Interaction of hepatocytes and pancreatic islets cotransplanted in polymeric matrices

Heterotopic hepatocyte transplantation (HcTx) in polymeric matrices may bec ome an alternative to liver transplantation for metabolic disorders. Hepato trophic stimulation by means of a portocaval shunt operation is an establis hed, but invasive, procedure used to optimize hepatocyte engraftment in mat rices. We evaluated hepatocyte and pancreatic islet cotransplantation (ICT) as an alternative noninvasive approach to hepatotrophic stimulation. Lewis rats served as donors and recipients. Hepatocytes and islets were isolated using collagenase digestion and seeded into polyvinylalcohol matrices. HcT x and ICT were compared with HcTx plus portocaval shunt and HcTx without st imulation. Matrices were investigated at 1, 3, and 6 months after implantat ion: the test methods applied were trichrome staining, PAS, immunohistochem istry for insulin, glucagon and incorporated BrdU, and in situ hybridizatio n for albumin RNA. Hepatocytes expressed albumin RNA and formed conglomerat es without atypias in all animals. ICT and portocaval shunting increased th e number of hepatocytes and BrdU uptake. Alpha cells migrated into the isle t-surrounding hepatocytes, whereas beta cells remained immobile. It is conc luded that ICT and portocaval shunting supported engraftment of hepatocytes in polymeric matrices equally well. ICT did not interfere with recipient g lucose metabolism and did not induce hyperproliferative premalignant foci w ithin the transplanted hepatocytes. The technique is an attractive approach to hepatotrophic stimulation of bioartificial liver equivalents.