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Embolization of Portal Vein Branches Induces Hepatocyte Replication in Swine: A Potential Step in Hepatic Gene Therapy

¹ Mallinckrodt Institute of Radiology (J.R.D., M.E.H.)
² Depts of Cell Biology and Physiology (J.R.D.)
³ Internal Medicine (S.R.C.), Washington Univ School of Medicine, St Louis, Mo
⁴ Depts of Biochemistry and Molecular Biophysics (S.R.C., K.P.P.)
⁵ Pathology (E.M.B.), St Louis Univ Medical School, Mo.

PURPOSE: To determine whether embolization of portal vein branches would stimulate hepatocyte replication in pigs.

MATERIALS AND METHODS: The portal vein branches supplying 50%–70% of the liver were embolized in eight pigs by using a combination of coils and polyvinyl alcohol particles. The extent of embolization was assessed at portography in all animals and at computed tomography in one animal. Hepatocyte replication was determined by calculating the percentage of cells that incorporated bromodeoxyuridine into their nuclei. Animals survived up to 35 days after the procedure.

RESULTS: Embolization of the portal vein branches supplying the left and median lobes caused transient increases of less than 70% in portal vein pressures and of less than 100% in liver enzyme levels. Indocyanine green clearance was measured in two animals and decreased less than 50%. The percentage of replicating hepatocytes in the nonembolized lobe was 0% on day 0, 7% on day 2, 14% on day 7, and 2% on day 12.

CONCLUSION: Substantial hepatocyte replication occurred 2–7 days after embolization of portal vein branches. Further research will help determine if this procedure can facilitate retroviral transduction in large animals. If successful, the low morbidity of this method may allow its use in humans for gene therapy.

Index terms: Animals • Genes and genetics • Liver, function, 761.91, 761.99 • Portal vein, therapeutic blockade, 957.1264

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