and economical DPC transplantation procedure for use in clinical settings. Five clinically applicable transplantation procedures were tested, termed the Pinhole, Laser, Slit, Non-vascularized sandwich (NVS) and Hemi-vascularized sandwich (HVS) methods. Labelled rat dermal papilla tissue was transplanted into rat sole skin, and hair follicle regeneration was evaluated histologically. Regenerated follicles and labelled DPCs were detected for all methods, although some follicles showed abnormal growth, i.e. a cystic or inverted appearance. The HVS method, pioneered here, resulted in significantly larger number of regenerated follicles that were more mature and regular than those observed using the other methods. Moreover, hair growth was detected after expanded adult-derived DPC transplantation using the HVS method. These results suggest that direct contact of epithelial and dermal components and better vascularization/oxygenation of the recipient site are critical for hair regeneration in cell-based therapies. Copyright © 2011 John Wiley & Sons, Ltd.

  5. Children's Oncology Group's 2013 blueprint for research: stem cell transplantation.

    PubMed

    Grupp, Stephan A; Dvorak, Christopher C; Nieder, Michael L; Levine, John E; Wall, Donna A; Langholz, Bryan; Pulsipher, Michael A

    2013-06-01

    The role of SCT in pediatric oncology has continued to evolve with the introduction of new therapeutic agents and immunological insights into cancer. COG has focused its efforts on the study of hematopoietic stem cell transplantation in the treatment of pediatric malignancies in several major multi-institutional Phase II and Phase III studies. These studies include addressing the impact of allogenicity in ALL (ASCT0431), and establishing autologous stem cell transplant as the standard of care in neuroblastoma. Reducing transplant-associated toxicity was addressed in the ASCT0521 study, where the TNFα inhibitor etanercept was tested for the treatment of idiopathic pneumonia syndrome. Impact of cell dose was explored in the single versus tandem umbilical cord blood study CTN-0501, in close collaboration with the BMT-CTN.

  6. [Cell Transplantation in Age-related Macular Degeneration].

    PubMed

    Kirchhof, Bernd

    2017-09-01

    Robert Machemer offers a surgical approach to age-related macular degeneration with his retinal rotation. There is already considerable experimental and clinical knowledge available in Europe and the US on transplantation techniques for age-related macular degeneration. On average, initial visual acuity can be preserved. When photodynamic therapy was standard for exudative AMD, transplantation was superior. Photodynamic therapy could not stop, but was instead able to slow down visual loss. Currently, VEGF-blocker therapy has priority, because the visual acuity can be improved. However, this advantage does not last much longer than two years. Therefore, in the future, transplantation with new cells and less surgical risk may be reconsidered. At present, homologous RPE stem cells show promising results. They may be delivered as "sheets" or as single cells. For dry AMD only, a prophylactic approach seems reasonable, because, thus far, we are unable to reverse the atrophy on the retinal side. Georg Thieme Verlag KG Stuttgart · New York.

  7. Risk factors for Epstein-Barr virus-related post-transplant lymphoproliferative disease after allogeneic hematopoietic stem cell transplantation.

    PubMed

    Uhlin, Michael; Wikell, Helena; Sundin, Mikael; Blennow, Ola; Maeurer, Markus; Ringden, Olle; Winiarski, Jacek; Ljungman, Per; Remberger, Mats; Mattsson, Jonas

    2014-02-01

    Allogeneic hematopoietic stem cell transplantation is a successful treatment for hematologic malignancies and a variety of genetic and metabolic disorders. In the period following stem cell transplantation, the immune-compromised milieu allows opportunistic pathogens to thrive. Epstein-Barr virus-associated post-transplant lymphoproliferative disease can be a life-threatening complication for transplanted patients because of suppressed T-cell-mediated immunity. We analyzed possible risk factors associated with post-transplant lymphoproliferative disease in a cohort of over 1,000 patients. The incidence of post-transplant lymphoproliferative disease was 4%. Significant risk factors identified by multivariate analysis were: human leukocyte antigen-mismatch (P<0.001), serological Epstein-Barr virus mismatch recipient-/donor+ (P<0.001), use of reduced intensity conditioning (P=0.002), acute graft-versus-host disease grade II to IV (P=0.006), pre-transplant splenectomy (P=0.008) and infusion of mesenchymal stromal cells (P=0.015). The risk of post-transplant lymphoproliferative disease has increased in more recent years, from less than 2% before 1998 to more than 6% after 2011. Additionally, we show that long-term survival of patients with post-transplant lymphoproliferative disease is poor despite initial successful treatment. The 3-year survival rate among the 40 patients with post-transplant lymphoproliferative disease was 20% as opposed to 62% among patients without post-transplant lymphoproliferative disease (P<0.001). The study identifies patients at risk of post-transplant lymphoproliferative disease after transplantation in need of pre-emptive measures.

