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Biological functions of mesenchymal stem cells and clinical implications

Biological functions of mesenchymal stem cells and clinical implications

Biological functions of mesenchymal stem cells and clinical implications

Mesenchymal stem cells (MSCs) are isolated from various biological tissues, including adult bone marrow, adipose tissues, and neonatal tissues like the umbilical cord and placenta. MSCs exhibit biological properties such as extensive proliferation ability and multipotency in vitro. Furthermore, MSCs have been shown to have trophic, homing/migration, and immunosuppressive functions in vitro and in vivo. MSCs are being used in several clinical trials to treat severe degenerative and inflammatory diseases, such as Crohn’s disease and graft-versus-host disease, either alone or in combination with other drugs.

MSCs are promising for therapeutic applications due to their ease of acquisition, genetic stability, low immunogenicity, and curative properties for tissue repair and immunomodulation. The robustness of MSC biological functions, which should be linked to their therapeutic potency, may be critical to the success of MSC therapy in degenerative and inflammatory diseases.

The biological roles of MSCs

MSCs can suppress the immune response in inflammatory cytokine-rich situations such as infections, wounds, or immune-mediated disorders. MSCs suppressed T cell activation and proliferation while suppressing T cell activation and proliferation in preclinical and clinical trials. This special performance of MSCs in the presence of MSC polarization is defined as the absence of inflammatory mediators. MSCs can migrate to damaged areas following systemic infusion and, as a result, exert a beneficial effect via various mechanisms, most notably immunoregulation and angiogenesis. Although the related mechanism of MSC immunosuppression is not entirely clear, cellular interaction, accompanied by multiple factors, plays the most important role in this process. MSCs release several cytokines, including TGF- and hepatocyte growth factor (HGF), and produce soluble factors such as indoleamine 2,3-dioxygenase (IDO), PGE2, and nitric oxide in the presence of high levels of inflammatory cytokines such as TNF- and IFN (NO). To increase immunomodulation effects, these mediators suppress T effector cells while increasing the expression of FOXP3, CTLA4, and GITR in regulatory T cells (Tregs). Furthermore, cell-to-cell communication facilitates Treg stimulation by cytokine-primed MSCs. Overexpression of inducible co-stimulator ligands (ICOSL) stimulates effective Tregs.

Furthermore, MSCs can indirectly stimulate the generation of Treg cells. In an in vitro study, MSCs stimulated M2 macrophages and altered their phenotype through the secretion of extracellular vesicles, according to the literature. M2 cells activated by MSCs also express CCL-18 and induce Treg cells. Furthermore, MSCs increase the expression of COX2 and IDO, resulting in CD206 and CD163 in M2 cells and the expression of IL-6 and IL-10 in the microenvironment. Overexpression of IL-10 by dendritic cells (DCs) and M2 cells in the presence of MSCs leads to further immunomodulation via inhibition of effector T cells. Furthermore, IDO secretion from MSCs can stimulate B cell proliferation, activation, and IgG release, thereby suppressing T effector cells.

One of the typical properties of MSCs is their multipotency capacity, in which these stem cells are able to differentiate into a number of tissues in vitro. Chondrogenic differentiation of MSCs in vitro occurs commonly via culturing them in the presence of TGF-1 or TGF-3, IGF-1, FGF-2, or BMP-2. An increase in the expression of several genes, including collagen types II and IX, aggrecan, and others, characterizes MSC differentiation into chondroblasts. And the proliferation of chondroblast cell morphology. During the process of chondrogenesis, FGF-2 promotes the MSCs induced with TGF-1, TGF-3, and/or IGF-1. Several molecular pathways have been identified in the literature, including a hedgehog, Wnt/-catenin, TGF-s, and others. BMPs and FGFs can regulate chondrogenesis. Furthermore, MSCs can perform osteogenesis by MSC induction with ascorbic acid, glycerophosphate, vitamin D3, and BMP-2, BMP-4, BMP-6, and BMP-7.

Antifibrinolytic activity is one of MSCs’ most essential properties. In vivo and in vitro, these cells can differentiate into various cell lineages, such as hepatocytes. MSCs contain a variety of trophic factors that cause cell and matrix remodeling to stimulate progenitor cells and the recovery of damaged cells. MSCs can reduce myofibroblasts and reverse the fibrotic activity of injured tissues. Furthermore, these cells release pro-angiogenic factors such as VEGF and IGF-1 and anti-inflammatory factors that aid in tissue function recovery. In a mouse model of heart disease, for example, MSCs can increase the neovascularization of ischemic myocardium via VEGF; similarly, IGF-1 promotes cardiomyocyte survival and proliferation.

Clinical implications of Mesenchymal stem cells

Mesenchymal stem cells (MSCs) have several potential clinical applications, including treating various diseases and injuries. MSCs are found in many tissues throughout the body, including bone marrow, adipose tissue, and umbilical cord tissue. They can differentiate into a variety of cell types, including osteoblasts (bone cells), chondrocytes (cartilage cells), and adipocytes (fat cells). MSCs have been used to treat various conditions, including osteoarthritis, cartilage damage, heart disease, and autoimmune disorders. They can also be used to promote tissue repair and regeneration and to reduce inflammation.

MSCs are also being studied for their potential in regenerative medicine, as they can generate new cells and tissue to replace damaged or diseased cells. Also, MSCs have been used in cancer treatment, as they have been shown to suppress the growth and spread of cancer cells.

However, more research is needed to fully understand the mechanisms of action of MSCs fully and determine the most effective ways to use them in clinical practice. Also, the ethical issues related to the collection, culturing, and use of MSCs must be considered.

Read also: Top Tips for Medical Tourism in Thailand

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