Human hepatocyte transplantation for acute liver failure: state of the art and analysis of cell sources

Abstract

Liver transplantation is the only treatment available for acute liver failure. However, mortality rates remain high because of the shortage of donor organs. Indeed up to 20% of patients with acute liver failure may survive without transplantation. In the last two decades, research has focused on the development of alternative or supportive measures to deal with acute liver failure; one of the most studied is hepatocyte transplantation, because it is thought that the function of the liver can only be replaced with a biological substrate characterized by functioning liver cells. Hepatocyte transplantation has been successful in many animal models of acute liver failure, although only several clinical attempts have been made in humans with encouraging but not yet convincing results, mainly because of the lack of a reliable source of live liver cells. Allogenic and xenogenic fresh or cryopreserved hepatocytes have been tested. Recent research has focused on fetal hepatocytes and progenitor liver cells of both hepatic and bone marrow origin. The ability to preserve and bank human hepatocytes would allow pooling of cells from multiple donors to increase the numbers for transplantation. The development of a reliable and large-scale available source of live liver cells would probably have a major impact on the introduction of hepatocyte transplantation in clinical practice.