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Veterinary Medicine and Science Nov 2021Pre-clinical haematopoietic cell transplantation (HCT) studies in canines have proven to be invaluable for establishing HCT as a highly successful clinical option for... (Review)
Review
Pre-clinical haematopoietic cell transplantation (HCT) studies in canines have proven to be invaluable for establishing HCT as a highly successful clinical option for the treatment of malignant and non-malignant haematological diseases in humans. Additionally, studies in canines have shown that immune tolerance, established following HCT, enabled transplantation of solid organs without the need of lifelong immunosuppression. This progress has been possible due to multiple biological similarities between dog and mankind. In this review, the hurdles that were overcome and the methods that were developed in the dog HCT model which made HCT clinically possible are examined. The results of these studies justify the question whether HCT can be used in the veterinary clinical practice for more wide-spread successful treatment of canine haematologic and non-haematologic disorders and whether it is prudent to do so.
Topics: Animals; Dog Diseases; Dogs; Hematologic Diseases; Hematopoietic Stem Cell Transplantation; Organ Transplantation
PubMed: 34390541
DOI: 10.1002/vms3.601 -
Cell Transplantation Jan 2019Spinal cord injury (SCI) is a devastating disease, with a high rate of disability. In this meta-analysis, we aimed to comprehensively assess the efficacy and safety of... (Meta-Analysis)
Meta-Analysis Review
Spinal cord injury (SCI) is a devastating disease, with a high rate of disability. In this meta-analysis, we aimed to comprehensively assess the efficacy and safety of mesenchymal stem cells (MSCs) in treating clinical SCI patients. We systematically searched the PUBMED, EMBASE, Chinese Biomedical (CBM), Web of Science and Cochrane databases using the strategy of combination of free-text words and MeSH terms. The indicators of the American Spinal Injury Association (ASIA) impairment scale (AIS)-grading improvement rate and adverse effects were displayed with an overall relative risk (RR). For the continuous variables of the ASIA motor score, light-touch score, pinprick score, activities of daily living (ADL) score, and residual urine volume, we used odds ratio (OR) to analyze the data. Eleven studies comprising 499 patients meeting all inclusion and exclusion criteria were included. No serious heterogeneity or publication bias was observed across each study. The results showed that significant improvements of total AIS grade (RR: 3.70; P < 0.001), AIS grade A (RR: 3.57; P < 0.001), ASIA sensory score (OR: 8.63; P < 0.001) and reduction of residual urine volume (OR: -36.37; P = 0.03) were observed in experimental group compared with control group. However, no significant differences of motor score (OR: 1.37, P = 0.19) and ADL score (OR: 2.61, P = 0.27) were observed between experimental and control groups. In addition, there were no serious and permanent adverse effects after cell transplantation. Cell transplantation with MSCs is effective and safe in improving the sensory and bladder functions of SCI patients.
Topics: Cell Transplantation; Mesenchymal Stem Cell Transplantation; Spinal Cord Injuries; Treatment Outcome
PubMed: 30362373
DOI: 10.1177/0963689718808471 -
Regenerative Medicine 2015Stem cell therapies have been explored as a new avenue for the treatment of neurologic disease and damage within the CNS in part due to their native ability to mimic... (Review)
Review
Stem cell therapies have been explored as a new avenue for the treatment of neurologic disease and damage within the CNS in part due to their native ability to mimic repair mechanisms in the brain. Mesenchymal stem cells have been of particular clinical interest due to their ability to release beneficial neurotrophic factors and their ability to foster a neuroprotective microenviroment. While early stem cell transplantation therapies have been fraught with technical and political concerns as well as limited clinical benefits, mesenchymal stem cell therapies have been shown to be clinically beneficial and derivable from nonembryonic, adult sources. The focus of this review will be on emerging and extant stem cell therapies for juvenile and adult-onset Huntington's disease.
Topics: Adult; Animals; Animals, Genetically Modified; Cell Differentiation; Cell Transplantation; Central Nervous System; Child; Clinical Trials as Topic; Disease Progression; Embryonic Stem Cells; Humans; Huntington Disease; Immune System; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Nerve Growth Factors; Neurons; Neuroprotection; Stem Cell Transplantation
PubMed: 26237705
DOI: 10.2217/rme.15.25 -
Frontiers in Immunology 2023Umbilical cord blood transplantation (UCBT) and peripheral blood stem cell transplantation (PBSCT) are effective allogeneic treatments for patients with malignant and...
