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Transfusion and Apheresis Science :... Feb 2021Mesenchymal stromal cells (MSC) are multipotent precursor cells that can be derived from a variety of tissue sources, with a working definition based on... (Review)
Review
Mesenchymal stromal cells (MSC) are multipotent precursor cells that can be derived from a variety of tissue sources, with a working definition based on immunophenotyping and cell differentiation capacity. Despite historical roots in the field of tissue engineering, they have generated great interest as cell therapies for their immune regulatory function, which has led to numerous clinical trials for a range of inflammatory and autoimmune conditions. Importantly, due to the lack of traditional MHC expression and their expression of other immune regulatory proteins, they can be used from third party donors without generating a dangerous alloreactivity. After 20 years of clinical trials, they have earned themselves an excellent safety record but are currently only approved for use in Canada, New Zealand, Japan, South Korea and Europe due to a lack of consistent efficacy data. In the United States, the indication that has seen the most progress is steroid refractory acute graft-versus-host disease (SR-aGVHD). Issues with early clinical trials can be attributed to both challenges with defining optimal patient populations and trial design as well as limitations related to commercial manufacturing. Earlier this year, the encouraging data for a repeat Phase III trial in pediatric patients with SR-aGVHD was published. This review provides information on the proposed mechanism of action of MSCs, clinical utilization of MSCs with focus on SR-aGVHD and potential modalities that can improve the efficacy of MSCs.
Topics: Female; Humans; Male; Mesenchymal Stem Cells
PubMed: 33495081
DOI: 10.1016/j.transci.2021.103058 -
Stem Cell Research & Therapy Jun 2016Mesenchymal stem cells have been used for cardiovascular regenerative therapy for decades. These cells have been established as one of the potential therapeutic agents,... (Review)
Review
Mesenchymal stem cells have been used for cardiovascular regenerative therapy for decades. These cells have been established as one of the potential therapeutic agents, following several tests in animal models and clinical trials. In the process, various sources of mesenchymal stem cells have been identified which help in cardiac regeneration by either revitalizing the cardiac stem cells or revascularizing the arteries and veins of the heart. Although mesenchymal cell therapy has achieved considerable admiration, some challenges still remain that need to be overcome in order to establish it as a successful technique. This in-depth review is an attempt to summarize the major sources of mesenchymal stem cells involved in myocardial regeneration, the significant mechanisms involved in the process with a focus on studies (human and animal) conducted in the last 6 years and the challenges that remain to be addressed.
Topics: Animals; Biomarkers; Cell- and Tissue-Based Therapy; Clinical Trials as Topic; Gene Expression; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Myocardial Infarction; Myocardium; Neovascularization, Physiologic; Regeneration; Regenerative Medicine; Research Report; Stem Cell Niche
PubMed: 27259550
DOI: 10.1186/s13287-016-0341-0 -
Zhongguo Xiu Fu Chong Jian Wai Ke Za... Feb 2015To comprehensively analyze the recent advancements in the field of mesenchymal stem cells (MSCs) derived exosomes (MSCs-exosomes) in tissue repair. (Review)
Review
OBJECTIVE
To comprehensively analyze the recent advancements in the field of mesenchymal stem cells (MSCs) derived exosomes (MSCs-exosomes) in tissue repair.
METHODS
The literature about MSCs-exosomes in tissue repair was reviewed and analyzed.
RESULTS
Exosomes are biologically active microvesicles released from MSCs which are loaded with functional proteins, RNA, and microRNA. Exosomes can inhibit apoptosis, stimulate proliferation, alter cell phenotype in tissue repair of several diseases through cell-to-cell communication.
CONCLUSION
MSCs-exosomes is a novel source for the treatment of tissue repair. Further research of MSCs-exosomes biofunction, paracellular transport, and treatment mechanism will help the transform to clinical application.
