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Biochimica Et Biophysica Acta.... Apr 2020What is clear is we are in the era of the stem cell and its potential in ameliorating human disease. Our perspective is generated from an in vivo model in a large animal... (Review)
Review
What is clear is we are in the era of the stem cell and its potential in ameliorating human disease. Our perspective is generated from an in vivo model in a large animal that offers significant advantages (complete transplantation tolerance, large size and long life span). This review is an effort to meld our preclinical observations with others for the reader and to outline potential avenues to improve the present outlook for patients with diabetes. This effort exams the history or background of stem cell research in the laboratory and the clinic, types of stem cells, pluripotency or lack thereof based on a variety of pre-clinical investigations attempting endocrine pancreas recovery using stem cell transplantation. The focus is on the use of hematopoietic and mesenchymal stem cells. This review will also examine recent clinical experience following stem cell transplantation in patients with type 1 diabetes.
Topics: Animals; Diabetes Mellitus, Type 1; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells
PubMed: 30508575
DOI: 10.1016/j.bbadis.2018.10.033 -
Cells May 2020The pleiotropic behavior of mesenchymal stem cells (MSCs) has gained global attention due to their immense potential for immunosuppression and their therapeutic role in... (Review)
Review
The pleiotropic behavior of mesenchymal stem cells (MSCs) has gained global attention due to their immense potential for immunosuppression and their therapeutic role in immune disorders. MSCs migrate towards inflamed microenvironments, produce anti-inflammatory cytokines and conceal themselves from the innate immune system. These signatures are the reason for the uprising in the sciences of cellular therapy in the last decades. Irrespective of their therapeutic role in immune disorders, some factors limit beneficial effects such as inconsistency of cell characteristics, erratic protocols, deviating dosages, and diverse transfusion patterns. Conclusive protocols for cell culture, differentiation, expansion, and cryopreservation of MSCs are of the utmost importance for a better understanding of MSCs in therapeutic applications. In this review, we address the immunomodulatory properties and immunosuppressive actions of MSCs. Also, we sum up the results of the enhancement, utilization, and therapeutic responses of MSCs in treating inflammatory diseases, metabolic disorders and diabetes.
Topics: Adipocytes; Clinical Trials as Topic; Diabetes Mellitus; Humans; Immune Evasion; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells
PubMed: 32384763
DOI: 10.3390/cells9051145 -
International Journal of Biological... 2020The liver is sensitive to pathogen-induced acute or chronic liver injury, and liver transplantation (LT) is the only effective strategy for end-stage liver diseases.... (Review)
Review
The liver is sensitive to pathogen-induced acute or chronic liver injury, and liver transplantation (LT) is the only effective strategy for end-stage liver diseases. However, the clinical application is limited by a shortage of liver organs, immunological rejection and high cost. Mesenchymal stromal cell (MSC)-based therapy has gradually become a hot topic for promoting liver regeneration and repairing liver injury in various liver diseases, since MSCs are reported to migrate toward injured tissues, undergo hepatogenic differentiation, inhibit inflammatory factor release and enhance the proliferation of liver cells . MSCs exert immunoregulatory effects through cell-cell contact and the secretion of anti-inflammatory factors to inhibit liver inflammation and promote liver regeneration. In addition, MSCs are reported to effectively inhibit the activation of cells of the innate immune system, including macrophages, natural killer (NK) cells, dendritic cells (DCs), monocytes and other immune cells, and inhibit the activation of cells of the adaptive immune system, including T lymphocytes, B lymphocytes and subsets of T cells or B cells. In the current review, we mainly focus on the potential effects and mechanisms of MSCs in inhibiting the activation of immune cells to attenuate liver injury in models or patients with acute liver failure (ALF), nonalcoholic fatty liver disease (NAFLD), and liver fibrosis and in patients or models after LT. We highlight that MSC transplantation may replace general therapies for eliminating acute or chronic liver injury in the near future.
Topics: Animals; Humans; Liver; Liver Regeneration; Liver Transplantation; Mesenchymal Stem Cells
PubMed: 32071558
DOI: 10.7150/ijbs.39725 -
International Journal of Molecular... Jan 2021Tissue engineering has been an inveterate area in the field of regenerative medicine for several decades. However, there remains limitations to engineer and regenerate... (Review)
Review
Tissue engineering has been an inveterate area in the field of regenerative medicine for several decades. However, there remains limitations to engineer and regenerate tissues. Targeted therapies using cell-encapsulated hydrogels, such as mesenchymal stem cells (MSCs), are capable of reducing inflammation and increasing the regenerative potential in several tissues. In addition, the use of MSC-derived nano-scale secretions (i.e., exosomes) has been promising. Exosomes originate from the multivesicular division of cells and have high therapeutic potential, yet neither self-replicate nor cause auto-immune reactions to the host. To maintain their biological activity and allow a controlled release, these paracrine factors can be encapsulated in biomaterials. Among the different types of biomaterials in which exosome infusion is exploited, hydrogels have proven to be the most user-friendly, economical, and accessible material. In this paper, we highlight the importance of MSCs and MSC-derived exosomes in tissue engineering and the different biomaterial strategies used in fabricating exosome-based biomaterials, to facilitate hard and soft tissue engineering.
