title: Liver Anti-Fibrosis Therapy with Mesenchymal Stem Cells Secreting Hepatocyte Growth Factor.
abstract: The objective of this study is to investigate the anti-fibrotic effect of combined mesencymal stem cells (MSCs) and gene therapy on liver fibrosis. When transfected by the complex with a plasmid DNA of hepatocyte growth factor (HGF) and the spermine-introduced pullulan of gene carrier, MSCs secreted HGF protein over 1 week. The HGF secreted from transfected MSC had the biological activity to promote the albumin production of hepatocytes. After intravenous injection, the HGF-secreting MSCs (HGF-MSC) accumulated in the liver. The injection of HGF-MSC decreased the fibrosis area in a rat model of liver fibrosis to a significantly great extent compared with that of original MSC. In the in vitro experiment, the higher number of HGF-transfected MSCs was migrated by stromal cell-derived factor (SDF)-1α more strongly than the original MSC. Considering the promotion of SDF-1α secretion in the liver fibrosis, it is possible that, when transplanted, genetically-engineered MSCs are accumulated in the liver due to their higher response to SDF-1α. It is concluded that the intravenous injection of genetically-engineered MSCs is a promising therapy for liver fibrosis.
authors.affiliation: a Department of Biomaterials , Institute for Frontier Medical Sciences, Kyoto University , 53 Kawara-cho Shogoin , Sakyo-ku , Kyoto , 606-8507 , Japan.
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Ishikawa
authors.forename: Jun-Ichiro
authors.initials: J
authors.lastname: Jo
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tabata
mesh_terms: D000818:Animals; D005818:Genetic Engineering; D015316:Genetic Therapy; D005936:Glucans / Q000737:chemistry; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics* / Q000628:therapy*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D010957:Plasmids / Q000737:chemistry / Q000235:genetics; D051381:Rats; D013096:Spermine / Q000737:chemistry; D014162:Transfection
chemical_list: D005936:Glucans; D013096:Spermine; D017228:Hepatocyte Growth Factor; C009109:pullulan