Lesson from the GFP/CCl4 model--translational research project: the development of cell therapy using autologous bone marrow cells in patients with liver cirrhosis.

The plasticity of bone marrow has been confirmed by the analysis of autopsy findings in female recipients of bone marrow cells transplanted from male donors. To establish new clinical cell therapies using autologous bone marrow cells for patients with liver failure, we developed a new in vivo model, the "green fluorescent protein (GFP)/carbon tetrachloride (CCl(4)) model". Using the GFP/CCl(4) model, we found that transplanted Liv8-negative cells efficiently repopulated into cirrhotic liver tissue and trans-differentiated into albumin-producing hepatocytes under conditions of persistent liver damage induced by CCl(4). Moreover, one marrow cell transplantation into liver cirrhosis mice improved their liver function, ameliorated liver fibrosis, and improved their survival rate. Results from the GFP/CCl(4) model showed that cell therapy using autologous bone marrow cells has the potential to become an effective treatment for patients with liver failure. Here we describe the findings from the GFP/CCl(4) model and the scope of the translational research project.