The fate of autologous hepatocytes transplanted into spleen, pancreas, mesentery, stomach, and small bowel wall in pigs

Abstract

IntroductionTransplantation of the whole or part of the liver iscurrently the only well-established treatment of aspectrum of life-threatening liver diseases, includingacute liver failure, hepatic cirrhosis, and severalinherited metabolic diseases that result from anabsence or deficiency of hepatocyte-derived geneproducts [1]. Due to the shortage of donor organs,several bioartificial liver devices are currently underinvestigation in several centers [2]. Hopefully theywill prove to be effective in supporting patients withliver failure that are on the high urgency waiting-listfor liver transplantation [3]. In the inherited meta-bolic diseases of the liver, transplantation of hepato-cytes obtained from an allogeneic donor liver couldprovide specific liver functions. In addition, trans-plantation of isolated, autologous hepatocytes mayprovide a means for hepatocyte-directed ex vivo genetherapy [1,4].Much work has been done concerning hepatocytetransplantation in rodents, with intraportal andintrasplenic routes producing the best results withrespect to engraftment, function, and cell survival[5]. The optimal site and methods for implantationof isolated hepatocytes in large animals still remainsto be determined, despite its importance for clinicalapplication of hepatocyte transplantation. The aim ofthis study was to examine intra-abdominal, ectopicimplantation sites for hepatocyte transplantation in alarge animal model, i.e. in the pig.Materials and methodsAnimalsNine adult white female pigs were used, weighingbetween 40 and 44 kg. All procedures were approvedby the institutional guidelines of the Animal EthicalCommittee of the University of Amsterdam.After fasting overnight, induction of anesthesia wasachieved with intramuscular administration of keta-mine (10 mg/kg; Nimatec