  8. Analysis of graft survival in a trial of stem cell transplant in ALS

    PubMed Central

    Tadesse, Tezeta; Gearing, Marla; Senitzer, David; Saxe, Debra; Brat, Daniel J; Bray, Robert; Gebel, Howard; Hill, Charles; Boulis, Nicholas; Riley, Jonathan; Feldman, Eva; Johe, Karl; Hazel, Thomas; Polak, Meraida; Bordeau, Jane; Federici, Thais; Glass, Jonathan D

    2014-01-01

    Objective The first US Food and Drug Administration–approved clinical trial to treat amyotrophic lateral sclerosis (ALS) with neural stem cell–based therapy is in progress. The goal of the current study was to identify and assess the survival of human spinal cord–derived neural stem cells (HSSCs) transplanted into the spinal cord in patients with ALS. Methods Spinal cords transplanted with HSSCs were examined from six autopsy cases. Homogenized tissues were interrogated for the presence of donor versus recipient DNA using real-time PCR methods (qPCR). Fluorescence in situ hybridization (FISH) was performed using DNA probes for XY chromosomes to identify male donor HSSCs in one female case, and immunohistochemistry (IHC) was used to characterize the identified donor cells. Results Genomic DNA from donor HSSCs was identified in all cases, comprising 0.67–5.4% of total tissue DNA in patients surviving 196 to 921 days after transplantation. In the one female patient a “nest” of cells identified on H&E staining were XY-positive by FISH, confirming donor origin. A subset of XY-positive cells labeled for the neuronal marker NeuN and stem cell marker SOX2. Interpretation This is the first study to identify human neural stem cells transplanted into a human spinal cord. Transplanted HSSCs survived up to 2.5 years posttransplant. Some cells differentiated into neurons, while others maintained their stem cell phenotype. This work is a proof of concept of the survival and differentiation of human stems cell transplanted into the spinal cord of ALS patients. PMID:25540804

  9. Iron Overload in Patients Undergoing Hematopoietic Stem Cell Transplantation

    PubMed Central

    Pullarkat, Vinod

    2010-01-01

    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. PMID:20871852

  10. Veno-occlusive disease in hematopoietic stem cell transplantation recipients.

    PubMed

    Sosa, Elisabeth C

    2012-10-01

    Veno-occlusive disease (VOD) is a potentially fatal complication of hematopoietic stem cell transplantation that affects the liver, as well as other organs. Although mild cases resolve on their own, severe cases of VOD carry a high mortality rate. The diagnosis usually is clinically based, with nonspecific signs such as weight gain, ascites, hepatomegaly, right upper quadrant abdominal pain, and elevated serum bilirubin. Although studies are ongoing, no U.S. Food and Drug Administration-approved treatments for VOD exist to date. Therefore, supportive care is a critical part of the treatment plan. Oncology nurses should be familiar with the risk factors and clinical signs of VOD so that patients can be monitored closely for its occurrence. Accurate and timely recognition of VOD is crucial for appropriate treatment.

  11. Intraperitoneal germ cell transplantation in the Nile tilapia Oreochromis niloticus.

    PubMed

    Farlora, Rodolfo; Hattori-Ihara, Shoko; Takeuchi, Yukata; Hayashi, Makoto; Octavera, Anna; Alimuddin; Yoshizaki, Goro

    2014-06-01

    Germ cell transplantation offers promising applications in finfish aquaculture and the preservation of endangered species. Here, we describe an intraperitoneal spermatogonia transplantation procedure in the Nile tilapia Oreochromis niloticus. Through histological analysis of early gonad development, we first determined the best suitable stage at which exogenous germ cells should be transplanted into the recipients. For the transplantation procedure, donor testes from a transgenic Nile tilapia strain carrying the medaka β-actin/enhanced green fluorescent protein (EGFP) gene were subjected to enzymatic dissociation. These testicular cells were then stained with PKH26 and microinjected into the peritoneal cavity of the recipient fish. To confirm colonization of the donor-derived germ cells, the recipient gonads were examined by fluorescent and confocal microscopy. PKH26-labeled cells exhibiting typical spermatogonial morphology were incorporated into the recipient gonads and were not rejected within 22 days posttransplantation. Long-term survival of transgenic donor-derived germ cells was then verified in the gonads of 5-month-old recipients and in the milt and vitelogenic oocytes of 1-year-old recipients, by means of PCR using EGFP-specific primers. EGFP-positive milt from adult male recipients was used to fertilize non-transgenic oocytes and produced transgenic offspring expressing the donor-derived phenotype. These results imply that long-term survival, proliferation, and differentiation of the donor-derived spermatogonia into vitelogenic oocytes and functional spermatozoa are all possible. Upon further improvements in the transplantation efficiency, this intraperitoneal transplantation system could become a valuable tool in the conservation of genetic resources for cichlid species.

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

    PubMed

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

    2016-02-01

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

  13. Belatacept Does Not Inhibit Follicular T Cell-Dependent B-Cell Differentiation in Kidney Transplantation

    PubMed Central

    de Graav, Gretchen N.; Hesselink, Dennis A.; Dieterich, Marjolein; Kraaijeveld, Rens; Verschoor, Wenda; Roelen, Dave L.; Litjens, Nicolle H. R.; Chong, Anita S.; Weimar, Willem; Baan, Carla C.

