间充质干细胞在肝纤维化形成中的作用

Mesenchymal stem cells contribute to the formation of liver fibrosis

目的:肌成纤维细胞在肝纤维化形成中起着关键作用。有报道骨髓间充质干细胞可分化为肌成纤维细胞,并迁徙至损伤器官参与其纤维化形成过程。因此,本研究拟探讨骨髓间充质干细胞在肝纤维化形成中的可能作用及机制。方法:(1)以携带增强型绿色荧光蛋白(eGFP)的重组逆转录病毒感染大鼠间充质干细胞株(MSCs)Ap8c3进行标记(Ap8c3-eGFP)。(2)制作胆总管结扎(BDL)及猪血清腹腔注射(IPS)诱导的大鼠肝纤维化动物模型。(3)经大鼠尾静脉将Ap8c3-eGFP注入前述动物体内。(4)检测大鼠肝脏、骨髓中eGFP阳性(eGFP+)细胞分布及表达α平滑肌肌动蛋白(α-SMA)情况。结果:(1)静脉注射的Ap8c3-eGFP干细胞最终可出现于发生肝纤维化的大鼠肝脏及骨髓中。(2)大鼠肝脏中的eGFP+细胞同时表达α-SMA,主要分布于肝脏增生纤维束内。(3)迁徙至骨髓的Ap8c3-eGFP细胞可分化为肌成纤维细胞,表达α-SMA。结论:间充质干细胞可分化为肌成纤维细胞,在肝纤维化形成中起重要作用。

AIM： Myofibroblasts play key roles in the formation of liver fibrosis.It has been reported that bone marrow mesenchymal stem cells can differentiate into myofibroblasts,and migrate to the damaged organs to participate the fibrotic process.Therefore,this study was designed to investigate the possible function and mechanism of bone marrow mesenchymal stem cells in developing liver fibrosis.METHODS： A mesenchymal stem cell line Ap8c3 was tagged with enhanced green fluorescent protein（eGFP）（Ap8c3-eGFP）.The rat model of liver fibrosis was established by bile duct ligation（BDL） or injection of pig serum（IPS）.Ap8c3-eGFP was intravenously injected into BDL or IPS-induced liver fibrotic rats.The eGFP positive（eGFP＋） cells and expression of α-smooth muscle actin（α-SMA） in these eGFP＋ cells in rat livers and bone marrow（BM） were detected.RESULTS： Intravenous engraftment of Ap8c3-eGFP resulted in homing to fibrotic livers as well as BM.Co-expression of α-SMA by eGFP＋ cells was found in liver sections,and eGFP＋ cells were found mainly in fibrotic septum in fibrotic livers.Ap8c3-eGFP was observed to differentiate into myofibroblasts,which specifically expressed α-SMA after homing to bone marrow.CONCLUSION： Differentiation of mesenchymal stem cells into myofibroblasts plays important roles in the formation of liver fibrosis.BM-derived myofibroblasts can migrate to damaged livers and participate in the formation of liver fibrosis.