Survival and functions of encapsulated porcine hepatocytes after allotransplantation or xenotransplantation without immunosuppression

Background. This study evaluated the survival and functions of encapsulated porcine hepatocytes after intraperitoneal allotransplantation and xenotran splantation without immunosuppression. Methods. Isolated porcine hepatocytes were encapsulated in AN 69 polymer ca psules (45.10(6)/capsule) and transplanted intraperitoneally in 12 rats and 22 pigs. Fifteen, 30 and 60 days after transplantation, capsules were remo ved and the viability and morphology: of explanted hepatocytes were examine d under light and electronic microscopy. The potential to produce albumin w as assessed by evaluating the level of albumin messenger RNA, using semiqua ntitative reverse transcription-polymerase chain reaction. 6 beta -Hydroxyl ase activity was measured by high-performance liquid chromatography. In add ition, cytochrome P450 3A proteins were detected by Western blot only In al logeneic hepatocytes. Results. Similar results were observed after allotransplantation and xenotr ansplantation. Histologic studies showed that hepatocytes were well-preserv ed and arranged in cords for up to 30 days. The expression of porcine album in gene was maintained up to 15 days. 6 beta -Hydroxylase activity was 2.5- fold lower at day 15 than in freshly encapsulated hepatocytes, which were n ot transplanted. In allogeneic hepatocytes, the expression of CYP 3A, prote in was detected up to 60 days after transplantation. Conclusions. Encapsulated porcine hepatocytes remain viable and functional for at least 15 days after allotransplantation and xenotransplantation with out immunosuppression. The demonstration of maintained hepatic functions in transplanted porcine hepatocytes up to 15 days is a first step toward appl ication in the treatment of acute liver failure.