    2017-01-01

    Humoral alloreactivity has been recognized as a common cause of kidney transplant dysfunction. B-cell activation, differentiation, and antibody production are dependent on IL-21+CXCR5+follicular T-helper (Tfh) cells. Here, we studied whether belatacept, an inhibitor of the costimulatory CD28-CD80/86-pathway, interrupts the crosstalk between Tfh- and B-cells more efficiently than the calcineurin inhibitor tacrolimus. The suppressive effects of belatacept and tacrolimus on donor antigen-driven Tfh–B-cell interaction were functionally studied in peripheral blood mononuclear cells from 40 kidney transplant patients randomized to a belatacept- or tacrolimus-based immunosuppressive regimen. No significant differences in uncultured cells or donor antigen-stimulated cells were found between belatacept- and tacrolimus-treated patients in the CXCR5+Tfh cell generation and activation (upregulation of PD-1). Belatacept and tacrolimus in vitro minimally inhibited Tfh-cell generation (by ~6–7%) and partially prevented Tfh-cell activation (by ~30–50%). The proportion of IL-21+-activated Tfh-cells was partially decreased by in vitro addition of belatacept or tacrolimus (by ~60%). Baseline expressions and proportions of activated CD86+ B-cells, plasmablasts, and transitional B-cells after donor antigen stimulation did not differ between belatacept- and tacrolimus-treated patients. Donor antigen-driven CD86 upregulation on memory B-cells was not fully prevented by adding belatacept in vitro (~35%), even in supratherapeutic doses. In contrast to tacrolimus, belatacept failed to inhibit donor antigen-driven plasmablast formation (~50% inhibition vs. no inhibition, respectively, p < 0.0001). In summary, donor antigen-driven Tfh-B-cell crosstalk is similar in cells obtained from belatacept- and tacrolimus-treated patients. Belatacept is, however, less potent in vitro than tacrolimus in inhibiting Tfh-cell-dependent plasmablast formation. PMID:28620390

  14. Necrobiotic xanthogranuloma successfully treated with autologous stem cell transplantation.

    PubMed

    Goede, Jeroen S; Misselwitz, Benjamin; Taverna, Christian; Schanz, Urs; Dispenzieri, Angela; Hummel, Yvonne; Trüeb, Ralph M; Fehr, Jörg

    2007-04-01

    Paraproteinemia can be complicated by necrobiotic xanthogranuloma. Therapeutic options for this progressive disease are limited, and there is no agreement on a single best strategy. We report the case of a patient with a massive periorbital infiltration narrowing the palpebral fissure and blinding the patient. Conventional myeloma therapy had only limited benefit in our patient. However, he was successfully treated with high-dose chemotherapy followed by autologous stem cell transplantation, rendering the patient free of symptoms. This is the first report of autologous stem cell transplantation in a patient with necrobiotic xanthogranuloma.

  15. Antibiotic Doesn't Prevent Lung Complication After Stem Cell Transplant

    MedlinePlus

    ... html Antibiotic Doesn't Prevent Lung Complication After Stem Cell Transplant Findings were so dismal that clinical trial ... HealthDay News) -- An antibiotic treatment intended to lower stem cell transplant patients' risk of developing a respiratory complication ...

  16. Regulatory T cells in kidney disease and transplantation.

    PubMed

    Hu, Min; Wang, Yuan Min; Wang, Yiping; Zhang, Geoff Y; Zheng, Guoping; Yi, Shounan; O'Connell, Philip J; Harris, David C H; Alexander, Stephen I

    2016-09-01

    Regulatory T cells (Tregs) have been shown to be important in maintaining immune homeostasis and preventing autoimmune disease, including autoimmune kidney disease. It is also likely that they play a role in limiting kidney transplant rejection and potentially in promoting transplant tolerance. Although other subsets of Tregs exist, the most potent and well-defined Tregs are the Foxp3 expressing CD4(+) Tregs derived from the thymus or generated peripherally. These CD4(+)Foxp3(+) Tregs limit autoimmune renal disease in animal models, especially chronic kidney disease, and kidney transplantation. Furthermore, other subsets of Tregs, including CD8 Tregs, may play a role in immunosuppression in kidney disease. The development and protective mechanisms of Tregs in kidney disease and kidney transplantation involve multiple mechanisms of suppression. Here we review the development and function of CD4(+)Foxp3(+) Tregs. We discuss the specific application of Tregs as a therapeutic strategy to prevent kidney disease and to limit kidney transplant rejection and detail clinical trials in this area of transplantation.

  17. Red cell antibody problems in 1000 liver transplants

    PubMed Central

    Ramsey, G.; Cornell, F. W.; Hahn, L. F.; Larson, P.; Issitt, L. B.; Starzl, T. E.

    2010-01-01

    Liver transplant patients frequently require large amounts of blood. The frequency and nature of their red cell (RBC) antibody problems were examined. Records were reviewed in 496 adults and 286 children undergoing 1000 consecutive transplants. Twenty-two percent of adults and 14 percent of children had RBC alloantibodies. Antibodies of potential clinical significance were found before transplant in 6.3 percent of adults and 1.0 percent of children; despite immunosuppression, they appeared 1 to 5 weeks after transplant in an additional 7.5 and 5.2 percent respectively. These antibodies probably represented secondary immune responses. Of 58 transplant patients with prior potentially significant antibodies, 8 required 7 to 110 units of antigen-untyped blood after 8 to 28 units of antigen-negative blood; of these patients, one had subsequent hemolysis. Positive direct antiglobulin tests in 24 percent of adults and 10 percent of children were most often thought to be due to nonspecific adsorption of IgG. Anti-recipient ABO antibodies developed in 22 of 60 (37%) evaluable ABO-unmatched grafts; 13 cases had associated hemolysis. In all, 36 percent of adults and 20 percent of children had diverse RBC antibody problems. Resolution of these problems is an important part of the laboratory support necessary for a liver transplantation program. PMID:2660334

