Intrasplenic transplantation of syngenic hepatocytes modified by IFN-γ gene ameliorates hepatic fibrosis in rats

Transplanted hepatocytes are ideal carriers for exogenous genes in liver gene therapy. The present study investigated the antifibrogenic effects of intrasplenically transplanted hepatocytes modified with interferon gamma (IFN-γ) gene on cirrhotic rats. Hepatocytes isolated from normal Sprague-Dawley (SD) rats were transfected with an adenoviral vector encoding human IFN-γ gene (AdCMVhIFN-γ) and transplanted into the spleens of syngenic recipients with ongoing liver fibrosis induced by carbon tetrachloride (CCl4). Histology was assessed, and liver hydroxyproline was detected. Additionally, serum procollagen type III (PIIINP) levels and hepatic collagenase activity were measured to determine hepatic collagen synthesis and degradation. Transplantation with AdCMVhIFN-γ transfected hepatocytes ameliorated the histological outcome of liver fibrosis by reducing liver collagen content and decreasing hepatic hydroxyproline. Additionally, IFN-γ transfected hepatocytes reduced serum PIIINP levels and increased hepatic collagenase activity. Our data suggest that transplantation of IFN-γ transfected hepatocytes may reduce the pace of liver fibrosis by inhibiting the synthesis and enhancing the degradation of hepatic collagen.