International Journal of Molecular Medical Science, 2024, Vol.14, No.3, 167-176 http://medscipublisher.com/index.php/ijmms 173 In addition to its immunomodulatory effects, MSCs also promote the repair and regeneration of damaged tissues by secreting various growth factors, particularly in alleviating long-term tissue damage caused by GVHD. Qi et al. (2017) discussed how MSCs interact with the immune system to promote tissue repair, emphasizing the bidirectional regulation between MSCs and immune responses in stem cell-based tissue repair processes. MSCs can also regulate inflammatory responses by secreting anti-inflammatory cytokines and inhibiting pro-inflammatory cytokines such as IL-10 and TNF- α Inhibitors are used to alleviate the inflammatory damage caused by GVHD. Jiang and Xu (2019) discussed that MSCs promote inflammation when the immune system is inactive, and suppress inflammation when the immune system is overactive to avoid self injury. They explored the transition of MSCs from pro-inflammatory to anti-inflammatory phenotypes, effectively regulating their ability to regulate immune responses. Le and Ringdén (2005) reviewed the immunobiology of MSCs, their role in enhancing hematopoietic transplantation implantation, and their use as a preventive and therapeutic approach for acute and chronic GVHD. In the treatment of chronic GVHD, MSCs demonstrate their unique potential in combating chronic GVHD by reducing fibroblast activation and inhibiting collagen deposition, thereby alleviating the fibrosis process. 4.3 Advantages and limitations of mesenchymal stem cell therapy for GVHD The application of mesenchymal stem cells (MSCs) in the treatment of graft-versus-host disease (GVHD) has demonstrated significant advantages, but also faces a series of limitations. MSCs, through their excellent immune regulatory ability, can effectively suppress excessive immune responses and promote immune tolerance, which is particularly important in the treatment of immune mediated diseases such as GVHD. In addition, MSCs can promote the repair and regeneration of damaged tissues, which is crucial for the recovery of GVHD patients. The wide range of sources from various tissues such as bone marrow, fat, umbilical cord blood, and placenta, as well as their low immunogenicity, reduces the risk of immune rejection, making MSCs suitable for allogeneic transplantation. In addition, a large number of clinical trials have proven the relative safety of MSCs application, and no serious adverse events have been observed. Blanc et al. (2008) found that mesenchymal stem cell therapy is effective in severe cases, and MSCs have been successful in treating severe acute GVHD resistant to steroids, with a considerable number of patients achieving complete or partial remission. Kebriaei et al. (2009) found that MSCs are safe and well tolerated in treatment, with few side effects occurring during and immediately after infusion. However, the application of MSCs in the treatment of GVHD also has limitations. The individual differences in treatment effectiveness are significant and are influenced by factors such as the patient's specific situation, the source and quality of MSCs, and the treatment plan. Although MSCs treatment is relatively safe in the short term, its long-term safety, especially regarding the potential risks of promoting tumor growth (Figure 2), still requires more research and long-term monitoring. In addition, the immune regulatory mechanisms of MSCs are complex and not fully understood, which limits the optimization of treatment strategies. The cost issue is also a challenge that cannot be ignored, as high acquisition, cultivation, and application costs may limit its application in resource limited areas. Finally, the use of embryonic derived MSCs may raise ethical and legal issues. Lukomska et al. (2019) believe that the efficacy of MSCs varies greatly among patients, with some patients having no response and long-term benefits not yet fully determined. Kim et al. (2013) argue that the management of MSCs is complex, and the timing and conditions of MSCs management are crucial, especially in the typical pro-inflammatory environment of acute GVHD. This makes the timing of administration crucial for the therapeutic effect. In summary, although MSCs provide a powerful and promising approach for the treatment of severe GVHD, broader clinical trials and long-term follow-up studies are needed to fully understand their efficacy and safety profile. 5 Future Research Directions and Prospects With a deeper understanding of the mechanism of action of mesenchymal stem cells (MSCs) in the treatment of graft-versus-host disease (GVHD), optimizing treatment strategies has become a focus of future research. On the
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