Retroviral-mediated Gene Transfer Into Rat Auxiliary Liver Transplant In Vivo

Auxiliary liver transplantation is theoretically attractive since it avoids the necessity of removing the patient's own liver, the graft can be removed after recovery of the host liver in patients with potentially reversible liver disease without the need of long-term use of immunosuppresive. Unfortunately, the results of clinical auxiliary liver transplantation have been poor. There are several reasons for failure, including rejection, insufficient drainage of hepatic venous blood, and inadequate inflow of portal blood.The development of molecular biology has greatly increased our understanding of genetics, the normal cell functions and the mechanisms that lead to diseases. The next advance will be in the treatment of the disease.Most of the available techniques for gene transfer were already applied to hepatocytes ex vivo. Attempts to retransplant retrovirally transduced hepatocytes back to patients have shown the limits of the ex vivo approach. The obvious alternative would be the development of suitable techniques for gene transfer in vivo.Gene transfer into liver graft holds the potential to modulate immunogenicity, alter the antigraft immune response, and induce the tolerance to graft. In general, the viral vectors are the most efficient means for the transfer of genes into target cells. The replication-defective retroviral vector can stably integrated into host cell genome and can be expressed appropriately without interference with the normal functions of the target cell. The purpose of the study is to establish a novel method of retroviral-mediated gene transfer into auxiliary liver graft in vivo in the rat and examine the feasibility and stability.For the purpose of study of gene transfer, we established a modified model of auxiliary liver transplantation in rats. The graft contained 30% of the donor liver. The inferior vena cava anastomosis was carried out by anastomosing an oblique IVC cuff of...