  18. Kidney Transplantation From a Donor With Sickle Cell Disease.

    PubMed

    Rossidis, A; Lim, M A; Palmer, M; Levine, M H; Naji, A; Bloom, R D; Abt, P L

    2017-02-01

    In the United States, >100 000 patients are waiting for a kidney transplant. Given the paucity of organs available for transplant, expansion of eligibility criteria for deceased donation is of substantial interest. Sickle cell disease (SCD) is viewed as a contraindication to kidney donation, perhaps because SCD substantially alters renal structure and function and thus has the potential to adversely affect multiple physiological processes of the kidney. To our knowledge, transplantation from a donor with SCD has never been described in the literature. In this paper, we report the successful transplantation of two kidneys from a 37-year-old woman with SCD who died from an intracranial hemorrhage. Nearly 4 mo after transplant, both recipients are doing well and are off dialysis. The extent to which kidneys from donors with SCD can be safely transplanted with acceptable outcomes is unknown; however, this report should provide support for the careful expansion of kidneys from donors with SCD without evidence of renal dysfunction and with normal tissue architecture on preimplantation biopsies.

  19. Transplantation of olfactory ensheathing cells to evaluate functional recovery after peripheral nerve injury.

    PubMed

    Guerout, Nicolas; Paviot, Alexandre; Bon-Mardion, Nicolas; Honoré, Axel; Obongo, Rais; Duclos, Célia; Marie, Jean-Paul

    2014-02-23

    Olfactory ensheathing cells (OECs) are neural crest cells which allow growth and regrowth of the primary olfactory neurons. Indeed, the primary olfactory system is characterized by its ability to give rise to new neurons even in adult animals. This particular ability is partly due to the presence of OECs which create a favorable microenvironment for neurogenesis. This property of OECs has been used for cellular transplantation such as in spinal cord injury models. Although the peripheral nervous system has a greater capacity to regenerate after nerve injury than the central nervous system, complete sections induce misrouting during axonal regrowth in particular after facial of laryngeal nerve transection. Specifically, full sectioning of the recurrent laryngeal nerve (RLN) induces aberrant axonal regrowth resulting in synkinesis of the vocal cords. In this specific model, we showed that OECs transplantation efficiently increases axonal regrowth. OECs are constituted of several subpopulations present in both the olfactory mucosa (OM-OECs) and the olfactory bulbs (OB-OECs). We present here a model of cellular transplantation based on the use of these different subpopulations of OECs in a RLN injury model. Using this paradigm, primary cultures of OB-OECs and OM-OECs were transplanted in Matrigel after section and anastomosis of the RLN. Two months after surgery, we evaluated transplanted animals by complementary analyses based on videolaryngoscopy, electromyography (EMG), and histological studies. First, videolaryngoscopy allowed us to evaluate laryngeal functions, in particular muscular cocontractions phenomena. Then, EMG analyses demonstrated richness and synchronization of muscular activities. Finally, histological studies based on toluidine blue staining allowed the quantification of the number and profile of myelinated fibers. All together, we describe here how to isolate, culture, identify and transplant OECs from OM and OB after RLN section-anastomosis and how

  20. Insights and hopes in umbilical cord blood stem cell transplantations.

    PubMed

    Shahrokhi, Somayeh; Menaa, Farid; Alimoghaddam, Kamran; McGuckin, Colin; Ebtekar, Massoumeh

    2012-01-01

    Over 20.000 umblical cord blood transplantations (UCBT) have been carried out around the world. Indeed, UCBT represents an attractive source of donor hematopoietic stem cells (HSCs) and, offer interesting features (e.g., lower graft-versus-host disease) compared to bone marrow transplantation (BMT). Thereby, UCBT often represents the unique curative option against several blood diseases. Recent advances in the field of UCBT, consisted to develop strategies to expand umbilical stem cells and shorter the timing of their engraftment, subsequently enhancing their availability for enhanced efficacy of transplantation into indicated patients with malignant diseases (e.g., leukemia) or non-malignant diseases (e.g., thalassemia major). Several studies showed that the expansion and homing of UCBSCs depends on specific biological factors and cell types (e.g., cytokines, neuropeptides, co-culture with stromal cells). In this review, we extensively present the advantages and disadvantages of current hematopoietic stem cell transplantations (HSCTs), compared to UBCT. We further describe the importance of cord blood content and obstetric factors on cord blood selection, and report the recent approaches that can be undertook to improve cord blood stem cell expansion as well as engraftment. Eventually, we provide two majors examples underlining the importance of UCBT as a potential cure for blood diseases.

