三维培养间充质干细胞成肝分化的表观遗传学特征  

Epigenetic characteristics of hepatogenic differentiation of mesenchymal stem cells in three-dimensional culture

作　　者：黄海纳 余艳荣 毕戬 黄淼 彭维杰 Huang Haina;Yu Yanrong;Bi Jian;Huang Miao;Peng Weijie(Gannan Medical University,Ganzhou 341000,Jiangxi Province,China)

机构地区：[1]赣南医科大学,江西省赣州市341000

出　　处：《中国组织工程研究》2025年第36期7848-7855,共8页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金项目(32460236),项目负责人:彭维杰;江西省研究生创新专项课题(YC2023-S935),项目负责人:黄海纳。

摘　　要：背景:间充质干细胞诱导的成肝细胞样细胞是很有前途的肝再生或肝脏组织工程的种子细胞,传统的二维培养成肝诱导效率低下,越来越多的研究集中在三维培养诱导成肝分化上。目的:总结间充质干细胞成肝诱导的三维培养模型,重点讨论间充质干细胞成肝分化的表观遗传学调控机制研究进展,为提高间充质干细胞成肝分化的效率提供理论依据。方法:检索PubMed数据库及中国知网等数据库收录的相关文献,英文检索词为“mesenchymal stem cells,3D culture,hepatogenic differentiation,hepatocyte-like cells,epigenetics”,中文检索词为“间充质干细胞,三维培养,成肝分化,肝细胞样细胞,表观遗传学”,并结合文献溯源法查找部分文献进行综述分析。结果与结论:(1)目前常见的间充质干细胞成肝分化的三维培养模型包括细胞球、生物支架、生物打印、微流控芯片等,它们在诱导成肝分化过程中各有优势和不足;(2)间充质干细胞成肝分化过程中表观遗传学调控起到关键作用,主要涉及组蛋白修饰、DNA甲基化、非编码RNA的调控等,不同的表观遗传修饰和机制相互作用,共同调节间充质干细胞成肝分化;(3)在三维培养条件下诱导间充质干细胞成肝分化过程中,表观遗传学修饰尤其是组蛋白乙酰化发挥了重要作用。未来,需要结合表观遗传学优化三维培养策略,提高成肝诱导效率。BACKGROUND:Hepatocyte-like cells induced by mesenchymal stem cells are promising seed cells for liver regeneration or liver tissue engineering.The efficiency of traditional two-dimensional culture for hepatocyte induction is low,and more and more research is focused on three-dimensional culture for inducing hepatocyte differentiation.OBJECTIVE:To summarize three-dimensional culture models for the hepatic induction of mesenchymal stem cells,focus on research progress on the epigenetic regulation mechanisms of mesenchymal stem cell hepatogenic differentiation,providing a theoretical basis for improving the differentiation efficiency of mesenchymal stem cells.METHODS:Relevant articles in the PubMed and other databases such as CNKI were searched,using Chinese and English search terms“mesenchymal stem cell,3D culture,hepatogenic differentiation,hepatocyte-like cells,epigenetics.”Additionally,the literature tracing method was employed to find some of the literature for a comprehensive review and analysis.RESULTS AND CONCLUSION:(1)Common three-dimensional culture models for the hepatogenic differentiation of mesenchymal stem cells currently include spheroids,biological scaffolds,bioprinting,and microfluidic chips.Each of these models has its own advantages and disadvantages in the process of inducing hepatogenic differentiation.(2)During the differentiation of mesenchymal stem cells into hepatocyte-like cells,epigenetic regulation plays a key role,primarily involving histone modification,DNA methylation,and the regulation of non-coding RNAs.(3)Under three-dimensional culture conditions,epigenetic modifications,especially histone acetylation,play an important role in promoting the hepatogenic differentiation of mesenchymal stem cells.

关 键 词：间充质干细胞 三维培养 成肝诱导 肝细胞样细胞 表观遗传学 组蛋白乙酰化 综述 

分 类 号：R458[医药卫生—治疗学] R363[医药卫生—临床医学] R329.2