Interaction of hepatocytes and pancreatic islets cotransplanted in polymeric matrices

Heterotopic hepatocyte transplantation (HcTx) in polymeric matrices may become an alternative to liver transplantation for metabolic disorders. Hepatotrophic stimulation by means of a portocaval shunt operation is an established, but invasive, procedure used to optimize hepatocyte engraftment in matrices. 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. HcTx and ICT were compared with HcTx plus portocaval shunt and HcTx without stimulation. Matrices were investigated at 1, 3, and 6 months after implantation: the test methods applied were trichrome staining, PAS, immunohistochemistry for insulin, glucagon and incorporated BrdU, and in situ hybridization for albumin RNA. Hepatocytes expressed albumin RNA and formed conglomerates without atypias in all animals. ICT and portocaval shunting increased the number of hepatocytes and BrdU uptake. Alpha cells migrated into the islet-surrounding hepatocytes, whereas beta cells remained immobile. It is concluded that ICT and portocaval shunting supported engraftment of hepatocytes in polymeric matrices equally well. ICT did not interfere with recipient glucose metabolism and did not induce hyperproliferative premalignant foci within the transplanted hepatocytes. The technique is an attractive approach to hepatotrophic stimulation of bioartificial liver equivalents.