Journey from hepatocyte transplantation to hepatic stem cells: a novel treatment strategy for liver diseases.

ABSTRACT

Acute liver failure (ALF) carries high morbidity and mortality (>80%) even in the best centres. Orthotopic liver transplantation (OLTx) is the only viable approach to the treatment of ALF. This has significantly improved the survival in these patients. The major limitations of OLTx are non availability of the donor liver, requirement of a major surgical procedure, high cost and longterm immunosuppression. Isolated hepatocyte transplantation is emerging as an appealing method for the treatment of ALF because of its technical simplicity and easy availability of cells. Transplantation of allogenic/xenogenic hepatocytes transplantation in experimentally induced ALF has shown an increased survival rate. Clinical studies in acute, chronic liver failure and metabolic disorders have also been undertaken in a few centres and have shown encouraging results. To maintain the continuous supply of cells, xenogenic source of hepatocytes (porcine, rabbit, canine) have offered a hope. A major concern regarding the use of xenogenic donors is the risk of transmission of zoonosis and immunogenicity. Recently, Porcine endogenous retrovirus (PERV) has been shown to infect human tissue in vitro. The problem of immunogenicity of xenogenic hepatocytes can be overcome to some extent by immunoisolation, encapsulation technique, which may also provide protection to the hepatocytes during cryopreservation. The knowledge of adult hepatic stem from tissue offered a new hope for the treatment of various chronic and metabolic diseases. Further, the transdifferentiation potentiality of haematopoietic stem cells to hepatic lineage has strengthened cell therapy.