ABSTRACT
BACKGROUND: Hepatocyte transplantation could be an alternative to liver transplantation for the treatment of metabolic diseases, however this therapy is still limited by the loss of transplanted cells in the portal radicles before their entry into the sinusoids to engraft. Therefore, we investigated the effect of glyceryl trinitrate on hepatic sinusoids and on the efficacy of cell engraftment in a syngenic mice model. METHODS: We first assessed the effect of GTN portal infusion on the parenchymal spreading of colored microspheres. Hepatocytes transplantation in a syngenic mice model was then performed concomitantly with GTN infusion. The distribution of transplanted hepatocytes and their ultimate engraftment were analysed. RESULTS: After GTN perfusion 27% of microspheres shifted from the portal to the sinusoidal zone. Transplanted hepatocytes distribution changed significantly in the portal and parenchymal zones from respectively 53 +/- 2% and 46.8 +/- 2% in control animals to 32.5 +/- 2.4% and 67.5 +/- 2.4% in GTN-treated animals. At days 7 and 15, we noted a significantly better engraftment in GTN group vs. controls (60 +/- 4 vs. 37 +/- 2 transplanted hepatocytes in 20 fields x 400). CONCLUSIONS: Portal perfusion of GTN improved the access of microspheres and transplanted hepatocytes to the sinusoidal bed and also improved the percentage of cell engraftment in the liver. These results suggest that drug dilatation of portal pedicles prior to transplantation increases the efficiency of hepatocyte grafting.