  1. Insights and Hopes in Umbilical Cord Blood Stem Cell Transplantations

    PubMed Central

    Shahrokhi, Somayeh; Menaa, Farid; Alimoghaddam, Kamran; McGuckin, Colin; Ebtekar, Massoumeh

    2012-01-01

    Over 20.000 umblical cord blood transplantations (UCBT) have been carried out around the world. Indeed, UCBT represents an attractive source of donor hematopoietic stem cells (HSCs) and, offer interesting features (e.g., lower graft-versus-host disease) compared to bone marrow transplantation (BMT). Thereby, UCBT often represents the unique curative option against several blood diseases. Recent advances in the field of UCBT, consisted to develop strategies to expand umbilical stem cells and shorter the timing of their engraftment, subsequently enhancing their availability for enhanced efficacy of transplantation into indicated patients with malignant diseases (e.g., leukemia) or non-malignant diseases (e.g., thalassemia major). Several studies showed that the expansion and homing of UCBSCs depends on specific biological factors and cell types (e.g., cytokines, neuropeptides, co-culture with stromal cells). In this review, we extensively present the advantages and disadvantages of current hematopoietic stem cell transplantations (HSCTs), compared to UBCT. We further describe the importance of cord blood content and obstetric factors on cord blood selection, and report the recent approaches that can be undertook to improve cord blood stem cell expansion as well as engraftment. Eventually, we provide two majors examples underlining the importance of UCBT as a potential cure for blood diseases. PMID:23258957

  2. Fever after peripheral blood stem cell infusion in haploidentical transplantation with post-transplant cyclophosphamide.

    PubMed

    Arango, Marcos; Combariza, Juan F

    2017-06-01

    Noninfection-related fever can occur after peripheral blood stem cell infusion in haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide. The objective of this study was to analyze the incidence of fever and characterize some clinical features of affected patients. A retrospective case-series study with 40 patients who received haploidentical hematopoietic stem cell transplantation was carried out. Thirty-three patients (82.5%) developed fever; no baseline characteristic was associated with its development. Median time to fever onset was 25.5h (range, 9.5-100h) and median peak temperature was 39.0°C (range, 38.1-40.5°C). Not a single patient developed hemodynamic or respiratory compromise that required admission to the intensive care unit. Fever was not explained by infection in any case. Ninety-one percent of the febrile episodes resolved within 96h of cyclophosphamide administration. No significant difference in overall survival, event-free survival, or graft versus host disease-free/relapse-free survival was found in the group of febrile individuals after peripheral blood stem cell infusion. Fever after peripheral blood stem cell infusion in this clinical setting was common; it usually subsides with cyclophosphamide administration. The development of fever was not associated with an adverse prognosis. Copyright © 2017 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.

  3. Symptoms after hospital discharge following hematopoietic stem cell transplantation.

    PubMed

    Oguz, Gamze; Akin, Semiha; Durna, Zehra

    2014-01-01

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

  4. The role of allogeneic stem cell transplantation in Hodgkin's lymphoma.

    PubMed

    Sureda, Anna; Domenech, E; Schmitz, N; Dreger, P

    2014-06-01

    The treatment of patients with classical Hodgkin's lymphoma relapsing after autologous stem cell transplantation represents a clear unmet need. Overall long-term outcome is not the same in these patients and therapeutic options in this setting are very heterogeneous and include salvage CT and/or RT followed or not by a second stem cell transplantation, palliative care, new drugs, or biological agents. Despite the absence of prospective, randomized, clinical trials, allogeneic stem cell transplantation either from a HLA identical sibling or a matched, unrelated donor represents an attractive option for those young patients with chemosensitive disease after being treated with a salvage protocol. The use of reduced intensity conditioning regimens has been able to drastically decrease nonrelapse mortality, although relapse rate remains a significant issue in this setting. More intense conditioning protocols could eventually decrease the relapse rate after the allogeneic procedure and, as indicated by a recent retrospective analysis of the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation, nonrelapse mortality does not represent a major problem nowadays for patients with multiply relapsed Hodgkin's lymphoma. Brentuximab vedotin is an antibody-drug conjugate that selectively delivers monomethyl auristatin E, an antimicrotubule agent, into CD30-expressing cells. Its use has been approved recently for patients with Hodgkin's lymphoma relapsing after autologous stem cell transplantation. As a single dose, brentuximab vedotin is able to achieve an objective response rate of 75 % with 34 % of the patients achieving a complete remission. Its widespread use will most certainly change the treatment paradigm of this subgroup of patients, either avoiding the allogeneic procedure in some patients or by increasing the group of potential candidates to an allogeneic transplant being used as a "bridge to allo." Additional information on long

  5. Effect of Irradiation on Incidence of Post-Transplant Lymphoproliferative Disorder after Hematopoietic Cell Transplantation in Miniature Swine.

    PubMed

    Matar, Abraham J; Patil, Aarti R; Al-Musa, Ahmad; Hanekamp, Isabel; Sachs, David H; Huang, Christene A; Duran-Struuck, Raimon

    2015-10-01

    Post-transplant lymphoproliferative disease (PTLD) is a major complication of clinical organ and cell transplantation. Conditioning and immunosuppressive regimens that significantly impair T cell immunity, including depleting antibodies and calcineurin inhibitors, increase the risk of PTLD after transplantation. Swine PTLD has been shown to closely resemble human PTLD in morphology, histology, and viral-driven reactivation of B cells. Previously, we reported high incidences of PTLD after hematopoietic cell transplantation (HCT) in miniature swine recipients conditioned with thymic irradiation (TI) in addition to T cell depletion and cyclosporine A monotherapy after transplantation. Replacement of TI with 100 cGy of total body irradiation resulted in similar numbers of B cells early post-transplantation, greater numbers of T cells at day 0, and markedly decreased incidence of PTLD, suggesting that a threshold number of T cells may be necessary to prevent subsequent B cell proliferation and development of overt PTLD. Results from this large cohort of animals provide insight into the important effect of irradiation and T cell immunity on the incidence of PTLD after HCT and reinforce the pig model as a valuable tool for the study of PTLD and HCT. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  6. B cells with regulatory properties in transplantation tolerance

