title: Temporary amelioration of bilirubin conjugation defect in Gunn rats by transplanting conditionally immortalized hepatocytes.
abstract: BACKGROUND
  Conditionally immortalized hepatocytes (CIH) have been used in hepatocyte transplantation as an alternative to primary hepatocytes to cope with the shortage of donor organs. However, CIH are known to undergo apoptosis at body temperature and survive in vivo for a short period. In the present study, we investigated whether CIH function or not and how long their function is maintained in vivo.
  
  
  METHODS
  Various CIH cell lines that were established with temperature-sensitive Simian virus 40 large T antigen were transplanted into the spleen of Gunn rats, which are defective in bilirubin uridine diphosphate glucuronoside transferase (BUGT). Then, we measured biological changes over 3 months.
  
  
  RESULTS
  Serum bilirubin of the syngeneic CIH recipients decreased by 30%, which was maintained for 8 weeks. Thereafter, it began to rise to basal levels. The recipients of allogeneic CIH showed a minor reduction of bilirubin, although this was not statistically significant. However, there was no significant change in the bilirubin level in recipients of BUGT-defective congeneic CIH throughout the study period. Bilirubin monoglucuronides in the bile were not detected in the recipients of BUGT-defective CIH. However, they appeared in recipients of non-defective CIH and made up approximately 41% of total bile pigments.
  
  
  CONCLUSIONS
  Conditionally immortalized hepatocytes expressed hepatocyte function in vivo as well as in vitro, but the function lasted for a couple of months. According to our previous study, the limited functional duration may be related to the inevitable occurrence of apoptosis of these cells at body temperature. These data suggest that CIH can be used in hepatocyte transplantation only for temporary hepatic support.
authors.affiliation: Department of Internal Medicine, Kyung Hee University College of Medicine, no. 1 Hoiki-Dong, Dondaemoon-Ku, Seoul 130-702, Seoul, Korea. kimbh@khmc.or.kr
authors.forename: Byung-Ho
authors.initials: BH
authors.lastname: Kim
authors.forename: Yo Seb
authors.initials: YS
authors.lastname: Han
authors.forename: Seok Ho
authors.initials: SH
authors.lastname: Dong
authors.forename: Hyo Jong
authors.initials: HJ
authors.lastname: Kim
authors.forename: Young Woon
authors.initials: YW
authors.lastname: Chang
authors.forename: Joung Il
authors.initials: JI
authors.lastname: Lee
authors.forename: Rin
authors.initials: R
authors.lastname: Chang
mesh_terms: D000818:Animals; D017209:Apoptosis; D001663:Bilirubin / Q000378:metabolism*; D015153:Blotting, Western; D002460:Cell Line; D002908:Chronic Disease; D014453:Glucuronosyltransferase / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism / Q000637:transplantation*; D017093:Liver Failure / Q000628:therapy; D008297:Male; D051381:Rats; D011911:Rats, Gunn; D013154:Spleen / Q000166:cytology / Q000378:metabolism*; D013696:Temperature
chemical_list: C019787:bilirubin glucuronoside glucuronosyltransferase; D014453:Glucuronosyltransferase; D001663:Bilirubin