Intrasplenic Transplanted Adult Rat Isolated Hepatocyte Fraction But Not Cholangiocytes Forms Bile Canaliculi

Abstract Background Hepatocyte transplantation (HT) has been performed in patients with liver-based metabolic disease and acute liver failure as a potential alternative to liver transplantation in countries in which ethical regulations do not allow organ transplantation. One of the problems remains that substances normally secreted by the surviving hepatocytes to bile cannot be removed because of lack of bile canaliculi. We found that ligation of the recipient's common bile duct in hepatocyte transplantation recipients is followed by formation of bile canaliculi. The question arose as to whether the signal released from the obstructed bile vasculature activated the transplanted hepatocytes (HC) or cholangiocyte (CH) to form bile canaliculi. Methods We transplanted separately isolated autologous HC and CH to spleens and observed the structural organization of the grafted cells. Results HC formed glycogen-rich clusters but not cords usually not attached to the CH of the new bile canaliculi. Separate clusters of bile canaliculi with keratin 7 and 19–positive and gamma-glutamyl transpeptidase–positive cells were observed. Transplanted CH remained keratin 7 and 19–positive and gamma-glutamyl transpeptidase positive but did not form canaliculi. Conclusions The transplanted HC fraction may contain hepatic progenitor cells for cholangiocytes, but they become activated only under the condition of bile stasis by an as-yet undefined factor.