IN-VIVO GENE-TRANSFER TO THE HUMAN BILIARY-TRACT

The human biliary tract offers an excellent model for gene transfer st udies for a variety of diseases localized to the liver. The aim of thi s study was to determine ifa viable liver might be employed to study v iral transfection of the human biliary system in order to mimic in viv o human experiments. Using a normal human liver initially procured for transplantation but subsequently found unsuitable, and with an intact biliary free, the hepatic vascular supply was accessed for continuous perfusion. The common and left hepatic biliary system was isolated by balloon catheterization. A replication defective adenoviral vector co ntaining the Escherichia coli beta-galactosidase (lac Z) reporter gene (AdCMVLacZ) was injected into the catheter-isolated left and common b ile duct lumen. Viral exposure to the right duct system was prevented by ligation. The bile duct segments were excised and prepared for enzy matic (X-gal) staining. Intense staining was observed in the biliary e pithelium exposed to the adenoviral vector. No evidence of beta-galact osidase staining was noted in the unexposed biliary mucosa. We report direct transfection of biliary epithelial cells from normal human live r with a recombinant adenovirus, Our data suggest potential therapeuti c applications for gene therapy of hepatobiliary disorders.