Stem cell Therapy using Umbilical Cord Blood in Liver Disease

Abstract

Stem cell Therapy using Umbilical Cord Blood in Liver Disease

Park Hwon-Kyum MD

Department of Surgery, Hanyang University, School of Medicine, Seoul, Korea

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. Preliminary experience with clinical hepatocyte transplantation during the past decade has provided proof of concept that cell therapy can be effective for the treatment of some liver diseases. Recent progress in cell biology resulting in the isolation and characterization of hepatic stem cells and progenitor cells further increased the expectation for a new approach to the treatment of genetic and chronic liver disease. The role of stem and progenitor cells in liver regeneration is still not completely defined, but it is now accepted that there are three compartments of cells that can respond to loss of hepatocytes. At a first level, mature hepatocytes, which normally are growth quiescent, account for physiological tissue renewal as well as for liver cell replacement after partial hepatectomy and exposure to toxic chemicals, such as carbon tetrachloride. At a second level, an intrahepatic compartment of progenitor cells is activated when the proliferation of hepatocytes is inhibited, or during extensive and chronic liver disease. These `oval cells` can be seen budding and migrating from the intralobular bile ducts into the liver parenchyma. Oval cells can display phenotypic features of both hepatocytes and biliary epithelial cells and are viewed as bipotent progenitors that can differentiate into hepatocytes and cholangiocytes. Recent data suggest that in addition to mature hepatocytes and oval cells, a third compartment of cells can participate in liver regeneration. Extrahepatic sources, such as bone marrow, umbilical cord blood, and fetal liver, can enter the liver and give rise to hepatocytes and cholangiocytes. At a first glance, these appear to provide exciting new opportunities for cell theratpy as some types of stem cells proliferate efficiently in vitro and therefore may help to generate a larger supply of human hepatocytes or precursor cells for transplantation. It is not yet fully clear how the different stem cell populations interact with both each other and the mature liver cell population to achieve homeostatic cell and differentiation equilibrium in the diseased and/or regenerating organ. In any case, the outstanding growth potential of liver stem cells may become a clinically viable option in the field of cell transplantation. We already reported that the mesenchymal stem cells could be isolated from human umbilical cord blood and the differentiation into muscle, nerve cell, endothelial cell and hepatocyte could be possible. And we tried clinical application after approval of Korean FDA in Buerger`s disease and liver cirrhosis and had the very promising results. Here we report the early results of Umbilical Cord Blood Stem Cell Transplantation for Liver cirrhosis. The general conditions and the laboratory data of the patients changed very positively. And CT volumetry of the treated cirrhotic liver gave us possibility of the cure as we already had the good results of angiography in Buerger`s disease. Transplantation of UCB stem cell for liver cirrhosis is not curative treatment modality at present but seems to be the very effective and safe one in the near future by the basic research of the stem cell and some modification of the purification and culture methods and some development of route of administration of the UCB stem cell.