title: Therapeutic potential of mesenchymal stem cells overexpressing human forkhead box A2 gene in the regeneration of damaged liver tissues.
abstract: OBJECTIVE
  Although a liver transplantation is considered to be the only effective long-term treatment in many cases of liver diseases, it is limited by a lack of donor organs and immune rejection. As an autologous stem cell approach, this study was conducted to assess whether forkhead box A2 (Foxa2) gene overexpression in bone marrow-derived mesenchymal stem cells (MSC) could protect the liver from hepatic diseases by stimulating tissue regeneration after cell transplantation.
  
  
  METHODS
  Rat MSC (rMSC) were isolated, characterized, and induced to hepatocytes that expressed liver-specific markers. Four different treatments (control [phosphate-buffered saline], rMSC alone, rMSC/pIRES-enhanced green fluorescent protein (EGFP) vector, and rMSC/pIRES-EGFP/human Foxa2) were injected into the spleen of carbon tetrachloride-injured rats. Biochemical and histological analyses on days 30, 60, and 90 post-transplantation were performed to evaluate the therapeutic capacities of MSC overexpressing hFoxa2.
  
  
  RESULTS
  rMSC transfected with hFoxa2 were induced into hepatogenic linage and expressed several liver-specific genes, such as, Foxa2, α-fetoprotein, cytokeratin-18, hepatocyte nuclear factor-1α, and hepatocyte growth factor. A group of animals treated with MSC/hFoxa2 showed significant recovery of liver-specific enzyme expressions to normal levels at the end of the study (90 days). Furthermore, when compared to the fibrotic areas of the samples treated with MSC alone or MSC/vector, the fibrotic area of the samples treated with rMSC/hFoxa2 for 90 days significantly decreased, until they were completely gone.
  
  
  CONCLUSIONS
  Human Foxa2 efficiently promoted the incorporation of MSC into liver grafts, suggesting that hFoxa2 genes could be used for the structural or functional recovery of damaged liver cells.
authors.affiliation: Department of Biotechnology, Korea University, Seoul, Korea.
authors.forename: Jong-Woo
authors.initials: JW
authors.lastname: Cho
authors.forename: Chul-Young
authors.initials: CY
authors.lastname: Lee
authors.forename: Yong
authors.initials: Y
authors.lastname: Ko
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002251:Carbon Tetrachloride; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051542:Hepatocyte Nuclear Factor 3-beta / Q000235:genetics / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation*; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008115:Liver Regeneration; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; C496502:FOXA2 protein, human; C496504:Foxa2 protein, rat; D011993:Recombinant Fusion Proteins; D051542:Hepatocyte Nuclear Factor 3-beta; D002251:Carbon Tetrachloride