Evaluation of methods of hepatotrophic stimulation in rat heterotopic hepatocyte transplantation using polymers

Background: Hepatocyte transplantation has been studied as an alternative t o organ transplantation; Hepatocyte transplant models should provide suffic ient cell mass for replace; ment function and hepatotrophic stimulation of the transplanted cells in heterotopic locations. Method The authors used three-dimensional porous polyvinyl-alcohol matrices as cell carriers, which were implanted between mesenteric leaves of the in testine. In this study, different methods were evaluated for hepatotrophic stimulation. Fifty million transplanted hepatocytes (approximately 10% live r mass) were implanted in Lewis rats. We compared 70% partial hepatectomy, portacaval shunt, cotransplantation of enterocytes, cotransplantation of is lets of Langerhans, and methylprednisolone injection to a control group wit h only hepatocyte transplantation. Portacaval shunt and islet cotransplanta tion also were used in combination. Specimens were harvested 2 weeks after transplantation, and area per histological cross section compromised by hep atocytes was measured. Results: Seventy percent partial hepatectomy, enterocyte cotransplantation, and methylprednisolone injection resulted in hepatocyte maintenance simila r to control group (3,100 +/- 7,592 mu m(2)). Portacaval shunt (96,866 +/- 55,039 mu m(2)) and islet cotransplantation (173,020 +/- 75,977 mu m(2)) yi elded a highly significant increase in hepatocyte area. The combination of portacaval shunt and islet cotransplantation resulted in a significant incr ease compared with using these methods individually (288,930 +/- 86,726 mu m(2)). Additional immunohistochemical stains for active DNA synthesis, insu lin, and glucagon demonstrated the proliferative abilities of the hepatocyt es and the synthesis of insulin and glucagon in the cotransplanted islets. Conclusion: Hepatocyte transplantation can be performed using polymer carri ers and that hepatocyte survival and maintenance can be improved with porta caval shunt and islet cotransplantation. J Pediatr Surg 34 1118-1123. Copyr ight (C) 1999 by W.B. Saunders Company.