title: Transplantation of mesenchymal stem cells expressing TIMP-1-shRNA improves hepatic fibrosis in CCl₄-treated rats.
abstract: This study was to investigate the therapeutic effect of intravenous transplantation of TIMP-1-silencing mesenchymal stem cells (MSCs) in a rat model of liver fibrosis. MSCs were transduced with a lentiviral vector expressing tissue inhibitor of metalloproteinase 1 (TIMP-1)-shRNA, and the liver cirrhosis model was established by injection of CCl4 (1 ml/kg body weight twice a week for 4 weeks) in Sprague Dawley rats. The survived 36 rats were randomly divided into 3 groups: control group, MSCs group, and TIMP-1-shRNA group. At 4 weeks after establishment of animal model, 3×10(6) MSCs were intravenously injected. In TIMP-1-shRNA group, MSCs expressing TIMP-1-shRNA were transplanted. Animals were sacrificed 4 weeks later. Blood was collected for the detection of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The livers were harvested for histological examination. At 5 days after transfection, strong fluorescence was detectable in each group. TIMP-1-shRNA group had the lowest TIMP-1 expression. Following MSCs transplantation, serum ALT and AST reduced in rats with hepatic cirrhosis, and histology showed less fibrotic areas and collagens, as compared to control group. These improvements were more obvious in the TIMP-1-shRNA group. Our study indicates that transplantation of MSCs expressing TIMP-1-shRNA is able to inhibit the progression of liver fibrosis and possibly restore the liver function in a rat model.
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Soochow University Suzhou 215006, China ; Department of Gastroenterology, Wuxi No. 2 People's Hospital Wuxi 214002, China.
authors.forename: Yingwei
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: The Stem Cell Research Laboratory, Wuxi Third People's Hospital Wuxi 214041, China.
authors.forename: Zongning
authors.initials: Z
authors.lastname: Miao
authors.affiliation: Department of Gastroenterology, Wuxi No. 2 People's Hospital Wuxi 214002, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Gong
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Soochow University Suzhou 215006, China.
authors.forename: Weichang
authors.initials: W
authors.lastname: Chen
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002251:Carbon Tetrachloride / Q000633:toxicity; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D008106:Liver Cirrhosis, Experimental / Q000473:pathology*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D034741:RNA, Small Interfering; D051381:Rats; D017207:Rats, Sprague-Dawley; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D034741:RNA, Small Interfering; D019715:Tissue Inhibitor of Metalloproteinase-1; D002251:Carbon Tetrachloride
keywords: RNA interference; Tissue inhibitor of matrix metalprotease-1; bone marrow mesenchymal stem cells; liver fibrosis