    PubMed Central

    Durand, Justine; Chiffoleau, Elise

    2015-01-01

    Induction of tolerance remains a major goal in transplantation. Indeed, despite potent immunosuppression, chronic rejection is still a real problem in transplantation. The humoral response is an important mediator of chronic rejection, and numerous strategies have been developed to target either B cells or plasma cells. However, the use of anti-CD20 therapy has highlighted the beneficial role of subpopulation of B cells, termed regulatory B cells. These cells have been characterized mainly in mice models of auto-immune diseases but emerging literature suggests their role in graft tolerance in transplantation. Regulatory B cells seem to be induced following inflammation to restrain excessive response. Different phenotypes of regulatory B cells have been described and are functional at various differentiation steps from immature to plasma cells. These cells act by multiple mechanisms such as secretion of immuno-suppressive cytokines interleukin-10 (IL-10) or IL-35, cytotoxicity, expression of inhibitory receptors or by secretion of non-inflammatory antibodies. Better characterization of the development, phenotype and mode of action of these cells seems urgent to develop novel approaches to manipulate the different B cell subsets and the response to the graft in a clinical setting. PMID:26722647

  7. B cells with regulatory properties in transplantation tolerance.

    PubMed

    Durand, Justine; Chiffoleau, Elise

    2015-12-24

    Induction of tolerance remains a major goal in transplantation. Indeed, despite potent immunosuppression, chronic rejection is still a real problem in transplantation. The humoral response is an important mediator of chronic rejection, and numerous strategies have been developed to target either B cells or plasma cells. However, the use of anti-CD20 therapy has highlighted the beneficial role of subpopulation of B cells, termed regulatory B cells. These cells have been characterized mainly in mice models of auto-immune diseases but emerging literature suggests their role in graft tolerance in transplantation. Regulatory B cells seem to be induced following inflammation to restrain excessive response. Different phenotypes of regulatory B cells have been described and are functional at various differentiation steps from immature to plasma cells. These cells act by multiple mechanisms such as secretion of immuno-suppressive cytokines interleukin-10 (IL-10) or IL-35, cytotoxicity, expression of inhibitory receptors or by secretion of non-inflammatory antibodies. Better characterization of the development, phenotype and mode of action of these cells seems urgent to develop novel approaches to manipulate the different B cell subsets and the response to the graft in a clinical setting.

  8. Synthetic molecules that protect cells from anoikis and their use in cell transplantation.

    PubMed

    Frisco-Cabanos, Heidie L; Watanabe, Mizuki; Okumura, Naoki; Kusamori, Kosuke; Takemoto, Naohiro; Takaya, Junichiro; Sato, Shin-ichi; Yamazoe, Sayumi; Takakura, Yoshinobu; Kinoshita, Shigeru; Nishikawa, Makiya; Koizumi, Noriko; Uesugi, Motonari

    2014-10-13

    One of the major problems encountered in cell transplantation is the low level of survival of transplanted cells due to detachment-induced apoptosis, called anoikis. The present study reports on the chemical synthesis and biological evaluation of water-soluble molecules that protect suspended cells from anoikis. The synthetic molecules bind to and induce clusters of integrins and heparan-sulfate-bound syndecans, two classes of receptors that are important for extracellular matrix-mediated cell survival. Molecular biological analysis indicates that such molecules prolong the survival of suspended NIH3T3 cells, at least in part, by promoting clustering of syndecan-4 and integrin β1 on the cell surface, leading to the activation of small GTPase Rac-1 and Akt. In vivo experiments using animal disease models demonstrated the ability of the molecules to improve cell engraftment. The cluster-inducing molecules may provide a starting point for the design of new synthetic tools for cell-based therapy. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Mesenchymal stromal cells and hematopoietic stem cell transplantation.

    PubMed

    Bernardo, Maria Ester; Fibbe, Willem E

    2015-12-01

    Mesenchymal stromal cells (MSCs) comprise a heterogeneous population of multipotent cells that can be isolated from various human tissues and culture-expanded ex vivo for clinical use. Due to their immunoregulatory properties and their ability to secrete growth factors, MSCs play a key role in the regulation of hematopoiesis and in the modulation of immune responses against allo- and autoantigens. In light of these properties, MSCs have been employed in clinical trials in the context of hematopoietic stem cell transplantation (HSCT) to facilitate engraftment of hematopoietic stem cells (HSCs) and to prevent graft failure, as well as to treat steroid-resistant acute graft-versus-host disease (GvHD). The available clinical evidence derived from these studies indicates that MSC administration is safe. Moreover, promising preliminary results in terms of efficacy have been reported in some clinical trials, especially in the treatment of acute GvHD. In this review we critically discuss recent advances in MSC therapy by reporting on the most relevant studies in the field of HSCT. Copyright © 2015 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  10. Influence of coping style on symptom interference among adult recipients of hematopoietic stem cell transplantation.