Topics: Apoptosis; Cell Communication; Exosomes; Humans; Mesenchymal Stem Cells; MicroRNAs; Regeneration; Wound Healing
PubMed: 26455156
DOI: No ID Found -
Cytotherapy 2005The plastic-adherent cells isolated from BM and other sources have come to be widely known as mesenchymal stem cells (MSC). However, the recognized biologic properties...
The plastic-adherent cells isolated from BM and other sources have come to be widely known as mesenchymal stem cells (MSC). However, the recognized biologic properties of the unfractionated population of cells do not seem to meet generally accepted criteria for stem cell activity, rendering the name scientifically inaccurate and potentially misleading to the lay public. Nonetheless, a bona fide MSC most certainly exists. To address this inconsistency between nomenclature and biologic properties, and to clarify the terminology, we suggest that the fibroblast-like plastic-adherent cells, regardless of the tissue from which they are isolated, be termed multipotent mesenchymal stromal cells, while the term mesenchymal stem cells is used only for cells that meet specified stem cell criteria. The widely recognized acronym, MSC, may be used for both cell populations, as is the current practice; thus, investigators must clearly define the more scientifically correct designation in their reports. The International Society for Cellular Therapy (ISCT) encourages the scientific community to adopt this uniform nomenclature in all written and oral communications.
Topics: Mesenchymal Stem Cells; Multipotent Stem Cells; Stromal Cells; Terminology as Topic
PubMed: 16236628
DOI: 10.1080/14653240500319234 -
Handbook of Experimental Pharmacology 2006Mesenchymal stem cells (MSC), one type of adult stem cell, are easy to isolate, culture, and manipulate in ex vivo culture. These cells have great plasticity and the... (Review)
Review
Mesenchymal stem cells (MSC), one type of adult stem cell, are easy to isolate, culture, and manipulate in ex vivo culture. These cells have great plasticity and the potential for therapeutic applications, but their properties are poorly understood. MSCs can be found in bone marrow and in many other tissues, and these cells are generally identified through a combination of poorly defined physical, phenotypic, and functional properties; consequently, multiple names have been given to these cell populations. Murine MSCs have been directly applied to a wide range of murine models of diseases, where they can act as therapeutic agents per se, or as vehicles for the delivery of therapeutic genes. In addition to their systemic engraftment capabilities, MSCs show great potential for the replacement of damaged tissues such as bone, cartilage, tendon, and ligament. Their pharmacological importance is related to four points: MSCs secrete biologically important molecules, express specific receptors, can be genetically manipulated, and are susceptible to molecules that modify their natural behavior. Due to their low frequency and the lack of knowledge on cell surface markers and their location of origin, most information concerning MSCs is derived from in vitro studies. The search for the identity of the mesenchymal stem cell has depended mainly on three culture systems: the CFU-F assay, the analysis of bone marrow stroma, and the cultivation of mesenchymal stem cell lines. Other cell populations, more or less related to the MSC, have also been described. Isolation and culture conditions used to expand these cells rely on the ability of MSCs, although variable, to adhere to plastic surfaces. Whether these conditions selectively favor the expansion of different bone marrow precursors or cause similar cell populations to acquire different phenotypes is not clear. The cell populations could also represent different points of a hierarchy or a continuum of differentiation. These issues reinforce the urgent need for a more comprehensive view of the mesenchymal stem cell identity and characteristics.
Topics: Animals; Cell Culture Techniques; Cell Differentiation; Cell Separation; Genetic Therapy; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells
PubMed: 16370331
DOI: No ID Found -
Haematologica Feb 2009Mesenchymal stem cells are adherent stromal cells, initially isolated from the bone marrow, characterized by their ability to differentiate into mesenchymal tissues such... (Review)
Review
Mesenchymal stem cells are adherent stromal cells, initially isolated from the bone marrow, characterized by their ability to differentiate into mesenchymal tissues such as bone, cartilage and fat. They have also been shown to suppress immune responses in vitro. Because of these properties, mesenchymal stem cells have recently received a very high profile. Despite the dramatic benefits reported in early phase clinical trials, their functions remain poorly understood. Particularly, several questions remain concerning the origin of mesenchymal stem cells and their relationship to other stromal cells such as fibroblasts. Whereas clear gene expression signatures are imprinted in stromal cells of different anatomical origins, the anti-proliferative effects of mesenchymal stem cells and fibroblasts and their potential to differentiate appear to be common features between these two cell types. In this review, we summarize recent studies in the context of historical and often neglected stromal cell literature, and present the evidence that mesenchymal stem cells and fibroblasts share much more in common than previously recognized.
