International Journal of Molecular Medical Science, 2024, Vol.14, No.3, 167-176 http://medscipublisher.com/index.php/ijmms 170 2.2 The mechanism of action of MSCs in the immune system Mesenchymal stem cells (MSCs) play a crucial immune regulatory role in the immune system, achieving their functions through a series of complex mechanisms. These mechanisms include direct and indirect regulation of various immune cells, thereby having a profound impact on immune responses. Firstly, MSCs are able to directly contact or secrete specific inhibitory factors, such as transforming growth factors β (TGF-β) and prostaglandin E2 (PGE2) is used to inhibit the proliferation and activation of T cells. This effect not only limits the spread of inflammatory reactions, but also promotes the generation of regulatory T cells (Tregs), thereby enhancing the immunosuppressive environment in the body. In addition to regulating T cells, MSCs also affect B cell function by inhibiting B cell proliferation, maturation, and antibody secretion, thereby regulating humoral immune responses and reducing the production of autoantibodies. In addition, MSCs can also reduce the cytotoxic effects of natural killer cells (NK) and interferon γ (IFN-γ) by inhibiting the maturation and antigen-presenting ability of dendritic cells (DCs) and reducing T cell activation, the immune response can be regulated at both natural and adaptive immune levels. Xiang et al. (2017) explored the application of MSCs in the treatment of glioma, emphasizing the potential of MSCs as cell therapeutic agents. The anti proliferative, anti-inflammatory, and anti apoptotic effects of MSCs have a protective effect on nerve cells, indicating their dual functions in regulating immune responses and supporting tissue regeneration. Caplan and Correa (2011) proposed that MSCs can be released from their perivascular positions during injury, activated, and establish a regenerative microenvironment by secreting bioactive molecules and regulating local immune responses. These nutritional and immune regulatory activities indicate that MSCs can act as pharmacies for site regulation in the body. The immune regulatory function of MSCs is not limited to inhibiting immune responses, but they can also promote tissue repair and regeneration by secreting various growth factors, such as vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), thus playing a dual role in immune-mediated diseases and tissue damage. By creating an immune tolerant microenvironment, MSCs have shown great potential in the treatment of autoimmune diseases, inflammatory diseases, and the prevention and treatment of graft-versus-host disease (GVHD) in transplant medicine. 3 The Application of 3 MSCs in Preventing GVHD 3.1 Research on MSCs for preventing GVHD in preclinical and clinical studies In preclinical and clinical studies, mesenchymal stem cells (MSCs) have been widely studied as a potential strategy for preventing graft-versus-host disease (GVHD). These studies focus on evaluating the safety, efficacy, and how MSCs can prevent or reduce the severity of GVHD through immune regulatory mechanisms. Preclinical studies, mainly conducted through animal models, have shown the positive effects of MSCs in preventing GVHD. In these studies, MSCs have been shown to reduce the release of inflammatory cytokines, inhibit the activation and proliferation of effector T cells, promote the formation of regulatory T cells, and thus alleviate the symptoms of GVHD. For example, studies in mouse models have shown that untreated mice exhibit more severe GVHD symptoms, including skin and liver damage, compared to mice treated with MSCs before and after transplantation. Lim et al. (2017) found that MSCs significantly alleviate the clinical and pathological severity of acute skin sclerosing GVHD in a mouse model by inhibiting skin infiltration of immune effector cells. Research has found that MSCs can significantly reduce collagen production in the skin and consistently decrease Tgfb expression. In addition, MSCs inhibit the infiltration of immune effector cells by downregulating the expression of CCR4 and CCR8 on CD4+T cells and CCR1 expression on CD11b+monocytes/macrophages. These preclinical studies provide a foundation for the application of MSCs in human GVHD prevention strategies.
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