Transplantation of human amnion-derived mesenchymal stem cells ameliorates carbon tetrachloride-induced liver fibrosis in rats

Aims: Mesenchymal stem cells (MSCs) have been reported to be a valuable cell source in cell therapy. Recently, several studies have shown that MSC can be easily isolated from human amnion, and a large amount of cells can be obtained. We thus examined the effects of transplantation of human amnion-derived MSCs (hAMSCs) in rats with liver fibrosis. Methods: Amnion was obtained at Cesarean delivery, and hAMSCs were isolated and expanded. Liver fibrosis was induced in 6-week-old male Sprague-Dawley rats by intraperitoneal injection of 2 ml/kg of 50% carbon tetrachloride (CCl₄) twice a week for 7 weeks. At 3 weeks, hAMSCs (1x10⁶ cells) were transplanted intravenously. Rats were sacrificed at 7 weeks, and histological analyses and quantitative RT-PCR were performed. Results: Transplantation of hAMSCs significantly reduced the fibrotic area and deposition of type I collagen. In addition, hAMSC transplantation significantly suppressed the activation of hepatic stellite cells and Kupffer cells in the liver of hAMSC-treated rats. mRNA expression of α-SMA was significantly decreased in the liver of hAMSC-treated rats, and the expression of type I collagen, TGF-β and IL-1β tended to be decreased by hAMSC transplantation. Conclusion: Transplantation of hAMSCs provided significant improvement in a rat model of liver fibrosis, possibly through inhibition of inflammatory reaction. AMSC would be considered as a new cell source for the treatment of liver fibrosis.