Topics: Fibroblasts; Humans; Immune Tolerance; Mesenchymal Stem Cells; Stromal Cells
PubMed: 19109217
DOI: 10.3324/haematol.13699 -
Acta Biomaterialia Sep 2017In vitro maturation of engineered vascular tissues (EVT) requires the appropriate incorporation of smooth muscle cells (SMC) and extracellular matrix (ECM) components...
UNLABELLED
In vitro maturation of engineered vascular tissues (EVT) requires the appropriate incorporation of smooth muscle cells (SMC) and extracellular matrix (ECM) components similar to native arteries. To this end, the aim of the current study was to fabricate 4mm inner diameter vascular tissues using mesenchymal progenitor cells seeded into tubular scaffolds. A dual-pump bioreactor operating either in perfusion or pulsatile perfusion mode was used to generate physiological-like stimuli to promote progenitor cell differentiation, extracellular elastin production, and tissue maturation. Our data demonstrated that pulsatile forces and perfusion of 3D tubular constructs from both the lumenal and ablumenal sides with culture media significantly improved tissue assembly, effectively inducing mesenchymal progenitor cell differentiation to SMCs with contemporaneous elastin production. With bioreactor cultivation, progenitor cells differentiated toward smooth muscle lineage characterized by the expression of smooth muscle (SM)-specific markers smooth muscle alpha actin (SM-α-actin) and smooth muscle myosin heavy chain (SM-MHC). More importantly, pulsatile perfusion bioreactor cultivation enhanced the synthesis of tropoelastin and its extracellular cross-linking into elastic fiber compared with static culture controls. Taken together, the current study demonstrated progenitor cell differentiation and vascular tissue assembly, and provides insights into elastin synthesis and assembly to fibers.
STATEMENT OF SIGNIFICANCE
Incorporation of elastin into engineered vascular tissues represents a critical design goal for both mechanical and biological functions. In the present study, we seeded porous tubular scaffolds with multipotent mesenchymal progenitor cells and cultured in dual-pump pulsatile perfusion bioreactor. Physiological-like stimuli generated by bioreactor not only induced mesenchymal progenitor cell differentiation to vascular smooth muscle lineage but also actively promoted elastin synthesis and fiber assembly. Gene expression and protein synthesis analyses coupled with histological and immunofluorescence staining revealed that elastin-containing vascular tissues were fabricated. More importantly, co-localization and co-immunoprecipitation experiments demonstrated that elastin and fibrillin-1 were abundant throughout the cross-section of the tissue constructs suggesting a process of elastin protein crosslinking. This study paves a way forward to engineer elastin-containing functional vascular substitutes from multipotent progenitor cells in a bioreactor.
Topics: Bioreactors; Cell Differentiation; Cell Line; Elasticity; Elastin; Humans; Induced Pluripotent Stem Cells; Mesenchymal Stem Cells; Myocytes, Smooth Muscle; Tissue Scaffolds
PubMed: 28690007
DOI: 10.1016/j.actbio.2017.07.012 -
Bioscience Reports May 2019The present study was carried out to investigate and compare the differentiation potential of mesenchymal stem cells (MSCs) isolated from human dental tissues (pulp,...
