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Cells Jul 2019Mesenchymal stem cells (MSCs) are multilineage cells with the ability to self-renew and differentiate into a variety of cell types, which play key roles in tissue... (Review)
Review
Mesenchymal stem cells (MSCs) are multilineage cells with the ability to self-renew and differentiate into a variety of cell types, which play key roles in tissue healing and regenerative medicine. Bone marrow-derived mesenchymal stem cells (BMSCs) are the most frequently used stem cells in cell therapy and tissue engineering. However, it is prerequisite for BMSCs to mobilize from bone marrow and migrate into injured tissues during the healing process, through peripheral circulation. The migration of BMSCs is regulated by mechanical and chemical factors in this trafficking process. In this paper, we review the effects of several main regulatory factors on BMSC migration and its underlying mechanism; discuss two critical roles of BMSCs-namely, directed differentiation and the paracrine function-in tissue repair; and provide insight into the relationship between BMSC migration and tissue repair, which may provide a better guide for clinical applications in tissue repair through the efficient regulation of BMSC migration.
Topics: Animals; Cell Differentiation; Cell Movement; Humans; Mesenchymal Stem Cells; Regeneration; Transcription Factors; Wound Healing
PubMed: 31357692
DOI: 10.3390/cells8080784 -
Cell Stem Cell Jun 2018Mesenchymal stromal cells (MSCs) have been the subject of clinical trials for more than a generation, and the outcomes of advanced clinical trials have fallen short of... (Review)
Review
Mesenchymal stromal cells (MSCs) have been the subject of clinical trials for more than a generation, and the outcomes of advanced clinical trials have fallen short of expectations raised by encouraging pre-clinical animal data in a wide array of disease models. In this Perspective, important biological and pharmacological disparities in pre-clinical research and human translational studies are highlighted, and analyses of clinical trial failures and recent successes provide a rational pathway to MSC regulatory approval and deployment for disorders with unmet medical needs.
Topics: Animals; Graft vs Host Disease; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells
PubMed: 29859173
DOI: 10.1016/j.stem.2018.05.004 -
Stem Cell Research & Therapy Mar 2018Mesenchymal stem cells (MSCs) are multipotent stem cells that have gained significant attention in the field of regenerative medicine. The differentiation potential... (Review)
Review
Mesenchymal stem cells (MSCs) are multipotent stem cells that have gained significant attention in the field of regenerative medicine. The differentiation potential along with paracrine properties of MSCs have made them a key option for tissue repair. The paracrine functions of MSCs are applied through secreting soluble factors and releasing extracellular vesicles like exosomes and microvesicles. Extracellular vesicles are predominantly endosomal in origin and contain a cargo of miRNA, mRNA, and proteins that are transferred from their original cells to target cells. Recently it has emerged that extracellular vesicles alone are responsible for the therapeutic effect of MSCs in plenty of animal diseases models. Hence, MSC-derived extracellular vesicles may be used as an alternative MSC-based therapy in regenerative medicine. In this review we discuss MSC-derived extracellular vesicles and their therapeutic potential in various diseases.
Topics: Animals; Extracellular Vesicles; Humans; Mesenchymal Stem Cells; Paracrine Communication; Regenerative Medicine
PubMed: 29523213
DOI: 10.1186/s13287-018-0791-7 -
Cell Reports Mar 2018Fibroblast heterogeneity has long been recognized in mouse and human lungs, homeostasis, and disease states. However, there is no common consensus on fibroblast...
Fibroblast heterogeneity has long been recognized in mouse and human lungs, homeostasis, and disease states. However, there is no common consensus on fibroblast subtypes, lineages, biological properties, signaling, and plasticity, which severely hampers our understanding of the mechanisms of fibrosis. To comprehensively classify fibroblast populations in the lung using an unbiased approach, single-cell RNA sequencing was performed with mesenchymal preparations from either uninjured or bleomycin-treated mouse lungs. Single-cell transcriptome analyses classified and defined six mesenchymal cell types in normal lung and seven in fibrotic lung. Furthermore, delineation of their differentiation trajectory was achieved by a machine learning method. This collection of single-cell transcriptomes and the distinct classification of fibroblast subsets provide a new resource for understanding the fibroblast landscape and the roles of fibroblasts in fibrotic diseases.
