Adipose-derived mesenchymal stem cells inhibit activation of hepatic stellate cells in vitro and ameliorate rat liver fibrosis in vivo

Abstract

Previous studies suggested that mesenchymal stem cells may ameliorate fibrogenesis through the inhibition of hepatic stellate cells (HSCs) activation. This study aimed to investigate whether adipose derived mesenchymal stem cells (ADSCs) could modulate the activation of HSCs and contribute to the recovery of liver fibrogenesis. Methods: ADSCs and HSCs were isolated from Sprague-Dawley rats and co-cultured using a transwells insert. Cell proliferation, apoptosis and smooth muscle α-actin (α-SMA) expression in HSCs were examined. Rats were injected with CCl4 to induce liver fibrogenesis. After injection of ADSCs through portal vein, the rats were examined for pathological changes in the liver. α-SMA expression and hydroxyproline content in the liver and serum levels of collagen III and hyaluronic acid was detected. Results: After co-culturing for 72 h, the proliferation and activation of HSCs was inhibited by ADSCs and the apoptosis of HSCs was promoted by ADSCs. Transplantation of ADSCs inhibited liver fibrogenesis in the rats. Conclusion: ADSCs inhibit the proliferation and activation of HSCs in vitro and inhibit liver fibrogenesis in rat model, suggesting the potential application of ADSCs in liver fibrogenesis therapy.

Keywords

• adipose derived mesenchymal stem cells
• fibrosis
• hepatic stellate cells
• proliferation