Umbilical cord blood transplantation (UCBT) and peripheral blood stem cell transplantation (PBSCT) are effective allogeneic treatments for patients with malignant and non-malignant refractory hematological diseases. However, the differences in the immune cell reconstitution and the immune reactions during initial stages post-transplantation are not well established between UCBT and PBSCT. Therefore, in this study, we analyzed the differences in the immune reactions during the early stages (days 7-100 post-transplantation) such as pre-engraftment syndrome (PES), engraftment syndrome (ES), and acute graft-versus-host disease (aGVHD) and the immune cell reconstitution between the UCBT and the PBSCT group of patients. We enrolled a cohort of patients that underwent UCBT or PBSCT and healthy controls (n=25 each) and evaluated their peripheral blood mononuclear cell (PBMC) samples and plasma cytokine (IL-10 and GM-CSF) levels using flow cytometry and ELISA, respectively. Our results showed that the incidences of early immune reactions such as PES, ES, and aGVHD were significantly higher in the UCBT group compared to the PBSCT group. Furthermore, in comparison with the PBSCT group, the UCBT group showed higher proportion and numbers of naïve CD4 T cells, lower proportion and numbers of Tregs, higher proportion of CD8 T cells with increased activity, and higher proportion of mature CD56 CD16 NK cells during the early stages post-transplantation. Moreover, the plasma levels of GM-CSF were significantly higher in the UCBT group compared to the PBSCT group in the third week after transplantation. Overall, our findings demonstrated significant differences in the post-transplantation immune cell reconstitution between the UCBT and the PBSCT group of patients. These characteristics were associated with significant differences between the UCBT and the PBSCT groups regarding the incidences of immune reactions during the early stages post transplantation.
Topics: Humans; Peripheral Blood Stem Cell Transplantation; Granulocyte-Macrophage Colony-Stimulating Factor; Leukocytes, Mononuclear; CD8-Positive T-Lymphocytes; Cord Blood Stem Cell Transplantation; Hematopoietic Stem Cell Transplantation; Graft vs Host Disease
PubMed: 37114055
DOI: 10.3389/fimmu.2023.1084901 -
International Journal of Molecular... May 2017Mesenchymal stem cells (MSCs) are a heterogeneous cellular population containing different progenitors able to repair tissues, support hematopoiesis, and modulate immune... (Review)
Review
Mesenchymal stem cells (MSCs) are a heterogeneous cellular population containing different progenitors able to repair tissues, support hematopoiesis, and modulate immune and inflammatory responses. Several clinical trials have used MSCs in allogeneic hematopoietic stem cell transplantation (allo-HSCT) to prevent hematopoietic stem cell (HSC) engraftment failure, reduce aplasia post chemotherapy, and to control graft versus host disease (GvHD). The efficacy of MSCs is linked to their immune suppressive and anti-inflammatory properties primarily due to the release of soluble factors. Recent studies indicate that most of these effects are mediated by extracellular vesicles (EVs). MSC-EVs have therefore therapeutic effects in regenerative medicine, tumor inhibition, and immune-regulation. MSC-EVs may offer specific advantages for patient safety, such as lower propensity to trigger innate and adaptive immune responses. It has been also shown that MSC-EVs can prevent or treat acute-GvHD by modulating the immune-response and, combined with HSCs, may contribute to the hematopoietic microenvironment reconstitution. Finally, MSC-EVs may provide a new potential therapeutic option (e.g., transplantation, gene therapy) for different diseases, particularly hematological malignancies. In this review, we will describe MSC and MSC-EVs role in improving allo-HSCT procedures and in treating GvHD.
Topics: Animals; Extracellular Vesicles; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells
PubMed: 28486431
DOI: 10.3390/ijms18051022 -
Bone Marrow Transplantation Mar 2020Allogeneic stem cell transplantation (alloSCT) is an effective immunotherapy in patients with hematological malignancies. Endothelial dysfunction was linked to major...
Allogeneic stem cell transplantation (alloSCT) is an effective immunotherapy in patients with hematological malignancies. Endothelial dysfunction was linked to major complications after alloSCT. We asked the question if the "Endothelial Activation and Stress Index" (EASIX; [(creatinine × LDH) ÷ thrombocytes]) can predict mortality after alloSCT. We performed a retrospective cohort analysis in five alloSCT centers in the USA and Germany. EASIX was assessed prior to conditioning (EASIX-pre) and correlated with mortality in 755 patients of a training cohort in multivariable models. The predictive model established in the training cohort was validated in 1267 adult allo-recipients. Increasing EASIX-pre predicted lower overall survival (OS) after alloSCT, and successful model validation was achieved for the validation cohort. We found that EASIX-pre predicts OS irrespective of established scores. Moreover, EASIX-pre was also a significant prognostic factor for transplant-associated microangiopathy. Finally, EASIX-pre correlated with biomarkers of endothelial homeostasis such as CXCL8, interleukin-18, and insulin-like-growth-factor-1 serum levels. This study establishes EASIX-pre based on a standard laboratory biomarker panel as a predictor of individual risk of mortality after alloSCT independently from established clinical criteria.
