Angiogenic cell therapy for hepatic fibrosis

Progression of liver fibrosis has been linked with injuries associated with hypoxia and neovascularization. Neovascularization consists of angiogenesis and vasculogenesis, representing formation of blood vessels by differentiation of endothelial progenitor cells (EPCs). We investigated antifibrogenic and regenerative effects of EPC transplantation in chronic liver injury. Rat EPCs were isolated from bone marrow cells and examined in vitro for lineage markers. Recipient rats were injected intraperitoneally with dimethylnitrosamine (DMN) three times weekly for 4 weeks, plus EPC transplantation once weekly for 4 weeks. Transplanted rats showed suppression of liver fibrogenesis. Expression of growth factors promoting liver regeneration such as hepatocyte growth factor (HGF), transforming growth factor (TGF)-alpha, epidermal growth factor (EGF), and vascular endothelial growth factor (VEGF) was increased in transplanted rats, together with hepatocyte proliferation. Normal liver function parameters such as transaminase, total bilirubin, total protein, and albumin were maintained in transplanted rats. EPC transplantation is effective not only for preventing liver fibrosis but also for promoting regeneration in chronically damaged livers. Also, recently it has been reported that green fluorescent protein-positive bone marrow cells contribute to the liver tissue repair of fibrosis model rats. EPC transplantation might become an alternative if further preclinical investigation finds it to be effective in severely cirrhotic livers.