International Journal of Molecular Medical Science, 2024, Vol.14, No.3, 167-176 http://medscipublisher.com/index.php/ijmms 171 Based on the success of preclinical studies, clinical studies have begun to explore the application of MSCs in preventing human GVHD. These studies include small-scale early-stage trials and some larger randomized controlled trials. Clinical research results indicate that the infusion of MSCs is usually well tolerated by patients and can reduce the incidence and severity of GVHD. For example, Yao et al. (2023) explored the role of mesenchymal stem cells in preventing graft-versus-host disease and found that patients who used MSCs to prevent GVHD had fewer severe forms of acute GVHD. In addition, among patients in the MSCs treatment group, some long-term follow-up showed improved survival rates and quality of life. However, despite many positive results, there is also some variability in clinical studies, partly influenced by factors such as different study designs, sources of MSCs, timing and dosage of administration. In addition, some studies have pointed out that although MSCs can alleviate GVHD symptoms in the short term, their long-term effects and potential side effects still need further research and monitoring. Pallua et al. (2010) found that GvHD significantly affects the role function, overall quality of life, fatigue, breathing difficulties, gastrointestinal side effects, concerns/anxiety, and skin problems of hematopoietic stem cell transplant survivors. 3.2 Mechanisms of MSCs in preventing GVHD Mesenchymal stem cells (MSCs) play a crucial role in preventing graft-versus-host disease (GVHD), and their mechanism mainly depends on their immune regulatory ability. MSCs intervene in immune responses through multiple pathways, significantly reducing the occurrence and severity of GVHD. Fiori et al. (2021) believe that they can inhibit the activation and proliferation of immune cells, especially T and B cells, mainly by secreting a series of anti-inflammatory and immune regulatory factors, such as transforming growth factor β (TGF)- β), Prostaglandin E2 (PGE2), hepatocyte growth factor (HGF), and indoleamine 2,3-dioxygenase (IDO). These factors directly act on immune cells, inhibiting their attack on host tissues. In addition, MSCs also play a role by promoting the formation and function of regulatory T cells (Tregs), which are naturally occurring immunosuppressive cells that can effectively inhibit the development of GVHD. By enhancing the activity of Tregs, MSCs help establish immune tolerance and prevent excessive immune responses. Cuerquis et al. (2014) found that in terms of the balance of inflammatory factors, MSCs reduced pro-inflammatory factors such as tumor necrosis factor α (TNF)- α) And interferon γ (IFN-γ) At the same time, it increases the secretion of anti-inflammatory cytokines such as interleukin-10 (IL-10), which reduces the inflammatory response. Hemeda et al. (2010) found that MSCs also affect the migration of immune cells by regulating the expression of chemical factors and their receptors, reducing their accumulation in common target organs of GVHD such as the liver, intestines, and skin. In addition to immune regulatory effects, MSCs can also secrete growth factors to promote the repair and regeneration of damaged tissues, which is particularly important for reducing tissue damage caused by GVHD. 3.3 Current challenges and future research directions Mesenchymal stem cells (MSCs) have shown enormous therapeutic potential in preventing graft-versus-host disease (GVHD), but their clinical application still faces multiple challenges. Firstly, there are prominent issues with the consistency and reproducibility of research results, which are mainly attributed to differences in the sources, preparation methods, timing of administration, and dosage of MSCs. In addition, although MSCs are generally considered safe, further research is needed on their long-term safety and potential side effects, such as potential tumor promoting effects or impact on host immune surveillance. Meanwhile, the specific mechanism of MSCs in immune regulation is not yet fully understood, and a deeper understanding of the mechanism is crucial for optimizing treatment strategies. Economic costs and ethical issues are also important factors that must be considered when implementing the clinical application of MSCs, especially when dealing with and using MSCs derived from embryos. The future research direction should focus on optimizing the preparation and application procedures of MSCs, including ensuring the safety, efficacy, and consistency of treatment through standardized processes. This involves
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