The development of methods for somatic gene therapy not only challenges the state-of-the-art of molecular biology, but also of surgery. In particular, the proposal that hepatic gene therapy could be performed by harvesting hepatocytes from a patient's genetically defective liver, infecting these cells with viruses carrying a recombinant gene capable of providing the defective gene product, and then returning these cells to the patient's liver is dependent upon the development of surgical techniques for hepatocellular transplantation. While there is an extensive surgical literature on hepatocellular transplantation in animals, this technique has never been attempted in humans. Hepatocellular transplantation would be useful not only as an adjunct procedure for somatic gene therapy, but may provide an attractive alternative to orthotopic liver transplantation in some patients with liver disease secondary to genetic abnormalities. In this proposal we describe experiments aimed at establishing methods for hepatocellular transplantation. We will evaluate optimal conditions for preservation of liver segments prior to hepatocyte isolation; conditions for handling and infusing hepatocytes; surgical approaches to delivering hepatocytes to the liver; and the optimal schedule for administration of hepatocytes.
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