β3整合素、miR-122联合修饰肝星状细胞源性exosome以重塑"细胞间通讯网络"对肝纤维化的干预研究

肝星状细胞（hepatic stellate cell, HSC）失去分化表型，以及肝干细胞向肝细胞分化受阻是诱导肝纤维化的关键病理生理机制。近期发现，细胞主动分泌形成的exosome介导了HSC-肝干细胞"细胞间通讯网络"，从而构成两者发生的共同基础。为此，本研究拟采用β3整合素、miR-122联合修饰HSC来源性exosome。借助β3整合素与肝干细胞标志物CD90.1特异性结合，实现HSC-肝干细胞的"靶向细胞间通讯"；并以靶向肝干细胞的exosome为载体，持续进行miR-122的跨细胞转运。由此在重塑"细胞间通讯网络" 的基础上纠正miR-122表达缺失，既恢复HSC的分化表型，又诱导肝干细胞向成熟肝细胞分化。最终通过多途径同步干预，发挥防治肝纤维化的作用。

De-differentiation of hepatic stellate cell (HSCs) and differentiation blockade of liver stem cells reflect the critical pathophysiological mechanisms of liver fibrosis. Exosome, which is secreted by HSCs, has recently been proved to responsible for these pathophysiological disorders by the 'communication network' between HSCs and liver stem cells. We, therefore, attempt to modify the HSC-derived exosomes by both β3 integrin and miR-122. Specific binding of β3 integrin and stem cell marker, CD90.1, results in the targeting communication between HSCs and liver stem cells. Transcellular transportation of miR-122, mainly from HSCs to liver stem cells, is then fulfilled by the fusion of cell membrane and exosome. Reconstruction of 'intercellular communication network' restores the miR-122 level in both HSCs and liver stem cells. It is expected to abolish the de-differentiation phenotype of HSCs, and also induce the differentiation from liver stem cells to hepatocytes. Liver fibrosis may be resultantly inhibited.