A revealing review of mesenchymal stem cells therapy, clinical perspectives, and Modification strategies
Mesenchymal stem cells (MSCs) are hierarchical postnatal stem cells capable of self-renewal and maintaining a diverse power of differentiation across multiple lineages. MSCs are emerging as a prominent topic in recent research due to their biological and clinical importance. Applications. MSCs possess distinctive features such as; ease of isolation and cultivation, plasticity, and intrinsic tropism toward the injured area (homing). They also have anti-inflammatory and antiapoptotic activity in tissues at risk and an immunomodulatory effect due to paracrine function, antimicrobial activity, and bacterial elimination action. They can activate other resident stem cells and stimulate neoangiogenesis. These exceptional properties make MSCs a viable resource for the clinical treatment of some human diseases.
What are MSCs and their potentials?
Mammalian bone marrow is responsible for hematopoiesis and bone homeostasis. It includes a heterogeneous population of hematopoietic and non-hematopoietic stem cells, such as B., the precursors of fibroblasts, known as MSCs. The International Society for Cell Therapy (ISCT) has defined criteria for MSCs. MSCs must adhere to plastic and differentiate into osteoblast, adipocyte, and chondroblast lineages.
MSCs mechanisms of therapy
Migration
“Migration” is the process of the selective ability of MSCs to migrate to the site of injury and the sustained delivery of trophic signals. Expressing specific ligands or receptors by damaged tissue facilitates transport, adhesion, and infiltration of MSCs into the injured site.
Tissue repair and regeneration
Several functional properties make MSCs suitable for tissue regeneration and repair. These properties include the ability of MSCs to differentiate into different cell lineages, their ability to migrate to injured tissues, angiogenesis, antiapoptotic activity, and finally, their ability to secrete soluble bioactive factors.
Immunomodulation
Several cytokines and regulatory factors are likely to be attributed to the immunomodulatory properties of MSCs. These factors, including IL10, TGFβ, PGE2, IDO, NO, and FAS/FASL, likely affect the proliferation and function of some immune cells such as B and T lymphocytes, dendritic cells, natural killer cells, monocytes, neutrophils, and macrophages. MSCs can arrest B cell proliferation and maturation, alter isotype switching, inhibit chemotaxis, upregulate antibody (IgG) secretion, decrease pro-inflammatory cytokine secretion by Th1 cells, decrease IL-4 secretion by Th2, Increase cells inhibiting T cell proliferation, regulatory molecule formation, increases T cells and reduces the cytotoxic effects of CTL.
Anti-inflammatory effects
The anti-inflammatory effects of MSCs protect the host by dampening the severity of the immune response to inflammation. An overall reduction in local and systemic inflammation is achieved through a proportional decrease in pro-inflammatory cytokines and an increase in anti-inflammatory cytokines.
Antiapoptotic activity
MSCs can protect injured cells and preserve organ function by inhibiting programmed cell death through paracrine signaling. The antiapoptotic mechanisms of MSCs include up-regulation of DNA repair, down-regulation of mitochondrial death pathways, increased antioxidant activity, and alteration of anti- and pro-apoptotic protein expression mechanisms. Mediators secreted by MSCs include SDF-1, IGF-1, Nrf2, HIF, HO-1, and VEGF, which downregulate pro-apoptotic proteins.
Neoangiogenesis
MSCs can promote neovascularization in injured tissues by expressing angiogenic cytokines such as VEGF, FGF1,2 (fibroblast growth factor), HGF (hepatocyte growth factor), Ang-1,2 (angiopoietin), and SDF-1. The soluble factors of MSCs make them capable of enhancing tissue vascularization by stimulating endothelial cell regrowth and neoangiogenesis.
Antimicrobial Effects
MSCs are endowed with an intrinsic bactericidal mechanism by secreting antimicrobial peptides such as LL-37 and lipocalin-2 in response to stimulation by pathogens. MSC-derived antimicrobial factors will most likely disrupt bacterial membranes and contribute to bacterial clearance.
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