骨髓间充质干细胞诱导分化为肝细胞的方法及机制研究与进展

Methods of bone marrow mesenchymal stem cells differentiating into hepatocytes and the underlying mechanisms

背景:已有多项研究证明骨髓间充质干细胞可以跨胚层分化为肝细胞,其向肝细胞定向诱导分化的方案很多,但其具体的分子机制目前尚不清楚。目的:综述骨髓间充质干细胞诱导分化为肝细胞的方案及分化机制。方法:检索CNKI数据库、维普、万方和Pub Med数据库2004至2015年期间关于骨髓间充质干细胞向肝细胞分化的文章。检索词分别为"肝细胞(肝样细胞),骨髓间充质干细胞,诱导分化"和"hepatocyte(-like)cells,bone marrow mesenchymal stem cells,differentiation"。最后选择62篇文章纳入结果分析。结果与结论:骨髓间充质干细胞诱导分化为肝细胞的方案很多,但其具体的分化机制仍不甚清楚,目前国内外研究较多的主要有Notch信号通路、Wnt/β-catenin信号通路、P38信号通路、miR-122及钙离子的影响等;骨髓间充质干细胞定向分化的成熟肝细胞为肝细胞移植和人工肝提供了理想的细胞来源,从而使肝细胞移植和人工肝运用于临床治疗终末期肝病提供了新的策略。

BACKGROUND：A number of studies have shown that there are many inducible methods by which bone marrow mesenchymal stem cel s can differentiate into hepatocytes, but the specific molecular mechanism is unclear yet. OBJECTIVE：To review the programs and underlying mechanisms by which bone marrow mesenchymal stem cel s differentiate into hepatocytes. METHODS：A computer-based online search of CNKI, VIP, WanFang and PubMed databases was performed to retrieve articles about directional differentiation of bone marrow mesenchymal stem cel s into hepatocytes published between 2004 and 2015. The key words were“hepatocyte （-like） cel s, bone marrow mesenchymal stem cel s, differentiation”in Chinese and English, respectively. Final y, 62 articles were included in result analysis. RESULTS AND CONCLUSION：There are many programs for hepatic differentiation of bone marrow mesenchymal stem cel s, but the specific molecular mechanism is stil unclear. Many studies mainly focus on Notch signaling pathway, Wnt/β-catenin signaling pathway, P38 signal pathway, miR-122 and effect of calcium ions. Bone marrow mesenchymal stem cel s that can be induced to differentiate into mature hepatocytes provide an ideal cel ular source for hepatocyte transplantation and artificial liver, which is proposed to be a new strategy for clinical treatment of end-stage liver disease.