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Stem Cells Translational Medicine Nov 2021Umbilical cord blood transplantation (UCBT) has been performed in the clinic for over 30 years. The biological and immunological characteristics of umbilical cord... (Review)
Review
Umbilical cord blood transplantation (UCBT) has been performed in the clinic for over 30 years. The biological and immunological characteristics of umbilical cord blood (UCB) have been re-recognized in recent years. UCB, previously considered medical waste, is rich in hematopoietic stem cells (HSCs), which are naïve and more energetic and more easily expanded than other stem cells. UCB has been identified as a reliable source of HSCs for allogeneic hematopoietic stem cell transplantation (allo-HSCT). UCBT has several advantages over other methods, including no harm to mothers and donors, an off-the-shelf product for urgent use, less stringent HLA match, lower incidence and severity of chronic graft-vs-host disease (GVHD), and probably a stronger graft-vs-leukemia effect, especially for minimal residual disease-positive patients before transplant. Recent studies have shown that the outcome of UCBT has been improved and is comparable to other types of allo-HSCT. Currently, UCBT is widely used in malignant, nonmalignant, hematological, congenital and metabolic diseases. The number of UCB banks and transplantation procedures increased exponentially before 2013. However, the number of UCBTs increased steadily in Asia and China but decreased in the United States and Europe year-on-year from 2013 to 2019. In this review, we focus on the development of UCBT over the past 30 years, the challenges it faces and the strategies for future improvement, including increasing UCB numbers, cord blood unit selection, conditioning regimens and GVHD prophylaxis for UCBT, and management of complications of UCBT.
Topics: Cord Blood Stem Cell Transplantation; Fetal Blood; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Transplantation Conditioning
PubMed: 34724722
DOI: 10.1002/sctm.20-0495 -
International Journal of Medical... 2018Results obtained from completed and on-going clinical studies indicate huge therapeutic potential of stem cell-based therapy in the treatment of degenerative, autoimmune... (Review)
Review
Results obtained from completed and on-going clinical studies indicate huge therapeutic potential of stem cell-based therapy in the treatment of degenerative, autoimmune and genetic disorders. However, clinical application of stem cells raises numerous ethical and safety concerns. In this review, we provide an overview of the most important ethical issues in stem cell therapy, as a contribution to the controversial debate about their clinical usage in regenerative and transplantation medicine. We describe ethical challenges regarding human embryonic stem cell (hESC) research, emphasizing that ethical dilemma involving the destruction of a human embryo is a major factor that may have limited the development of hESC-based clinical therapies. With previous derivation of induced pluripotent stem cells (iPSCs) this problem has been overcome, however current perspectives regarding clinical translation of iPSCs still remain. Unlimited differentiation potential of iPSCs which can be used in human reproductive cloning, as a risk for generation of genetically engineered human embryos and human-animal chimeras, is major ethical issue, while undesired differentiation and malignant transformation are major safety issues. Although clinical application of mesenchymal stem cells (MSCs) has shown beneficial effects in the therapy of autoimmune and chronic inflammatory diseases, the ability to promote tumor growth and metastasis and overestimated therapeutic potential of MSCs still provide concerns for the field of regenerative medicine. This review offers stem cell scientists, clinicians and patient's useful information and could be used as a starting point for more in-depth analysis of ethical and safety issues related to clinical application of stem cells.
Topics: Animals; Biomedical Research; Cell Culture Techniques; Cell Differentiation; Cell Transplantation; Chimera; Embryo, Mammalian; Genetic Engineering; Genetic Therapy; Human Embryonic Stem Cells; Humans; Induced Pluripotent Stem Cells; Mesenchymal Stem Cell Transplantation; Regenerative Medicine
PubMed: 29333086
DOI: 10.7150/ijms.21666 -
Nature Reviews. Neurology Jul 2017Autologous haematopoietic stem cell transplantation (AHSCT) is a multistep procedure that enables destruction of the immune system and its reconstitution from... (Review)
Review
Autologous haematopoietic stem cell transplantation (AHSCT) is a multistep procedure that enables destruction of the immune system and its reconstitution from haematopoietic stem cells. Originally developed for the treatment of haematological malignancies, the procedure has been adapted for the treatment of severe immune-mediated disorders. Results from ∼20 years of research make a compelling case for selective use of AHSCT in patients with highly active multiple sclerosis (MS), and for controlled trials. Immunological studies support the notion that AHSCT causes qualitative immune resetting, and have provided insight into the mechanisms that might underlie the powerful treatment effects that last well beyond recovery of immune cell numbers. Indeed, studies have demonstrated that AHSCT can entirely suppress MS disease activity for 4-5 years in 70-80% of patients, a rate that is higher than those achieved with any other therapies for MS. Treatment-related mortality, which was 3.6% in studies before 2005, has decreased to 0.3% in studies since 2005. Current evidence indicates that the patients who are most likely to benefit from and tolerate AHSCT are young, ambulatory and have inflammatory MS activity. Clinical trials are required to rigorously test the efficacy, safety and cost-effectiveness of AHSCT against highly active MS drugs.
