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.
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
BACKGROUND:Autoimmune hepatitis is a chronic,generally progressive inflammatory disorder of the liver,of which the cause is unclear.It was demonstrated that genetic factors are involved in its pathogenesis.Previous studies showed that human leukocyte antigen in the major histocompatibility complex(MHC) is associated with susceptibility to autoimmune hepatitis.Current genome scanning studies suggest that genes outside the MHC also play a critical role in autoimmune disorders.This article focuses on our current understanding of the polymorphisms of these genes and their roles in the pathogenesis of autoimmune hepatitis.DATA SOURCES:Studies were identified by searching MEDLINE and PubMed for articles using the keywords autoimmune hepatitis,polymorphism,CTLA-4,Fas,TNF-α TGF-β1,TBX21 and VDR up to May 2011.Additional papers were identified by a manual search of the references from key articles.RESULTS:According to the case-control studies on genetic polymorphisms,at least six genes(CTLA-4,Fas,TNF-α TGF-β1,TBX21 and VDR) are involved in autoimmune hepatitis besides HLA.So far,there has been no agreement about gene susceptibility and the actual clinical significance of these genes is still controversial.CONCLUSION:Studies on gene polymorphisms outside the MHC and knowledge of genetic predispositions for autoimmune hepatitis may not only elucidate pathogenic mechanisms,but also provide new targets for therapy in the future.
Jie Tang,Cheng Zhou,Zhi-Jun Zhang and Shu-Sen Zheng Hangzhou,China Key Laboratory of Combined Multi-organ Trans- plantation, Ministry of Public Health, Department of Hepatobiliary and Pancreatic Surgery , and State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