Topics: Animals; Biocompatible Materials; Cell Differentiation; Drug Carriers; Drug Compounding; Drug Delivery Systems; Exosomes; Humans; Hydrogels; Mesenchymal Stem Cells; Osteogenesis; Regenerative Medicine; Tissue Engineering
PubMed: 33445616
DOI: 10.3390/ijms22020684 -
Frontiers in Immunology 2021Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Although previous studies have demonstrated that SLE is related to the imbalance of cells in the... (Review)
Review
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Although previous studies have demonstrated that SLE is related to the imbalance of cells in the immune system, including B cells, T cells, and dendritic cells, etc., the mechanisms underlying SLE pathogenesis remain unclear. Therefore, effective and low side-effect therapies for SLE are lacking. Recently, mesenchymal stem cell (MSC) therapy for autoimmune diseases, particularly SLE, has gained increasing attention. This therapy can improve the signs and symptoms of refractory SLE by promoting the proliferation of Th2 and Treg cells and inhibiting the activity of Th1, Th17, and B cells, etc. However, MSC therapy is also reported ineffective in some patients with SLE, which may be related to MSC- or patient-derived factors. Therefore, the therapeutic effects of MSCs should be further confirmed. This review summarizes the status of MSC therapy in refractory SLE treatment and potential reasons for the ineffectiveness of MSC therapy from three perspectives. We propose various MSC modification methods that may be beneficial in enhancing the immunosuppression of MSCs in SLE. However, their safety and protective effects in patients with SLE still need to be confirmed by further experimental and clinical evidence.
Topics: Adaptive Immunity; Animals; Cellular Microenvironment; Humans; Immune Tolerance; Immunity, Innate; Lupus Erythematosus, Systemic; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Phenotype; Treatment Outcome
PubMed: 34659214
DOI: 10.3389/fimmu.2021.728190 -
International Journal of Molecular... Nov 2021The therapeutic potential of the dental pulp stem (DSC) cell-derived secretome, consisting of various biomolecules, is undergoing intense research. Despite promising in... (Review)
Review
The therapeutic potential of the dental pulp stem (DSC) cell-derived secretome, consisting of various biomolecules, is undergoing intense research. Despite promising in vitro and in vivo studies, most DSC secretome-based therapies have not been implemented in human medicine because the paracrine effect of the bioactive factors secreted by human dental pulp stem cells (hDPSCs) and human exfoliated deciduous teeth (SHEDs) is not completely understood. In this review, we outline the current data on the hDPSC- and SHED-derived secretome as a potential candidate in the regeneration of bone, cartilage, and nerve tissue. Published reports demonstrate that the dental MSC-derived secretome/conditional medium may be effective in treating neurodegenerative diseases, neural injuries, cartilage defects, and repairing bone by regulating neuroprotective, anti-inflammatory, antiapoptotic, and angiogenic processes through secretome paracrine mechanisms. Dental MSC-secretomes, similarly to the bone marrow MSC-secretome activate molecular and cellular mechanisms, which determine the effectiveness of cell-free therapy. Many reports emphasize that dental MSC-derived secretomes have potential application in tissue-regenerating therapy due to their multidirectional paracrine effect observed in the therapy of many different injured tissues.
Topics: Dental Pulp; Humans; Mesenchymal Stem Cells; Neurodegenerative Diseases; Regenerative Medicine; Secretome; Stem Cells
PubMed: 34769446
DOI: 10.3390/ijms222112018 -
Journal of Hematology & Oncology Feb 2021Mesenchymal stromal cells (MSCs), also known as mesenchymal stem cells, have been intensely investigated for clinical applications within the last decades. However, the... (Review)
Review
Mesenchymal stromal cells (MSCs), also known as mesenchymal stem cells, have been intensely investigated for clinical applications within the last decades. However, the majority of registered clinical trials applying MSC therapy for diverse human diseases have fallen short of expectations, despite the encouraging pre-clinical outcomes in varied animal disease models. This can be attributable to inconsistent criteria for MSCs identity across studies and their inherited heterogeneity. Nowadays, with the emergence of advanced biological techniques and substantial improvements in bio-engineered materials, strategies have been developed to overcome clinical challenges in MSC application. Here in this review, we will discuss the major challenges of MSC therapies in clinical application, the factors impacting the diversity of MSCs, the potential approaches that modify MSC products with the highest therapeutic potential, and finally the usage of MSCs for COVID-19 pandemic disease.
