Objective To systematically review recent research advances in mesenchymal stem cells (MSCs) for preventing the progression of end-stage liver disease to hepatocellular carcinoma (HCC), with a focus on their mechanisms of action, clinical application prospects, and major challenges. Method A systematic search of recent domestic and international literature was conducted, and the findings were summarized and reviewed. Results MSCs exert anti-hepatofibrotic effects through multiple pathways. First, via direct contact or paracrine signaling, MSCs inhibit the activation and proliferation of hepatic stellate cells (HSCs) and promote their apoptosis. Second, by releasing exosomes, MSCs deliver functional microRNA such as miR-455-3p, miR-4465, which target key signaling pathways including phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) and Wnt/β-catenin, thereby suppressing the fibrogenic activity of HSCs. Concurrently, MSCs restore the balance between matrix metalloproteinases and their tissue inhibitors, promoting the degradation of excessively deposited extracellular matrix. Additionally, through the secretion of factors like vascular endothelial growth factor, MSCs improve hepatic microcirculation and oxygen supply, creating a favorable microenvironment for liver tissue repair. MSCs reshape the hepatic immune microenvironment to delay disease progression. By paracrine release of immunomodulatory factors such as prostaglandin E2 and indoleamine 2,3-dioxygenase, MSCs suppress the release of pro-inflammatory cytokines (such as tumor necrosis facto-α, interleukin-17) and promote the production of anti-inflammatory cytokines (such as interleukin-10). This modulates the functions of immune cells including T cells and macrophages, thereby alleviating hepatic inflammation. Notably, the immunomodulatory function of MSCs is highly plastic and heavily dependent on the status of the inflammatory microenvironment; under specific conditions, MSCs may also exert immune-promoting effects, highlighting the complexity of their functionality. Furthermore, MSCs and their exosomes demonstrate direct potential against HCC. MSCs can home to tumor sites and, by delivering anti-tumor molecules such as miR-17-5p or synergizing with drugs like sorafenib, inhibit HCC cell proliferation, induce apoptosis, and reverse drug resistance. Their mechanisms involve the regulation of key oncogenic signaling pathways, such as insulin like growth factor 1 receptor/PI3K/Akt and nuclear factor-κB. Meanwhile, MSCs may influence anti-tumor immune responses by modifying the tumor microenvironment. Conclusions MSCs demonstrate significant potential in preventing the progression of end-stage liver disease to HCC primarily through multi-target and multi-mechanism synergistic actions, including anti-fibrotic, immunomodulatory, and direct anti-tumor effects. However, further standardization of their preparation and application protocols, optimization of clinical translation strategies, and validation of long-term safety and efficacy through high-quality clinical studies are still required.

Citation： YANG Xiting, LUO Le. Mesenchymal stem cells in preventing progression of end-stage liver disease to hepatocellular carcinoma: advances in mechanism research. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2026, 33(2): 263-270. doi: 10.7507/1007-9424.202511037 Copy

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