Topics: Adult; Germany; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Retrospective Studies; Stem Cell Transplantation; Transplantation Conditioning; Transplantation, Homologous
PubMed: 31558788
DOI: 10.1038/s41409-019-0703-1 -
Circulation Research Jul 2018Given the rising prevalence of cardiovascular disease worldwide and the limited therapeutic options for severe heart failure, novel technologies that harness the... (Review)
Review
Given the rising prevalence of cardiovascular disease worldwide and the limited therapeutic options for severe heart failure, novel technologies that harness the regenerative capacity of the heart are sorely needed. The therapeutic use of stem cells has the potential to reverse myocardial injury and improve cardiac function, in contrast to most current medical therapies that only mitigate heart failure symptoms. Nearly 2 decades and >200 trials for cardiovascular disease have revealed that most cell types are safe; however, their efficacy remains controversial, limiting the transition of this therapy from investigation to practice. Lessons learned from these initial studies are driving the design of new clinical trials; higher fidelity of cell isolation techniques, standardization of conditions, more consistent use of state of the art measurement techniques, and assessment of multiple end points to garner insights into the efficacy of stem cells. Translation to clinical trials has almost outpaced our mechanistic understanding, and individual patient factors likely play a large role in stem cell efficacy. Therefore, careful analysis of dosing, delivery methods, and the ideal patient populations is necessary to translate cell therapy from research to practice. We are at a pivotal stage in the field in which information from many relatively small clinical trials must guide carefully executed efficacy trials. Larger efficacy trials are being launched to answer questions about older, first-generation stem cell therapeutics, while novel, second-generation products are being introduced into the clinical realm. This review critically examines the current state of clinical research on cell-based therapies for cardiovascular disease, highlighting the controversies in the field, improvements in clinical trial design, and the application of exciting new cell products.
Topics: Cardiovascular Diseases; Clinical Trials as Topic; Humans; Regenerative Medicine; Stem Cell Transplantation
PubMed: 29976692
DOI: 10.1161/CIRCRESAHA.118.311217 -
Molecular Neurodegeneration Nov 2017Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative condition where loss of motor neurons within the brain and spinal cord leads to muscle... (Review)
Review
Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative condition where loss of motor neurons within the brain and spinal cord leads to muscle atrophy, weakness, paralysis and ultimately death within 3-5 years from onset of symptoms. The specific molecular mechanisms underlying the disease pathology are not fully understood and neuroprotective treatment options are minimally effective. In recent years, stem cell transplantation as a new therapy for ALS patients has been extensively investigated, becoming an intense and debated field of study. In several preclinical studies using the SOD1 mouse model of ALS, stem cells were demonstrated to be neuroprotective, effectively delayed disease onset and extended survival. Despite substantial improvements in stem cell technology and promising results in preclinical studies, several questions still remain unanswered, such as the identification of the most suitable and beneficial cell source, cell dose, route of delivery and therapeutic mechanisms. This review will cover publications in this field and comprehensively discuss advances, challenges and future direction regarding the therapeutic potential of stem cells in ALS, with a focus on mesenchymal stem cells. In summary, given their high proliferation activity, immunomodulation, multi-differentiation potential, and the capacity to secrete neuroprotective factors, adult mesenchymal stem cells represent a promising candidate for clinical translation. However, technical hurdles such as optimal dose, differentiation state, route of administration, and the underlying potential therapeutic mechanisms still need to be assessed.
Topics: Amyotrophic Lateral Sclerosis; Animals; Humans; Stem Cell Transplantation
PubMed: 29132389
DOI: 10.1186/s13024-017-0227-3 -
Tissue Engineering. Part B, Reviews Apr 2010The face distinguishes one human being from another. When the face is disfigured because of trauma, tumor removal, congenital anomalies, or chronic diseases, the patient... (Review)
Review
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.
Topics: Animals; Cell Movement; Cell Transplantation; Face; Facial Transplantation; Humans; Models, Biological; Plastic Surgery Procedures
PubMed: 19891541
DOI: 10.1089/ten.TEB.2009.0496 -
Biology of Blood and Marrow... Jan 2017Continual advances in hematopoietic cell transplantation (HCT) have greatly improved early transplantation-related mortality and broadened the applicability of this...
Continual advances in hematopoietic cell transplantation (HCT) have greatly improved early transplantation-related mortality and broadened the applicability of this intense but curative therapy. With growing success there is increasing awareness of late complications, occurring ≥1 year after treatment, and their associated morbidity and mortality in HCT survivors. These late effects occur with a wide spectrum in terms of latency, intensity, reversibility, and lethality. There is a need to understand the biology, surveillance, management, and patient experience of HCT-related effects, as well as the health care and research infrastructure to manage this growing population. To address these needs, the National Cancer Institute and National Heart, Lung and Blood Institute cosponsored a 12-month initiative to identify barriers and knowledge gaps and to formulate research and practice recommendations. Six major areas of interest were identified: research methodology and study design, subsequent neoplasms, patient-centered outcomes, immune dysregulation and pathobiology, cardiovascular disease and associated risk factors, and health care delivery. These findings were presented during the 2016 workshop and revised based on public response. This report provides an overview of the National Institutes of Health HCT Late Effects Initiative process and recommendations.
Topics: Delivery of Health Care; Health Planning Guidelines; Hematopoietic Stem Cell Transplantation; Humans; Long Term Adverse Effects; National Cancer Institute (U.S.); National Heart, Lung, and Blood Institute (U.S.); National Institutes of Health (U.S.); Research Design; Time Factors; United States
PubMed: 27989931
DOI: 10.1016/j.bbmt.2016.10.020