Topics: Animals; Cell Differentiation; Cells, Cultured; Disease Models, Animal; Fibroblasts; Mesenchymal Stem Cells; Mice; Mice, Inbred C57BL; Pulmonary Fibrosis; Single-Cell Analysis
PubMed: 29590628
DOI: 10.1016/j.celrep.2018.03.010 -
Cell Transplantation 2015The human umbilical cord is a promising source of mesenchymal stem cells (HUCMSCs). Unlike bone marrow stem cells, HUCMSCs have a painless collection procedure and... (Review)
Review
The human umbilical cord is a promising source of mesenchymal stem cells (HUCMSCs). Unlike bone marrow stem cells, HUCMSCs have a painless collection procedure and faster self-renewal properties. Different derivation protocols may provide different amounts and populations of stem cells. Stem cell populations have also been reported in other compartments of the umbilical cord, such as the cord lining, perivascular tissue, and Wharton's jelly. HUCMSCs are noncontroversial sources compared to embryonic stem cells. They can differentiate into the three germ layers that promote tissue repair and modulate immune responses and anticancer properties. Thus, they are attractive autologous or allogenic agents for the treatment of malignant and nonmalignant solid and soft cancers. HUCMCs also can be the feeder layer for embryonic stem cells or other pluripotent stem cells. Regarding their therapeutic value, storage banking system and protocols should be established immediately. This review critically evaluates their therapeutic value, challenges, and future directions for their clinical applications.
Topics: Animals; Biomarkers; Cell Differentiation; Cell- and Tissue-Based Therapy; Disease Models, Animal; Humans; Immunomodulation; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Neoplasms; Umbilical Cord
PubMed: 25622293
DOI: 10.3727/096368915X686841 -
Stem Cells Translational Medicine Dec 2017Mesenchymal stem cells (MSC) hold great potential for regenerative medicine because of their ability for self-renewal and differentiation into tissue-specific cells such... (Review)
Review
Mesenchymal stem cells (MSC) hold great potential for regenerative medicine because of their ability for self-renewal and differentiation into tissue-specific cells such as osteoblasts, chondrocytes, and adipocytes. MSCs orchestrate tissue development, maintenance and repair, and are useful for musculoskeletal regenerative therapies to treat age-related orthopedic degenerative diseases and other clinical conditions. Importantly, MSCs produce secretory factors that play critical roles in tissue repair that support both engraftment and trophic functions (autocrine and paracrine). The development of uniform protocols for both preparation and characterization of MSCs, including standardized functional assays for evaluation of their biological potential, are critical factors contributing to their clinical utility. Quality control and release criteria for MSCs should include cell surface markers, differentiation potential, and other essential cell parameters. For example, cell surface marker profiles (surfactome), bone-forming capacities in ectopic and orthotopic models, as well as cell size and granularity, telomere length, senescence status, trophic factor secretion (secretome), and immunomodulation, should be thoroughly assessed to predict MSC utility for regenerative medicine. We propose that these and other functionalities of MSCs should be characterized prior to use in clinical applications as part of comprehensive and uniform guidelines and release criteria for their clinical-grade production to achieve predictably favorable treatment outcomes for stem cell therapy. Stem Cells Translational Medicine 2017;6:2173-2185.
Topics: Cell Differentiation; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Regenerative Medicine
PubMed: 29076267
DOI: 10.1002/sctm.17-0129 -
Stem Cells (Dayton, Ohio) Apr 2017Mesenchymal stem cell transplantation is undergoing extensive evaluation as a cellular therapy in human clinical trials. Because MSCs are easily isolated and amenable to... (Review)
Review
Mesenchymal stem cell transplantation is undergoing extensive evaluation as a cellular therapy in human clinical trials. Because MSCs are easily isolated and amenable to culture expansion in vitro there is a natural desire to test MSCs in many diverse clinical indications. This is exemplified by the rapidly expanding literature base that includes many in vivo animal models. More recently, MSC-derived extracellular vesicles (EVs), which include exosomes and microvesicles (MV), are being examined for their role in MSC-based cellular therapy. These vesicles are involved in cell-to-cell communication, cell signaling, and altering cell or tissue metabolism at short or long distances in the body. The exosomes and MVs can influence tissue responses to injury, infection, and disease. MSC-derived exosomes have a content that includes cytokines and growth factors, signaling lipids, mRNAs, and regulatory miRNAs. To the extent that MSC exosomes can be used for cell-free regenerative medicine, much will depend on the quality, reproducibility, and potency of their production, in the same manner that these parameters dictate the development of cell-based MSC therapies. However, the MSC exosome's contents are not static, but rather a product of the MSC tissue origin, its activities and the immediate intercellular neighbors of the MSCs. As such, the exosome content produced by MSCs appears to be altered when MSCs are cultured with tumor cells or in the in vivo tumor microenvironment. Therefore, careful attention to detail in producing MSC exosomes may provide a new therapeutic paradigm for cell-free MSC-based therapies with decreased risk. Stem Cells 2017;35:851-858.
