Hepatocyte differentiation of human fibroblasts from cirrhotic liver in vitro and in vivo  

作　　者：Yu-Ling Sun,Sheng-Yong Yin,Lin Zhou,Hai-Yang Xie,Feng Zhang, Li-Ming Wu and Shu-Sen Zheng Key Lab of Hepatobiliary and Pancreatic Surgery,and Digestive Organ Transplantation of Henan Province,Department of Hepatobiliary and Pancreatic Surgery,First Affiliated Hospital,Zhengzhou University School of Medicine,Zhengzhou,China and Key Lab of Combined Multi-organ Transplantation,Ministry of Public Health and Department of Hepatobiliary and Pancreatic Surgery,First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310003, China 

出　　处：《Hepatobiliary & Pancreatic Diseases International》2011年第1期55-63,共9页国际肝胆胰疾病杂志（英文版）

基　　金：supported by grants from the National Basic Research Program of China(2009CB522403);the Program for Changjiang Scholars and Innovative Research Team in University(IRT0753);the National Natural Science Foundation of China(30801327);National Key Scientific and Technological Research program(2008ZX10002-022)

摘　　要：BACKGROUND:Mesenchymal stem cells(MSCs)and fibro-blasts have intimate relationships,and the phenotypic homology between fibroblasts and MSCs has been recently described.The aim of this study was to investigate the hepatic differentiating potential of human fibroblasts in cirrhotic liver. METHODS:The phenotypes of fibroblasts in cirrhotic liver were labeled by biological methods.After that,the differentiation potential of these fibroblasts in vitro was characterized in terms of liver-specific gene and protein expression.Finally,an animal model of hepatocyte regeneration in severe combined immunodeficient(SCID)mice was created by retrorsine injection and partial hepatectomy,and the expression of human hepatocyte proteins in SCID mouse livers was checked by immunohistochemical analysis after fibroblast administration. RESULTS:Surface immunophenotyping revealed that a minority of fibroblasts expressed markers of MSCs and hepatic epithelial cytokeratins as well as alpha-smooth muscle actin, but homogeneously expressed vimentin,desmin,prolyl 4-hydroxylase and fibronectin.These fibroblasts presented the characteristics of hepatocytes in vitro and differentiated directly into functional hepatocytes in the liver of hepatecto-mized SCID mice.CONCLUSIONS:This study demonstrated that fibroblasts in cirrhotic liver have the potential to differentiate into hepatocyte-like cells in vitro and in vivo.Our findings infer that hepatic differentiation of fibroblasts may serve as a new target for reversion of liver fibrosis and a cell source for tissue engineering.BACKGROUND:Mesenchymal stem cells(MSCs)and fibro-blasts have intimate relationships,and the phenotypic homology between fibroblasts and MSCs has been recently described.The aim of this study was to investigate the hepatic differentiating potential of human fibroblasts in cirrhotic liver. METHODS:The phenotypes of fibroblasts in cirrhotic liver were labeled by biological methods.After that,the differentiation potential of these fibroblasts in vitro was characterized in terms of liver-specific gene and protein expression.Finally,an animal model of hepatocyte regeneration in severe combined immunodeficient(SCID)mice was created by retrorsine injection and partial hepatectomy,and the expression of human hepatocyte proteins in SCID mouse livers was checked by immunohistochemical analysis after fibroblast administration. RESULTS:Surface immunophenotyping revealed that a minority of fibroblasts expressed markers of MSCs and hepatic epithelial cytokeratins as well as alpha-smooth muscle actin, but homogeneously expressed vimentin,desmin,prolyl 4-hydroxylase and fibronectin.These fibroblasts presented the characteristics of hepatocytes in vitro and differentiated directly into functional hepatocytes in the liver of hepatecto-mized SCID mice.CONCLUSIONS:This study demonstrated that fibroblasts in cirrhotic liver have the potential to differentiate into hepatocyte-like cells in vitro and in vivo.Our findings infer that hepatic differentiation of fibroblasts may serve as a new target for reversion of liver fibrosis and a cell source for tissue engineering.

关 键 词：FIBROBLASTS HEPATOCYTES mesenchymal-epithelial transition 

分 类 号：R575.2[医药卫生—消化系统]