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

Kaufmann P M, Sano K, Uyama S, Breuer C K, Organ G M, Schloo B L, Kluth D, Vacanti J P

Department of Surgery, University of Hamburg Medical School, Germany.

J Pediatr Surg. 1999 Jul;34(7):1118-23. doi: 10.1016/s0022-3468(99)90580-8.

BACKGROUND

Hepatocyte transplantation has been studied as an alternative to organ transplantation. Hepatocyte transplant models should provide sufficient cell mass for replacement 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 intestine. In this study, different methods were evaluated for hepatotrophic stimulation. Fifty million transplanted hepatocytes (approximately 10% liver mass) were implanted in Lewis rats. We compared 70% partial hepatectomy, portacaval shunt, cotransplantation of enterocytes, cotransplantation of islets of Langerhans, and methylprednisolone injection to a control group with only hepatocyte transplantation. Portacaval shunt and islet cotransplantation also were used in combination. Specimens were harvested 2 weeks after transplantation, and area per histological cross section compromised by hepatocytes was measured.

RESULTS

Seventy percent partial hepatectomy, enterocyte cotransplantation, and methylprednisolone injection resulted in hepatocyte maintenance similar to control group (3,100 +/- 7,592 microm2). Portacaval shunt (96,866 +/- 55,039 microm2) and islet cotransplantation (173,020 +/- 75,977 microm2) yielded a highly significant increase in hepatocyte area. The combination of portacaval shunt and islet cotransplantation resulted in a significant increase compared with using these methods individually (288,930 +/- 86,726 microm2). Additional immunohistochemical stains for active DNA synthesis, insulin, and glucagon demonstrated the proliferative abilities of the hepatocytes and the synthesis of insulin and glucagon in the cotransplanted islets.

CONCLUSION

Hepatocyte transplantation can be performed using polymer carriers and that hepatocyte survival and maintenance can be improved with portacaval shunt and islet cotransplantation.