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Cell Transplantation 2011Stem cells have two features: the ability to differentiate along different lineages and the ability of self-renewal. Two major types of stem cells have been described,... (Review)
Review
Stem cells have two features: the ability to differentiate along different lineages and the ability of self-renewal. Two major types of stem cells have been described, namely, embryonic stem cells and adult stem cells. Embryonic stem cells (ESC) are obtained from the inner cell mass of the blastocyst and are associated with tumorigenesis, and the use of human ESCs involves ethical and legal considerations. The use of adult mesenchymal stem cells is less problematic with regard to these issues. Mesenchymal stem cells (MSCs) are stromal cells that have the ability to self-renew and also exhibit multilineage differentiation. MSCs can be isolated from a variety of tissues, such as umbilical cord, endometrial polyps, menses blood, bone marrow, adipose tissue, etc. This is because the ease of harvest and quantity obtained make these sources most practical for experimental and possible clinical applications. Recently, MSCs have been found in new sources, such as menstrual blood and endometrium. There are likely more sources of MSCs waiting to be discovered, and MSCs may be a good candidate for future experimental or clinical applications. One of the major challenges is to elucidate the mechanisms of differentiation, mobilization, and homing of MSCs, which are highly complex. The multipotent properties of MSCs make them an attractive choice for possible development of clinical applications. Future studies should explore the role of MSCs in differentiation, transplantation, and immune response in various diseases.
Topics: Cell Differentiation; Endometrium; Fallopian Tubes; Female; Fetal Blood; Humans; Ligaments, Articular; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells
PubMed: 21396235
DOI: 10.3727/096368910X -
Wiley Interdisciplinary Reviews.... 2009Adult stem cells with multi or unipotent differentiation potential are present in almost all tissues of adult organisms. The main function of these stem cells is to... (Review)
Review
Adult stem cells with multi or unipotent differentiation potential are present in almost all tissues of adult organisms. The main function of these stem cells is to support normal repair and rejuvenation of diseased and aging tissues. Mesenchymal stem cells (MSCs) isolated from the bone marrow have the potential to differentiate into multiple connective tissues. Advancements in understanding tissue specific differentiation of MSCs in conjunction with global genomic and proteomic profiling of MSCs have not only provided insights into their biology but also made MSC based clinical trials a reality for treating various debilitating diseases and genetic disorders. The emerging evidence that MSCs are immunosuppressive makes them an even more attractive candidate for regenerative medicine as rejections of transplants by the recipient could be a limiting step for moving the stem cells based therapies from "bedside to bed side." To a large extent the therapeutic potential of MSCs is attributed to their differentiation ability. The fate and commitment of MSCs are regulated by various instructive signals from their immediate vicinity or microenvironment, which comprises many biological molecules (soluble and insoluble) and biomechanical forces. These biochemical and biophysical factors play a pivotal role in determining the efficacy of MSC differentiation and their contribution to the repair process. In this review, we discuss the characteristics of MSCs, their differentiation potential toward different skeletal tissues (cartilage and bone), and their emerging role in regenerative medicine.
Topics: Cell Differentiation; Humans; Mesenchymal Stem Cells; Regenerative Medicine
PubMed: 20835984
DOI: 10.1002/wsbm.26 -
Tissue Engineering. Part B, Reviews Feb 2019Culture expansion of MSCs has detrimental effects on various cell characteristics and attributes (e.g., phenotypic changes and senescence), which, in addition to... (Review)
Review
Culture expansion of MSCs has detrimental effects on various cell characteristics and attributes (e.g., phenotypic changes and senescence), which, in addition to inherent interdonor variability, negatively impact the standardization and reproducibility of their therapeutic potential. The identification of innate distinct functional MSC subpopulations, as well as the description of ex vivo protocols aimed at maintaining phenotypes and enhancing specific functions have the potential to overcome these limitations. The incorporation of those approaches into cell-based therapy would significantly impact the field, as more reproducible clinical outcomes may be achieved.
Topics: Animals; Cell Differentiation; Cell Proliferation; Cell- and Tissue-Based Therapy; Cellular Senescence; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells
PubMed: 30165783
DOI: 10.1089/ten.TEB.2018.0118 -
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 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 -
Cell Stem Cell Mar 2015Mesenchymal stromal cells (MSCs) are heterogeneous and primitive cells discovered first in the bone marrow (BM). They have putative roles in maintaining tissue... (Review)
Review
Mesenchymal stromal cells (MSCs) are heterogeneous and primitive cells discovered first in the bone marrow (BM). They have putative roles in maintaining tissue homeostasis and are increasingly recognized as components of stem cell niches, which are best defined in the blood. The absence of in vivo MSC markers has limited our ability to track their behavior in vivo and draw comparisons with in vitro observations. Here we review the historical background of BM-MSCs, advances made in their prospective isolation, their developmental origin and contribution to maintaining subsets of hematopoietic cells, and how mesenchymal cells contribute to other stem cell niches.
