Therapy for Liver Regeneration with Autologous Bone Marrrow Cell Transplantation-Basic Research and Clinical Application

Abstract

Treatment of mice with CCl₄ twice a week for 4 weeks developed liver cirrhosis with severe hepatic damage. Then mice were transplanted with bone marrow cells (BMCs) of Green Fluorescent Protein (GFP) mouse continuing treatment with CCl₄ for another 4 weeks. Transplanted GFP-positive BMCs migrated into the peri-portal lesions of the cirrhotic liver. The transplanted GFP-positive BMCs differentiated into hepatoblasts and then differentiated into albumin-producing hepatocytes. The differentiation "niche" induced by persistent liver damage due to continuous CCl₄ injection seems to be an essential factor. BMC transplantation improved liver function, liver fibrosis and the survival rate. These findings strongly support the development of a new cell therapy using autologous BMCs to treat liver cirrhosis patients. Based on the results obtained in basic research using the GFP/CCl₄ model, human trials for the patients with decompensate liver cirrhosis are now undergoing. Almost all cases showed improved liver function and reduced liver fibrosis marker after BMC transplantation without severe side effects.