title: Mesenchymal Stem Cells with Enhanced Bcl-2 Expression Promote Liver Recovery in a Rat Model of Hepatic Cirrhosis.
abstract: OBJECTIVE
  Mesenchymal stem cell (MSC) transplantation has emerged as an option for the treatment of chronic hepatic cirrhosis, while its therapeutic efficacy could be improved. The bcl-2 gene is anti-apoptotic and can help cell survival and proliferation. Therefore, we explored whether transplanted MSCs with enhanced bcl-2 expression may be beneficial in the treatment of experimental cirrhosis in rats.
  
  
  METHODS
  MSCs were isolated from rat bone marrow, expanded in vitro and transfected with adeno-associated virus (AAV) engineered the bcl-2 gene (AAV-bcl-2). Rats with cirrhosis induced by carbon tetrachloride (CCl4) were treated with AAV-bcl-2 infected BMSCs-AAV-bcl-2, with the cells traced in vivo post transplantation. Liver pathology and function were evaluated 7, 14, 21, and 28 days post transplantation, respectively.
  
  
  RESULTS
  On day 7 post transplantation, the infused AAV-bcl-2 had integrated into the hepatocyte-like cells (HLCs) that expressed albumin (ALB), Cytokeratin 18 (CK18), and hepatocytes nuclear factor 4a (HNF4a). On day 28 post transplantation, rats in the cirrhosis + BMSCs-AAV-bcl-2 group showed the most dense HLCs, highest mRNA and protein levels of ALB, CK18, and HNF4a, compared to the other groups. Their liver function recovered most rapidly in 4 week observation, while histological sign of cirrhosis remained at the end of this period.
  
  
  CONCLUSIONS
  BMSCs over expressing bcl-2 gene showed better survival, and enhanced the differentiation into hepatocytes-like cells, and appeared to promote the recovery of liver function in rats with experimental cirrhosis.
authors.affiliation: Department of Gastrointestinal and Hepatology, The Second Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Shizhu
authors.initials: S
authors.lastname: Jin
authors.forename: Hulun
authors.initials: H
authors.lastname: Li
authors.forename: Mingzi
authors.initials: M
authors.lastname: Han
authors.forename: Mengting
authors.initials: M
authors.lastname: Ruan
authors.forename: Zishuai
authors.initials: Z
authors.lastname: Liu
authors.forename: Feifei
authors.initials: F
authors.lastname: Zhang
authors.forename: Chunwei
authors.initials: C
authors.lastname: Zhang
authors.forename: Yongsub
authors.initials: Y
authors.lastname: Choi
authors.forename: Bingrong
authors.initials: B
authors.lastname: Liu
mesh_terms: D000818:Animals; D000941:Antigens / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D002251:Carbon Tetrachloride; D048430:Cell Shape; D004195:Disease Models, Animal; D015870:Gene Expression; D017930:Genes, Reporter; D022781:Hepatocytes / Q000378:metabolism; D008106:Liver Cirrhosis, Experimental / Q000097:blood / Q000139:chemically induced / Q000378:metabolism / Q000628:therapy*; D008115:Liver Regeneration; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D010641:Phenotype; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results
chemical_list: D000941:Antigens; D015415:Biomarkers; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D002251:Carbon Tetrachloride