Topics: Hematopoietic Stem Cell Transplantation; Humans; Multiple Sclerosis; Outcome and Process Assessment, Health Care
PubMed: 28621766
DOI: 10.1038/nrneurol.2017.81 -
Biological Research 2012Hematopoietic stem cell transplantation is the accepted therapy of choice for a variety of malignant and non-malignant diseases in children and adults. Initially...
Hematopoietic stem cell transplantation is the accepted therapy of choice for a variety of malignant and non-malignant diseases in children and adults. Initially developed as rescue therapy for a patient with cancer after high doses of chemotherapy and radiation as well as the correction of severe deficiencies in the hematopoietic system, it has evolved into an adoptive immune therapy for malignancies and autoimmune disorders. The procedure has helped to obtain key information about the bone marrow environment, the biology of hematopoietic stem cells and histocompatibility. The development of this new discipline has allowed numerous groups working around the world to cure patients of diseases previously considered lethal. Together with the ever growing list of volunteer donors and umbilical cord blood banks, this has resulted in life saving therapy for thousands of patients yearly. We present an overview of the procedure from its cradle to the most novel applications, as well as the results of the HSC transplant program developed at our institution since 1989.
Topics: Hematopoietic Stem Cell Transplantation; History, 20th Century; History, 21st Century; Humans; Tissue Donors; Tissue and Organ Procurement; Transplantation Conditioning; Transplantation, Autologous; Transplantation, Homologous
PubMed: 23283440
DOI: 10.4067/S0716-97602012000300012 -
Blood Oct 2021Omidubicel is an ex vivo expanded hematopoietic progenitor cell and nonexpanded myeloid and lymphoid cell product derived from a single umbilical cord blood unit. We... (Comparative Study)
Comparative Study Randomized Controlled Trial
Omidubicel is an ex vivo expanded hematopoietic progenitor cell and nonexpanded myeloid and lymphoid cell product derived from a single umbilical cord blood unit. We report results of a phase 3 trial to evaluate the efficacy of omidubicel compared with standard umbilical cord blood transplantation (UCBT). Between January 2017 and January 2020, 125 patients age 13 to 65 years with hematologic malignancies were randomly assigned to omidubicel vs standard UCBT. Patients received myeloablative conditioning and prophylaxis with a calcineurin inhibitor and mycophenolate mofetil for graft-versus-host disease (GVHD). The primary end point was time to neutrophil engraftment. The treatment arms were well balanced and racially diverse. Median time to neutrophil engraftment was 12 days (95% confidence interval [CI], 10-14 days) for the omidubicel arm and 22 days (95% CI, 19-25 days) for the control arm (P < .001). The cumulative incidence of neutrophil engraftment was 96% for patients receiving omidubicel and 89% for patients receiving control transplants. The omidubicel arm had faster platelet recovery (55% vs 35% recovery by 42 days; P = .028), had a lower incidence of first grade 2 to 3 bacterial or invasive fungal infection (37% vs 57%; P = .027), and spent more time out of hospital during the first 100 days after transplant (median, 61 vs 48 days; P = .005) than controls. Differences in GVHD and survival between the 2 arms were not statistically significant. Transplantation with omidubicel results in faster hematopoietic recovery and reduces early transplant-related complications compared with standard UCBT. The results suggest that omidubicel may be considered as a new standard of care for adult patients eligible for UCBT. The trial was registered at www.clinicaltrials.gov as #NCT02730299.
Topics: Adolescent; Adult; Cord Blood Stem Cell Transplantation; Female; Fetal Blood; Graft Survival; Graft vs Host Disease; Hematologic Neoplasms; Hematopoiesis; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Young Adult
PubMed: 34157093
DOI: 10.1182/blood.2021011719 -
Frontiers in Endocrinology 2020Usually poor ovarian response (POR) to gonadotropins reflects a diminished ovarian reserve (DOR) that gives place to few recruitable follicles despite aggressive... (Review)
Review
Usually poor ovarian response (POR) to gonadotropins reflects a diminished ovarian reserve (DOR) that gives place to few recruitable follicles despite aggressive stimulation. The reduction in the quantity and quality of the oocytes with advanced age is physiological. However, some women experience DOR much earlier and become prematurely infertile, producing an accelerated follicular depletion towards primary ovarian insufficiency (POI). Up to now, egg donation has been commonly used to treat their infertility. In the last thirty years, specialists in assisted reproduction have focused their attention on the final stages of folliculogenesis, those that depend on the action of gonadotrophins. Nevertheless, recently novel aspects have been known to act in the initial phases, with activating and inhibiting elements. activation (IVA) combining the stimulation of the ovarian Akt signaling pathway in ovarian cortex fragments with a method named Hippo-signaling disruption. Later, a simplification of the technique designated Drug-Free IVA have shown encouraging results in patients with POI. Another innovative therapeutic option in these patients is the infusion of bone marrow-derived stem cells (BMDSC) in order to supply an adequate ovarian niche to maintain and/or promote follicular rescue in patients with impaired or aged ovarian reserves. In this review, for the first time, both therapeutic options are addressed together in a common clinical setting. The aim of this review is to analyze the physiological aspects on which these innovative techniques are based; the preliminary results obtained up to now; and the possible therapeutic role that they may have in the future with DOR and POI patients.
