不同策略提高间充质干细胞治疗肝纤维化:效果与潜在风险分析

Different strategies to enhance mesenchymal stem cells in treatment of liver fibrosis:analysis of efficacy and potential risks

背景:目前大量研究表明,间充质干细胞联合不同治疗策略能更有效地改善肝纤维化,抑制其向终末期肝病发展。目的:探讨间充质干细胞联合不同策略改善肝纤维化疗效优于单独间充质干细胞治疗的相关机制。方法:由第一作者应用计算机在中国知网、万方、维普、PubMed、Web of Science和Nature数据库中检索涉及间充质干细胞联合不同策略改善肝纤维化的研究,中文检索词为“间充质干细胞,肝纤维化,联合治疗,肝星状细胞”,英文检索词为“mesenchymal stem/stromal cells,liver/hepatic fibrosis/cirrhosis,combination therapy,hepatic stellate cells/HSCs”,通过快速浏览文章题目及摘要进行筛选,排除与主题关系不密切的文章,最终筛选出104篇文献进行综述分析。结果与结论:间充质干细胞通过分化为肝样细胞、抑制肝星状细胞活化、免疫调节等机制来改善肝纤维化,但间充质干细胞移植后肝脏定植率低、存活率低、作用时间短等原因限制了其临床应用。间充质干细胞联合药物、基因修饰、细胞因子等多种治疗策略改善肝纤维化的疗效优于间充质干细胞单独治疗,并且间充质干细胞联合不同策略通过促进间充质干细胞归巢、抑制肝星状细胞活化、调节微环境、调控信号通路等机制更有效地改善肝纤维化。间充质干细胞还可以通过预处理、miRNA调控及与其他细胞联合,使间充质干细胞在减轻肝纤维化方面表现出更好的肝源性分化、归巢和存活功能。间充质干细胞联合不同策略并不能规避间充质干细胞单独治疗肝纤维化的潜在风险,而且这些策略(药物、基因修饰和细胞因子等)自身安全性也值得考虑。此外,间充质干细胞移植数量和途径等有待进一步研究。

BACKGROUND:At present,a large number of studies have shown that mesenchymal stem cells can be combined with different strategies to more effectively improve liver fibrosis and inhibit its progression to end-stage liver disease.OBJECTIVE:To explore the mechanism of mesenchymal stem cells combined with different strategies to improve liver fibrosis compared with mesenchymal stem cells alone.METHODS:The first author used computers to search CNKI,WanFang,VIP,PubMed,Web of Science,and Nature databases involving mesenchymal stem cells combined with different strategies to improve liver fibrosis.The search terms were“mesenchymal stem cells,liver fibrosis,combination therapy,liver stellate cells”in Chinese,and“mesenchymal stem/stromal cells,liver/hepatic fibrosis/cirrhosis,combination therapy,hepatic stellate cells/HSCs”in English.By quickly browsing the title and abstract of the article,excluding the articles that are not closely related to the topic,104 articles were finally selected for review analysis.RESULTS AND CONCLUSION:Mesenchymal stem cells improve liver fibrosis by differentiating into hepato-like cells,inhibiting hepatic stellate cell activation,immune regulation,and other mechanisms.However,the low rate of liver colonization,low survival rate,and short action time of mesenchymal stem cells after transplantation limit their clinical application.Mesenchymal stem cells can improve liver fibrosis through a combination of drugs,gene modification,cytokines and other strategies,and the efficacy is better than that of mesenchymal stem cells alone.Moreover,the combination of mesenchymal stem cells and different strategies can effectively improve liver fibrosis by promoting mesenchymal stem cell homing,inhibiting hepatic stellate cell activation,regulating the microenvironment,and regulating signaling pathways.Mesenchymal stem cells can also show better liver-derived differentiation,homing and survival functions in reducing liver fibrosis through pretreatment,miRNA regulation and combination with other cells.The combination of mesenchymal stem cells and different strategies cannot avoid the potential risks of mesenchymal stem cells alone in the treatment of liver fibrosis,and the safety of these strategies(drugs,gene modifications,cytokines,etc.)is also worth considering.In addition,the number and route of mesenchymal stem cell transplantation need to be further studied.