EXPANSION OF DONOR HEPATOCYTES AFTER RECOMBINANT ADENOVIRUS-INDUCED LIVER-REGENERATION IN MICE

Hepatocyte transplantation is a potential form of therapy for patients with genetic hepatodeficiency disorders. Unfortunately, hepatocellula r transplantation has been limited because of the relatively low numbe rs of donor cells that can ultimately take up residence in the host li ver. To give the donor cells a proliferative stimulus, a recombinant a denovirus vector that expresses a nonsecreted urokinase (urokinase-typ e plasminogen activator) was transduced into the livers of recipient a nimals before transplantation. Because urokinase production in hepatoc ytes causes the slow turnover of hepatocytes, 2 days after adenovirus- mediated gene transfer into the livers of recipient mice, 2 X 10(6) co ngenic donor cells tagged with beta-galactosidase (beta-Gal) reporter were implanted via the portal vein. As a result, on average, 8.6% of t he recipient hepatocytes in the livers were derived from donor cells-a 20-fold increase compared with control animals in which no proliferat ive stimulus was present.