    PubMed

    Schoulte, Joleen C; Lohnberg, Jessica A; Tallman, Benjamin; Altmaier, Elizabeth M

    2011-09-01

    To investigate the influence of coping style on interference caused by a variety of common post-treatment symptoms after hematopoietic stem cell transplantation. Longitudinal; secondary analysis of data from the original study that examined health-related quality-of-life variables (e.g., depression, well-being) in adult patients treated with conventional bone marrow transplantation or depleted T-cell bone marrow transplantation. Fifteen university medical centers in the United States. 105 adult recipients of hematopoietic stem cell transplantation. Patients were assessed via telephone-based interviews for coping style at baseline and for symptom interference in daily living six months post-treatment. Coping style and symptom interference. Neither age nor gender predicted symptom interference, with the exception of chronic graft-versus-host disease, where older patients experienced more interference at six months, and breathing symptoms, for which women experienced more interference than men at six months. Avoidant coping style at baseline predicted increased interference from symptoms, but emotion-focused and instrumental coping styles did not predict decreased interference. A generalized avoidant coping style before treatment increased interference from common cancer symptoms six months after hematopoietic stem cell transplantation. An intervention to teach alternate coping strategies should be implemented prior to treatment and tested for prevention of symptom-related life interference.

  11. Minimal Residual Disease Following Allogeneic Hematopoietic Stem Cell Transplantation

    PubMed Central

    Kröger, Nicolaus; Miyamura, Koichi; Bishop, Michael R.

    2010-01-01

    Minimal residual disease (MRD), both before and after transplant, is a clinically important yet relatively poorly defined aspect of allogeneic hematopoietic stem cell transplantation (alloHSCT). The clinical relevance of MRD in the context of alloHSCT has been demonstrated by its association with the development of clinical relapse. However, with the possible exception of chronic myeloid leukemia, the specific techniques, timing, frequency and clinical utility, relative to improvement in patient outcomes, for monitoring MRD in the setting of alloHSCT has yet to be clearly defined. A concise overview of monitoring techniques for detecting MRD, as well as treatment strategies and biologic and clinical research initiatives for MRD suggested by the National Cancer Institute 1st International Workshop on the Biology, Prevention, and Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation, is covered in this paper. PMID:21047560

  12. Transplantation and Stem Cell Therapy for Cerebellar Degenerations.

    PubMed

    Cendelin, Jan

    2016-02-01

    Stem cell-based and regenerative therapy may become a hopeful treatment for neurodegenerative diseases including hereditary cerebellar degenerations. Neurotransplantation therapy mainly aims to substitute lost cells, but potential effects might include various mechanisms including nonspecific trophic effects and stimulation of endogenous regenerative processes and neural plasticity. Nevertheless, currently, there remain serious limitations. There is a wide spectrum of human hereditary cerebellar degenerations as well as numerous cerebellar mutant mouse strains that serve as models for the development of effective therapy. By now, transplantation has been shown to ameliorate cerebellar function, e.g. in Purkinje cell degeneration mice, Lurcher mutant mice and mouse models of spinocerebellar ataxia type 1 and type 2 and Niemann-Pick disease type C. Despite the lack of direct comparative studies, it appears that there might be differences in graft development and functioning between various types of cerebellar degeneration. Investigation of the relation of graft development to specific morphological, microvascular or biochemical features of the diseased host tissue in various cerebellar degenerations may help to identify factors determining the fate of grafted cells and potential of their functional integration.

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

    PubMed Central

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

    2016-01-01

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

  14. Pre-transplant risk factors for cryptogenic organizing pneumonia/bronchiolitis obliterans organizing pneumonia after hematopoietic cell transplantation.

    PubMed

    Nakasone, H; Onizuka, M; Suzuki, N; Fujii, N; Taniguchi, S; Kakihana, K; Ogawa, H; Miyamura, K; Eto, T; Sakamaki, H; Yabe, H; Morishima, Y; Kato, K; Suzuki, R; Fukuda, T

    2013-10-01

    Cryptogenic organizing pneumonia (COP), previously known as bronchiolitis obliterans organizing pneumonia (BOOP), is a significant complication after allogeneic hematopoietic SCT (HCT). However, the pathogenesis of this complication has not yet been elucidated. Therefore, we identified the pre-transplant risk factors for the development of COP/BOOP using the Japan transplant registry database between 2005 and 2009. Among 9550 eligible recipients, 193 experienced COP/BOOP (2%). HLA disparity (odds ratio (OR) 1.51, P=0.05), female-to-male HCT (OR 1.53, P=0.023), and PBSC transplant (OR 1.84, P=0.0076) were significantly associated with an increased risk of COP/BOOP. On the other hand, BU-based myeloablative conditioning (OR 0.52, P=0.033), or fludarabine-based reduced-intensity conditioning (OR 0.50, P=0.0011) in comparison with a TBI-based regimen and in vivo T-cell depletion (OR 0.46, P=0.055) were associated with a lower risk. Of the 193 patients with COP/BOOP, 77 died, including non-relapse death in 46 (59%). Pulmonary failure and fatal infection accounted for 41% (n=19) and 26% (n=12) of the non-relapse death. Allogeneic immunity and conditioning toxicity could be associated with COP/BOOP. Prospective studies are required to elucidate the true risk factors for COP/BOOP and to develop a prophylactic approach.