Topics: Animals; Exosomes; Humans; Mesenchymal Stem Cells; Paracrine Communication; Stem Cell Niche; Wound Healing
PubMed: 28294454
DOI: 10.1002/stem.2575 -
Experimental & Molecular Medicine Jun 2017The administration of mesenchymal stem cells (MSCs) as a therapy for liver disease holds great promise. MSCs can differentiate into hepatocytes, reduce liver... (Review)
Review
The administration of mesenchymal stem cells (MSCs) as a therapy for liver disease holds great promise. MSCs can differentiate into hepatocytes, reduce liver inflammation, promote hepatic regeneration and secrete protective cytokines. However, the risks of iatrogenic tumor formation, cellular rejection and infusional toxicity in MSC transplantation remain unresolved. Accumulating evidence now suggests that a novel cell-free therapy, MSC-secreted exosomes, might constitute a compelling alternative because of their advantages over the corresponding MSCs. They are smaller and less complex than their parent cells and, thus, easier to produce and store, they are devoid of viable cells, and they present no risk of tumor formation. Moreover, they are less immunogenic than their parent cells because of their lower content in membrane-bound proteins. This paper reviews the biogenesis of MSC exosomes and their physiological functions, and highlights the specific biochemical potential of MSC-derived exosomes in restoring tissue homeostasis. In addition, we summarize the recent advances in the role of exosomes in MSC therapy for various liver diseases, including liver fibrosis, acute liver injury and hepatocellular carcinoma. This paper also discusses the potential challenges and strategies in the use of exosome-based therapies for liver disease in the future.
Topics: Animals; Exosomes; Humans; Liver Diseases; Mesenchymal Stem Cells; Mice; Rats
PubMed: 28620221
DOI: 10.1038/emm.2017.63 -
Physiology (Bethesda, Md.) Mar 2020Adipose-derived stem cells (ASCs) can self-renew and differentiate along multiple cell lineages. ASCs are also potently anti-inflammatory due to their inherent ability... (Review)
Review
Adipose-derived stem cells (ASCs) can self-renew and differentiate along multiple cell lineages. ASCs are also potently anti-inflammatory due to their inherent ability to regulate the immune system by secreting anti-inflammatory cytokines and growth factors that play a crucial role in the pathology of many diseases, including multiple sclerosis, diabetes mellitus, Crohn's, SLE, and graft-versus-host disease. The immunomodulatory effects and mechanisms of action of ASCs on pathological conditions are reviewed here.
Topics: Adipose Tissue; Animals; Cell Differentiation; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Stem Cells
PubMed: 32027561
DOI: 10.1152/physiol.00021.2019 -
Advances in Experimental Medicine and... 2019Bone marrow environments are composed of multiple cell types, most of which are thought to be derived from mesenchymal stem cells. In mouse bone marrow, stromal cells... (Review)
Review
Bone marrow environments are composed of multiple cell types, most of which are thought to be derived from mesenchymal stem cells. In mouse bone marrow, stromal cells with CD45 Tie2 CD90 CD51 CD105 phenotype, Nestin-GFP, CXCL12-abundant reticular (CAR) cells, PDGFRα Sca-1 or CD51 PDGFRα, and Prx-1-derived CD45 Ter119 PDGFRα Sca-1 populations select for MSC activity. There is evidence that these stromal cell populations display some significant overlap with each other and comprise important cellular constituents of the hematopoietic stem cell niche. Moreover, these mesenchymal cell populations share characteristics in their location as they all are found around bone marrow vessels (can be called "pericytes"). In this chapter, with reviewing the recent literatures, how the pericytes relate to physiological and pathological hematopoiesis is argued.
Topics: Animals; Bone Marrow; Bone Marrow Cells; Hematopoiesis; Humans; Mesenchymal Stem Cells; Mice; Pericytes; Stem Cell Niche
PubMed: 30937865
DOI: 10.1007/978-3-030-11093-2_6