Efficacy of human umbilical cord blood-derived multipotent stem cells in liver cirrhosis of rats and humans

Abstract

EFFICACY OF HUMAN UMBILICAL CORD-DERIVED MULTIPOTENT STEM CELL IN LIVER CIRRHOSIS OF RATS AND HUMAN

BACKGROUND: Liver transplantation is the accepted method of treatment for end stage liver disease. Development of various immunosuppressive drugs and advances in the surgical techniques have led to the improvement in patient and graft survival. However, cell-based therapies are emerging as an alternative to whole-organ transplantation because whole liver transplantations in human beings far outweighs the supply. From the clinical point of view, transplantation of hepatocytes or hepatocyte-like cells may represent an alternatives to orthotopic liver transplants in acute liver failure, for the correction of genetic disorders resulting in metabolically deficient states, and for the late stage liver disease such as cirrhosis. AIMS : We want to find out the efficacy of human umbilical cord-blood derived multipotent stem cells(HUCB MSCs) in the liver cirrhosis of rats induced with CCl4 and 6 patients. Methods : We already demonstrated in vitro differentiation of HUCB MSCs into hepatocyte-like cells. We made the animal model of cirrhosis with CCl4 in Sprague-Dawley rats for 8 weeks. We transplanted HUCB MSCs into the cirrhotic rats at 8 weeks in amount of one million cells labled with CM-Dil, a fluorescent lipophilic probe. We had clinical trial of 6 cirrhotic patients, 3 hepatitis B, 1 hepatitis C, 1 biliary cirrhosis and 1 α1-antitrypsin deficiency. We transplanted HUCB MSCs more than one million cells under the laparoscopy. RESULTS : HUCB MSCs infusion ameliorated various biochemical markers related with liver function. In immunohistochemistry, RT-PCR, and Western blot, fibrosis markers, such as TGF-β1, collagen type I, and -SMA, were also decreased by HUCB-derived MSCs infusion. Early results of 6 cases of HUCB MSCs transplantation in Liver Cirrhosis were very promising. CONCLUSION : These results suggest that HUCB MSCs infusion could not only inhibit the fibrosis formation but also halt the progression of CCl4-induced liver cirrhosis in rats. There has not been any side effect in these patients. HUCB MSCs transplantation in Liver Cirrhosis is not the only curative Treatment method at present but can be one of effective Treatment modalities in patients with acute & chronic liver disease.