Topics: Animals; Artificial Intelligence; COVID-19; CRISPR-Cas Systems; Cell Differentiation; Cell Movement; Clinical Trials as Topic; Extracellular Vesicles; Genetic Engineering; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells
PubMed: 33579329
DOI: 10.1186/s13045-021-01037-x -
Stem Cell Reviews and Reports Jun 2022Human mesenchymal stem cells (MSCs), also known as mesenchymal stromal cells or medicinal signaling cells, are important adult stem cells for regenerative medicine,... (Review)
Review
Human mesenchymal stem cells (MSCs), also known as mesenchymal stromal cells or medicinal signaling cells, are important adult stem cells for regenerative medicine, largely due to their regenerative characteristics such as self-renewal, secretion of trophic factors, and the capability of inducing mesenchymal cell lineages. MSCs also possess homing and trophic properties modulating immune system, influencing microenvironment around damaged tissues and enhancing tissue repair, thus offering a broad perspective in cell-based therapies. Therefore, it is not surprising that MSCs have been the broadly used adult stem cells in clinical trials. To gain better insights into the current applications of MSCs in clinical applications, we perform a comprehensive review of reported data of MSCs clinical trials conducted globally. We summarize the biological effects and mechanisms of action of MSCs, elucidating recent clinical trials phases and findings, highlighting therapeutic effects of MSCs in several representative diseases, including neurological, musculoskeletal diseases and most recent Coronavirus infectious disease. Finally, we also highlight the challenges faced by many clinical trials and propose potential solutions to streamline the use of MSCs in routine clinical applications and regenerative medicine.
Topics: Adult; Adult Stem Cells; Cell- and Tissue-Based Therapy; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Regenerative Medicine
PubMed: 35344199
DOI: 10.1007/s12015-022-10369-1 -
Stem Cells Translational Medicine Sep 2021Mesenchymal stem cell therapy (MSCT) for immune and inflammatory diseases continues to be popular based on progressive accumulation of preclinical mechanistic evidence.... (Review)
Review
Mesenchymal stem cell therapy (MSCT) for immune and inflammatory diseases continues to be popular based on progressive accumulation of preclinical mechanistic evidence. This has led to further expansion in clinical indications from graft rejection, autoimmune diseases, and osteoarthritis, to inflammatory liver and pulmonary diseases including COVID-19. A clear trend is the shift from using autologous to allogeneic MSCs, which can be immediately available as off-the-shelf products. In addition, new products such as cell-free exosomes and human pluripotent stem cell (hPSC)-derived MSCs are exciting developments to further prevalent use. Increasing numbers of trials have now published results in which safety of MSCT has been largely demonstrated. While reports of therapeutic endpoints are still emerging, efficacy can be seen for specific indications-including graft-vs-host-disease, strongly Th17-mediated autoimmune diseases, and osteoarthritis-which are more robustly supported by mechanistic preclinical evidence. In this review, we update and discuss outcomes in current MSCT clinical trials for immune and inflammatory disease, as well as new innovation and emerging trends in the field.
Topics: COVID-19; Graft vs Host Disease; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Pluripotent Stem Cells; SARS-CoV-2
PubMed: 34008922
DOI: 10.1002/sctm.21-0021 -
Open Biology Dec 2021Skeletal muscle possesses a remarkable regenerative capacity that relies on the activity of muscle stem cells, also known as satellite cells. The presence of... (Review)
Review
Skeletal muscle possesses a remarkable regenerative capacity that relies on the activity of muscle stem cells, also known as satellite cells. The presence of non-myogenic cells also plays a key role in the coordination of skeletal muscle regeneration. Particularly, fibro-adipogenic progenitors (FAPs) emerged as master regulators of muscle stem cell function and skeletal muscle regeneration. This population of muscle resident mesenchymal stromal cells has been initially characterized based on its bi-potent ability to differentiate into fibroblasts or adipocytes. New technologies such as single-cell RNAseq revealed the cellular heterogeneity of FAPs and their complex regulatory network during muscle regeneration. In acute injury, FAPs rapidly enter the cell cycle and secrete trophic factors that support the myogenic activity of muscle stem cells. Conversely, deregulation of FAP cell activity is associated with the accumulation of fibrofatty tissue in pathological conditions such as muscular dystrophies and ageing. Considering their central role in skeletal muscle pathophysiology, the regulatory mechanisms of FAPs and their cellular and molecular crosstalk with muscle stem cells are highly investigated in the field. In this review, we summarize the current knowledge on FAP cell characteristics, heterogeneity and the cellular crosstalk during skeletal muscle homeostasis and regeneration. We further describe their role in muscular disorders, as well as different therapeutic strategies targeting these cells to restore muscle regeneration.
Topics: Adipogenesis; Animals; Cell Differentiation; Gene Regulatory Networks; Homeostasis; Humans; Mesenchymal Stem Cells; Muscle, Skeletal; Regeneration; Sequence Analysis, RNA; Single-Cell Analysis
PubMed: 34875199
DOI: 10.1098/rsob.210110