  15. Proceedings: Immune Tolerance and Stem Cell Transplantation: A CIRM Mini-Symposium and Workshop Report.

    PubMed

    Talib, Sohel; Millan, Maria T; Jorgenson, Rebecca L; Shepard, Kelly A

    2015-01-01

    The mission of the California Institute for Regenerative Medicine (CIRM) is to accelerate stem cell treatments to patients with unmet medical needs. Immune rejection is one hurdle that stem cell therapies must overcome to achieve a durable and effective therapeutic benefit. In July 2014, CIRM convened a group of clinical investigators developing stem cell therapeutics, immunologists, and transplantation biologists to consider strategies to address this challenge. Workshop participants discussed current approaches for countering immune rejection in the context of organ transplant and cellular therapy and defined the risks, challenges, and opportunities for adapting them to the development of stem cell-based therapeutics. This effort led to the development of a Roadmap to Tolerance for allogeneic stem cell therapy, with four fundamental steps: (a) the need to identify "tolerance-permissive" immune-suppressive regimens to enable the eventual transition from current, drug-based approaches to a newer generation of technologies for inducing tolerance; (b) testing new biologics and small molecules for inducing tolerance in stem cell-based preclinical and clinical studies; (c) stimulation of efforts to develop novel therapeutic approaches to induce central and peripheral tolerance, including manipulation of the thymus, transplantation of purified stem cells, and cell therapy with T-regulatory cells; and (d) development of robust and sensitive immune monitoring technologies for identifying biomarkers of tolerance and rejection after allogeneic stem cell treatments in the clinical setting.

  16. Hematopoietic stem cell transplantation for patients with sickle cell disease: progress and future directions.

    PubMed

    Fitzhugh, Courtney D; Abraham, Allistair A; Tisdale, John F; Hsieh, Matthew M

    2014-12-01

    Research has solidified matched sibling marrow, cord blood, or mobilized peripheral blood as the best source for allogeneic hematopoietic stem cell transplantation for patients with sickle cell disease, with low graft rejection and graft-versus-host disease (GVHD) and high disease-free survival rates. Fully allelic matched unrelated donor is an option for transplant-eligible patients without HLA-matched sibling donors. Unrelated cord transplant studies reported high GVHD and low engraftment rates. Haploidentical transplants have less GVHD, but improvements are needed to increase the low engraftment rate. The decision to use unrelated cord blood units or haploidentical donors depends on institutional expertise.

  17. Autologous hematopoietic stem cell transplantation for systemic sclerosis.

    PubMed

    Milanetti, Francesca; Bucha, Jurate; Testori, Alessandro; Burt, Richard K

    2011-03-01

    Systemic sclerosis is a rare disorder manifesting as skin and internal organ fibrosis, a diffuse vasculopathy, inflammation, and features of autoimmunity. Patients with diffuse cutaneous disease or internal organ involvement have a poor prognosis with high mortality. To date no therapy has been shown to reverse the natural course of the disease. Immune suppressive drugs are commonly utilized to treat patients, but randomized trials have generally failed to demonstrate any long-term benefit. In phase I/II trials, autologous hematopoietic stem cell transplantation (HSCT) has demonstrated impressive reversal of skin fibrosis, improved functionality and quality of life, and stabilization of internal organ function, but initial studies were complicated by significant treatment-related mortality. Treatment-related mortality was reduced by better pre-transplant evaluation to exclude patients with compromised cardiac function and by treating patients earlier in disease, allowing selected patients the option of autologous HSCT treatment. There are currently three ongoing randomized trials of autologous HSCT for systemic sclerosis: ASSIST (American Systemic Sclerosis Immune Suppression versus Transplant), SCOT (scleroderma cyclophosphamide versus Transplant), and ASTIS (Autologous Stem cell Transplantation International Scleroderma). The results from these trials should clarify the role of autologous HSCT in the currently limited therapeutic arsenal of severe systemic sclerosis.

  18. Second Unrelated Donor Hematopoietic Cell Transplantation for Primary Graft Failure

    PubMed Central

    Schriber, Jeffrey; Agovi, Manza-A.; Ho, Vincent; Ballen, Karen K.; Bacigalupo, Andrea; Lazarus, Hillard M.; Bredeson, Christopher N.; Gupta, Vikas; Maziarz, Richard T.; Hale, Gregory A.; Litzow, Mark R.; Logan, Brent; Bornhauser, Martin; Giller, Roger H.; Isola, Luis; Marks, David I.; Rizzo, J. Douglas; Pasquini, Marcelo C.

    2010-01-01

    Failure to engraft donor cells is a devastating complication after allogeneic hematopoietic cell transplantation (HCT). We describe the results of 122 patients reported to the National Marrow Donor Program between 1990 and 2005, who received a second unrelated donor HCT after failing to achieve an absolute neutrophil count of ≥ 500/ μL without recurrent disease. Patients were transplanted for leukemia (n=83), myelodysplastic disorders (n=16), severe aplastic anemia (n=20) and o