The Role of Hepatotrophic Stimulation in Heterotopic Hepatocyte Transplantation

In the future, the development of methods for transplantation of large hepatocyte numbers could provide an alternative to the established liver and split liver transplantation. The use of three dimensional prevascularized polyvinyl alcohol (PVA) scaffolds have allowed hepatocyte transplantation equivalent to a whole liver mass. This study was designed to determine if a portacaval-shunt (PCS) or a 70% hepatectomy (70% HE) enhanced engraftment and proliferation of transplanted hepatocytes in heterotopic locations.Male Lewis rats served as both donors and recipients, respectively. PVA-sponges were implanted as matrices for the transplanted hepatocytes. Recipient animals were divided into four groups. All groups received transplantation of 5×107 Hepatocytes (HCTx). In addition, group A received 70% HE, group B received a PCS plus 70% HE whereas group D received PCS. Group C as a control, received only HCTx. Quantitative morphometric analysis of hepatocyte area was performed on day 0, 3, 7 and 14 after transplantation. BrdU staining was performed to study DNA-Synthesis in the graft on day 3 and 14.PCS alone and in combination with a partial hepatectomy led to significantly greater cell area one week after transplantation compared to the partial hepatectomy alone. 70% HE resulted in significantly larger cell area than the controls. At two weeks after transplantation, these significant differences persisted with the exception of Group A and C results which were not significantly different. On day 3, BrdU staining revealed a significantly higher DNA synthesis rate in Groups A and B compared to Group C. On day 14, no statistically significant differences in levels of DNA synthesis could be observed.We conclude that hepatocytes can be successfully transplanted into PVA-devices. Engraftment and proliferation can be significantly enhanced by using portacaval shunt and partial hepatectomy as hepatotrophic stimulation.