International Journal of Molecular Medical Science, 2024, Vol.14, No.3, 167-176 http://medscipublisher.com/index.php/ijmms 172 determining the optimal cell source, dosage, timing and route of administration. Further mechanism research, especially in-depth exploration of the interaction between MSCs and the host immune system, will provide important information for improving treatment efficacy. Meanwhile, implementing large-scale, multicenter, randomized controlled clinical trials will help validate the efficacy and safety of MSCs in preventing GVHD. Exploring the combined application of MSCs with other prevention or treatment methods for GVHD is also a promising research direction. In addition, finding ways to reduce costs and addressing ethical issues are also key to promoting the widespread application of MSCs in transplant medicine. 4 The Application of Mesenchymal Stem Cells in the Treatment of GVHD 4.1 Clinical trials and efficacy evaluation of mesenchymal stem cells in GVHD treatment In the past few years, mesenchymal stem cells (MSCs) have shown significant therapeutic potential in the treatment of graft-versus-host disease (GVHD), attracting widespread clinical research interest. Multiple clinical trials mainly focus on evaluating the safety and effectiveness of MSCs in treating acute and chronic GVHD, while examining their potential improvements in patient survival and quality of life. The current research results indicate that the application of MSCs in the treatment of GVHD is generally considered safe and has not caused significant adverse events such as allergic reactions, acute toxicity, or increased risk of infection. However, for the potential risks of MSCs promoting tumor growth, long-term safety still needs to be continuously monitored and evaluated. In terms of effectiveness, MSCs have shown varying degrees of effectiveness in alleviating acute and chronic GVHD symptoms. Especially for some patients with refractory acute GVHD, MSCs treatment can significantly reduce symptom severity and improve survival rate. Resnick et al. (2013) reported the results of MSC treatment in 50 patients with acute GVHD. These patients did not show any response after receiving hormone therapy for at least 3 days (≥ 1 mg/kg/day). This study found that among patients receiving MSC treatment, 33% achieved complete remission and 52% achieved partial remission, demonstrating the potential effectiveness of MSC treatment. Although there is relatively limited data on chronic GVHD, preliminary studies have also shown that MSCs have potential therapeutic benefits for some patients. In addition, MSCs treatment has shown positive effects in improving the long-term survival rate and quality of life of GVHD patients. As shown in the study by Wen et al. (2010), infusion of ex vivo expanded MSCs may be a safe and effective rescue therapy for patients with refractory chronic GVHD. 19 stubborn chronic GVHD patients received MSCs treatment from volunteer bone marrow, of which 14 patients (73.7%) had a good response to MSCs treatment, achieving complete remission (CR) or partial remission (PR). After treatment, some surviving patients were able to reduce immunosuppressive agents to below 50% of the initial dose, and 5 patients were able to completely discontinue immunosuppressive agents. However, there are significant individual differences in the effectiveness of MSCs treatment, which may be related to various factors such as the treatment plan (such as the source, dosage, and timing of MSCs) and the patient's own conditions. Therefore, future research will need to focus on optimizing treatment plans, determining the most suitable cell dose, infusion timing, and treatment frequency. Exploring the mechanism of action of MSCs and developing biomarkers for predicting treatment outcomes is of great significance for improving treatment outcomes and developing personalized treatment strategies. 4.2 Mechanism of action of MSCs in the treatment of GVHD The mechanism of action of mesenchymal stem cells (MSCs) in the treatment of graft-versus-host disease (GVHD) involves their strong immune regulatory function and ability to promote tissue repair, which constitutes the multifaceted impact of MSCs in the treatment of GVHD. MSCs reduce attacks on host tissues by inhibiting the activation and proliferation of effector T cells, which is achieved through direct contact and secretion of anti-inflammatory cytokines such as TGF- β Implemented with PGE2. Meanwhile, MSCs also promote the generation and function of regulatory T cells (Tregs), which play a crucial role in maintaining immune tolerance and inhibiting GVHD. In addition, the impact of MSCs on B cell function is achieved by inhibiting B cell proliferation and antibody production, alleviating autoimmune reactions, while also regulating the function of natural killer (NK) cells and dendritic cells (DC), further reducing the intensity of immune responses.
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