Topics: Animals; Female; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Ovarian Follicle; Ovarian Reserve; Primary Ovarian Insufficiency; Stem Cell Transplantation
PubMed: 33716954
DOI: 10.3389/fendo.2020.617704 -
APMIS : Acta Pathologica,... Dec 2022Mucosal microbiotas and their role in stem cell transplantation. Patients with hematological disorders such as leukemia often undergo allogeneic hematopoietic stem cell... (Review)
Review
Mucosal microbiotas and their role in stem cell transplantation. Patients with hematological disorders such as leukemia often undergo allogeneic hematopoietic stem cell transplantation, and thereby receive stem cells from a donor for curation of disease. This procedure also involves immunosuppressive and antimicrobial treatments that disturb the important interactions between the microbiota and the immune system, especially at mucosal sites. After transplantation, bacterial diversity decreases together with a depletion of Clostridia, and shifts toward predominance of Proteobacteria. Infectious and inflammatory complications, such as graft-versus-host disease, also interfere with patient recovery. This review collects and contextualizes current knowledge of the role of mucosal microbiotas at different body sites in stem cell transplantation, proposes underlying mechanisms, and discusses potential clinical value of bacterial markers for improved treatment strategies.
Topics: Humans; Transplantation, Homologous; Hematopoietic Stem Cell Transplantation; Graft vs Host Disease; Microbiota; Stem Cell Transplantation
PubMed: 35060190
DOI: 10.1111/apm.13208 -
Biology of Blood and Marrow... Dec 2020Optimal cord blood (CB) unit selection is critical to maximize the likelihood of successful engraftment and survival after CB transplantation (CBT). However, unit... (Review)
Review
Optimal cord blood (CB) unit selection is critical to maximize the likelihood of successful engraftment and survival after CB transplantation (CBT). However, unit selection can be complex because multiple characteristics must be considered including unit cell dose, donor-recipient human leukocyte antigen (HLA) match, and unit quality. This review provides evidence-based and experience-based comprehensive guidelines for CB unit selection. Topics addressed include the use of both the TNC and the CD34 cell dose, as well as the CD34 cell to TNC content ratio to evaluate unit progenitor cell content and engraftment potential, the acceptable TNC and CD34 cell dose criteria that define an adequate single-unit graft, and the indication and acceptable cell dose criteria for double-unit grafts. The acceptable criteria for 6-loci (HLA-A, -B antigen, -DRB1 allele) and 8-allele (HLA-A, -B, -C, -DRB1) donor-recipient HLA match, the evaluation of patients with donor-specific HLA antibodies, and the multiple determinants of unit quality are also reviewed in detail. Finally, a practical step-by-step guide to CB searches and the principles that guide ultimate graft selection are outlined.
Topics: Cord Blood Stem Cell Transplantation; Fetal Blood; HLA Antigens; Hematopoietic Stem Cell Transplantation; Histocompatibility Testing; Humans; Tissue Donors
PubMed: 32736011
DOI: 10.1016/j.bbmt.2020.07.030 -
Brain : a Journal of Neurology Nov 2017The availability of multiple disease-modifying medications with regulatory approval to treat multiple sclerosis illustrates the substantial progress made in therapy of... (Review)
Review
The availability of multiple disease-modifying medications with regulatory approval to treat multiple sclerosis illustrates the substantial progress made in therapy of the disease. However, all are only partially effective in preventing inflammatory tissue damage in the central nervous system and none directly promotes repair. Cell-based therapies, including immunoablation followed by autologous haematopoietic stem cell transplantation, mesenchymal and related stem cell transplantation, pharmacologic manipulation of endogenous stem cells to enhance their reparative capabilities, and transplantation of oligodendrocyte progenitor cells, have generated substantial interest as novel therapeutic strategies for immune modulation, neuroprotection, or repair of the damaged central nervous system in multiple sclerosis. Each approach has potential advantages but also safety concerns and unresolved questions. Moreover, clinical trials of cell-based therapies present several unique methodological and ethical issues. We summarize here the status of cell-based therapies to treat multiple sclerosis and make consensus recommendations for future research and clinical trials.
Topics: Hematopoietic Stem Cell Transplantation; Humans; Induced Pluripotent Stem Cells; Mesenchymal Stem Cell Transplantation; Multiple Sclerosis; Myelin Sheath; Oligodendroglia; Regeneration; Stem Cell Transplantation; Stem Cells; Transplantation, Autologous
PubMed: 29053779
DOI: 10.1093/brain/awx154 -
Virulence Nov 2016
Topics: Animals; Hematopoietic Stem Cell Transplantation; Humans; Transplantation, Homologous
PubMed: 27791470
DOI: 10.1080/21505594.2016.1252019