Topics: Animals; Antigens, Differentiation; Bone Marrow Cells; Humans; Mesenchymal Stem Cells; Stem Cell Niche
PubMed: 25748931
DOI: 10.1016/j.stem.2015.02.019 -
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 -
Human Cell Jul 2020Mesenchymal stem cells (MSCs) possess the capabilities of self-renewal and multipotent differentiation. Firstly isolated from bone marrow, MSCs are subsequently... (Review)
Review
Mesenchymal stem cells (MSCs) possess the capabilities of self-renewal and multipotent differentiation. Firstly isolated from bone marrow, MSCs are subsequently identified from various post-natal tissue types. Based the differentiation into tissue-specific cells, MSCs were capable of replacing damaged and diseased tissues. In addition, MSCs have been demonstrated to possess important immunomodulatory properties. Increasing data showed that MSCs exhibited tropism for sites of the tumor microenvironment and interacted with tumor cells closely through paracrine signaling. Therefore, better understanding of crosstalk between MSCs and tumor cells will be able to develop potential strategies in the treatment of tumors in the future. Herein, we summarize the research progress of the influence of MSCs on tumor cells and the prospect of their application in tumor therapy in this review.
Topics: Bone Marrow Cells; Cell Communication; Cell Differentiation; Immunomodulation; Mesenchymal Stem Cells; Neoplasms; Tumor Microenvironment
PubMed: 32378164
DOI: 10.1007/s13577-020-00369-z -
Reviews in the Neurosciences Nov 2019Traumatic brain injury (TBI) is a major cause of injury-related mortality and morbidity in the USA and around the world. The survivors may suffer from cognitive and... (Review)
Review
Traumatic brain injury (TBI) is a major cause of injury-related mortality and morbidity in the USA and around the world. The survivors may suffer from cognitive and memory deficits, vision and hearing loss, movement disorders, and different psychological problems. The primary insult causes neuronal damage and activates astrocytes and microglia which evokes immune responses causing further damage to the brain. Clinical trials of drugs to recover the neuronal loss are not very successful. Regenerative approaches for TBI using mesenchymal stem cells (MSCs) seem promising. Results of preclinical research have shown that transplantation of MSCs reduced secondary neurodegeneration and neuroinflammation, promoted neurogenesis and angiogenesis, and improved functional outcome in the experimental animals. The functional improvement is not necessarily related to cell engraftment; rather, immunomodulation by molecular factors secreted by MSCs is responsible for the beneficial effects of this therapy. However, MSC therapy has a few drawbacks including tumor formation, which can be avoided by the use of MSC-derived exosomes. This review has focused on the research works published in the field of regenerative therapy using MSCs after TBI and its future direction.
Topics: Animals; Brain Injuries, Traumatic; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Regenerative Medicine; Translational Research, Biomedical
PubMed: 31203262
DOI: 10.1515/revneuro-2019-0002 -
Journal of Cellular Biochemistry Jan 2019To date, stem cell-based therapies for cardiac diseases have not achieved any significant clinical accomplishment. Globally, numerous patients are currently treated with... (Review)
Review
To date, stem cell-based therapies for cardiac diseases have not achieved any significant clinical accomplishment. Globally, numerous patients are currently treated with autologous stem cells. The safety and practicality of this technique have been well-examined, its disadvantages have been recognized, and many trials have been proposed. Inadequate description of the implemented cell types, a variety of cell-handling proficiencies, and concerning factors related to autologous stem cells have been known as the central elements restricting the approval of cell-based therapies. The idea that bone marrow (BM)-derived cells could be applied to regenerate and cure damage in various organs is the basis for bone marrow mononuclear cell (BMMNC) therapy for heart disease. Mesenchymal stem cells (MSCs) are a part of the BMMNCs; on one hand, they have the capability to differentiate into various tissues, and, on the other, their immunomodulatory effects have been considered and clinically confirmed in different experiments. In this review, we summarize the knowledge obtained by trials in which mesenchymal cell-based therapy has been practiced. Furthermore, we accentuate the developments in the purification and lineage specification of MSCs as well as BMMNCs that have influenced the progress of future stem cell-based therapies with special attention on cardiovascular disease.
Topics: Bone Marrow Cells; Cardiomyopathies; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells
PubMed: 30191597
DOI: 10.1002/jcb.27531