Liver irradiation: A potential preparative regimen for hepatocyte transplantation

Advances in the understanding of hepatocyte engraftment and repopulation of the host liver have already led to the use of hepatocyte transplantation ( HT) with some success in the treatment of inherited and acquired liver dise ases. Wider application of HT is severely limited by the unavailability of large number of transplantable hepatocytes and difficulties associated with transplanting an adequate number of cells for achieving therapeutically sa tisfactory levels of metabolic correction. Therefore, there is a need for p reparative regimens that provide a growth advantage to the transplanted (he althy) hepatocytes over the host's own (diseased) hepatocytes so that the f ormer ran repopulate the host liver. We have recently shown that when the l iver of recipient rats was subjected to radiotherapy and partial hepatectom y before HT, the transplanted hepatocytes engrafted in and massively repopu lated the liver, and also ameliorated the adverse clinical and histopatholo gical changes associated with hepatic irradiation. This protocol was then u sed as a preparative regimen for transplanting normal hepatocytes into jaun dice mutant rats (Gunn strain), which lack hepatic bilirubin-uridinediphosp hoglucuronate glucuronosyltransferase and is a model of Crigler-Najjar synd rome Type I. The results showed long-term correction of the metabolic abnor mality, suggesting that the transplanted hepatocytes repopulated an irradia ted liver and were metabolically functional. This strategy could be useful in the treatment of various genetic, metabolic, or malignant diseases of th e liver. (C) 2001 Elsevier Science Inc.