The present study was carried out to investigate and compare the differentiation potential of mesenchymal stem cells (MSCs) isolated from human dental tissues (pulp, papilla, and follicle) of the same donor. MSCs were isolated from dental tissues (pulp, papilla, and follicle) following digestion method and were analyzed for the expression of pluripotent markers and cell surface markers. All three types of MSCs were evaluated for their potential to differentiate into mesenchymal lineages. Further, the MSCs were differentiated into pancreatic β cell-like cells using multistep protocol and characterized for the expression of pancreatic lineage specific markers. Functional properties of differentiated pancreatic β cell-like cells were assessed by dithizone staining and glucose challenge test. All three types of MSCs showed fibroblast-like morphology upon culture and expressed pluripotent, and mesenchymal cell surface markers. These MSCs were successfully differentiated into mesenchymal lineages and transdifferentiated into pancreatic β cell-like cells. Among them, dental follicle derived MSCs exhibits higher transdifferentiation potency toward pancreatic lineage as evaluated by the expression of pancreatic lineage specific markers both at mRNA and protein level, and secreted higher insulin upon glucose challenge. Additionally, follicle-derived MSCs showed higher dithizone staining upon differentiation. All three types of MSCs from a single donor possess similar cellular properties and can differentiate into pancreatic lineage. However, dental follicle derived MSCs showed higher potency toward pancreatic lineage than pulp and papilla derived MSCs, suggesting their potential application in future stem cell based therapy for the treatment of diabetes.
Topics: Adolescent; Antigens, Differentiation; Cell Differentiation; Cells, Cultured; Dental Pulp; Gene Expression Regulation; Humans; Insulin-Secreting Cells; Male; Mesenchymal Stem Cells
PubMed: 31015367
DOI: 10.1042/BSR20182051 -
Developmental Biology May 2018Mesenchymal stem cells (MSCs) are stromal cells that display self-renewal and multipotent differentiation capacity. The repertoire of mature cells generated ranges but... (Review)
Review
Mesenchymal stem cells (MSCs) are stromal cells that display self-renewal and multipotent differentiation capacity. The repertoire of mature cells generated ranges but is not restricted to: fat, bone and cartilage. Their potential importance for both cell therapy and maintenance of in vivo homeostasis is indisputable. Nonetheless, both their in vivo identity and use in cell therapy remain elusive. A drawback generated by this fact is that little is known about the MSC niche and how it impacts differentiation and homeostasis maintenance. Hence, the roles played by the extracellular matrix (ECM) and its main regulators namely: the Matrix Metalloproteinases (MMPs) and their counteracting inhibitors (TIMPs and RECK) upon stem cells differentiation are only now beginning to be unveiled. Here, we will focus on mesenchymal stem cells and review the main mechanisms involved in adipo, chondro and osteogenesis, discussing how the extracellular matrix can impact not only lineage commitment, but, also, their survival and potentiality. This review critically analyzes recent work in the field in an effort towards a better understanding of the roles of Matrix Metalloproteinases and their inhibitors in the above-cited events.
Topics: Animals; Cell Differentiation; Extracellular Matrix; Humans; Mesenchymal Stem Cells; Signal Transduction
PubMed: 29544769
DOI: 10.1016/j.ydbio.2018.03.002 -
The International Journal of... 2008Mesenchymal stem cells were initially characterized as plastic adherent, fibroblastoid cells. In recent years, there has been an increasing focus on mesenchymal stem... (Review)
Review
Mesenchymal stem cells were initially characterized as plastic adherent, fibroblastoid cells. In recent years, there has been an increasing focus on mesenchymal stem cells since they have great plasticity and are potential for therapeutic applications. Mesenchymal stem cells or mesenchymal stem cell-like cells have been shown to reside within the connective tissues of most organs. These cells can differentiate into osteogenic, adipogenic and chondrogenic lineages under appropriate conditions. A number of reports have also indicated that these cells possess the capacity to trans-differentiate into epithelial cells and lineages derived from the neuro-ectoderm, and in addition, mesenchymal stem cells can migrate to the sites of injury, inflammation, and to tumors. These properties of mesenchymal stem cells make them promising candidates for use in regenerative medicine and may also serve as efficient delivery vehicles in site-specific therapy.
Topics: Cell Differentiation; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Regenerative Medicine
PubMed: 18295530
DOI: 10.1016/j.biocel.2008.01.007