SELECTIVE INTRAPORTAL HEPATOCYTE TRANSPLANTATION IN ANALBUMINEMIC ANDGUNN-RATS

Although significant progress has been achieved in isolated hepatocyte transplantation, the optimal site of cell implantation has not yet be en determined. We have developed a novel experimental method of intrap ortal hepatocyte transplantation that allows easy assessment of the mo rphology and function of transplanted hepatocytes. Donor hepatocytes w ere harvested from Sprague-Dawley rats by in situ EDTA/collagenase per fusion. Fifteen recipient Nagase analbuminemic rats (NAR) underwent ca nnulation of the gastroduodenal vein under ether anesthesia. Either th e posterior or anterior liver lobes were selectively infused with cell s by occluding the portal venous supply of the nontransplanted liver l obes. Normal donor hepatocytes (2x10(7)) suspended in normal saline we re infused over 1 min (4 ml). Recipients were treated with cyclosporin e for the duration of the experiment. Plasma albumin levels were deter mined by ELISA, before and at various intervals after transplantation. In NAR rats transplanted with normal hepatocytes, there was a signifi cant (P<0.003) and sustained (12 weeks) increase in plasma albumin lev els. Control NAR rats transplanted with NAR hepatocytes (n=8) showed n o significant changes in plasma albumin levels. Similarly, normal Wist ar hepatocytes were infused intraportally into the posterior lobes of Gunn rats (n=4), which lack the ability to conjugate bilirubin. Pre- a nd posttransplantation bile was collected following bile duct cannulat ion. Bile analysis by HPLC, demonstrated a significant (P=0.04) increa se in the level of bilirubin conjugates following transplantation and a corresponding decrease in total serum bilirubin (P=0.04). Our experi mental data demonstrate that direct selective intraportal infusion of hepatocytes is an effective technique of hepatocyte transplantation in the rat.