Cell therapy with bone marrow cell for liver cirrhosis

Abstract

The transplanted GFP-positive BMCs (especially the Liv8 negative cell population, without culturing) migrated into the peri-portal regions of the cirrhotic liver. They differentiated into Liv2-positive hepatoblasts and then into albumin-producing hepatocytes. The differentiation “niche” induced by persistent liver damage due to continuous CCl4 injection seems to be an essential factor. Microarry-SOM analysis showed that at an early stage after BMC transplantation, the genes related to morphology were activated. Then later, genes associated with liver metabolism were activated. Finally, 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, because BMC transplantation itself is an established treatment for hematological diseases. Our finding indicates that FGF2 will accelerate the differentiation of BMC to hepatocyte.Based on the results obtained in basic research using the GFP/CCl4 model, human trials are now undergoing.