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: Hidefumi Ishikawa, Jun-Ichiro Jo, Yasuhiko Tabata
• Journal: Journal of biomaterials science. Polymer edition (J Biomater Sci Polym Ed) Vol. 23 Issue 18 Pg. 2259-72 ( 2012) ISSN: 1568-5624 [Electronic] England
• PMID: 22182291 (Publication Type: Journal Article)

Chemical References

• Glucans
• Spermine
• Hepatocyte Growth Factor
• pullulan

Topics

• Animals
• Genetic Engineering
• Genetic Therapy
• Glucans (chemistry)
• Hepatocyte Growth Factor (genetics, metabolism)
• Humans
• Liver Cirrhosis (genetics, therapy)
• Mesenchymal Stem Cell Transplantation
• Mesenchymal Stem Cells (metabolism)
• Plasmids (chemistry, genetics)
• Rats
• Spermine (chemistry)
• Transfection