Intrasplenic transplanted adult rat isolated hepatocyte fraction but not cholangiocytes forms bile canaliculi.
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.
Department of Surgical Research Transplantation and Epigenetics, Medical Research Center, Polish Academy of Science, Warsaw, Poland; Department of Transplantation Surgery, Central Clinical Hospital, Ministry of Internal Affairs, Warsaw, Poland. Electronic address: waldemar.l.olszewski@gmail.com.
W L
WL
Olszewski
Department of Surgical Research Transplantation and Epigenetics, Medical Research Center, Polish Academy of Science, Warsaw, Poland.
A
A
Charysz
Department of Surgical Research Transplantation and Epigenetics, Medical Research Center, Polish Academy of Science, Warsaw, Poland.
M
M
Gewartowska
Theodor Bilharz Research Institute, Giza, Egypt.
M E
ME
Nagui
D000818:Animals; D001648:Bile Canaliculi / Q000378:metabolism*; D003135:Common Bile Duct / Q000378:metabolism; D005260:Female; D022781:Hepatocytes / Q000637:transplantation*; D006801:Humans; D007150:Immunohistochemistry; D008026:Ligation; D017114:Liver Failure, Acute / Q000378:metabolism; D016031:Liver Transplantation; D008875:Middle Aged; D011917:Rats, Inbred Lew; D013154:Spleen / Q000378:metabolism / Q000601:surgery; D005723:gamma-Glutamyltransferase
D005723:gamma-Glutamyltransferase