Temporary amelioration of bilirubin conjugation defect in Gunn rats by transplanting conditionally immortalized hepatocytes.
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.
Kim
Byung-Ho
BH
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
Han
Yo Seb
YS
Dong
Seok Ho
SH
Kim
Hyo Jong
HJ
Chang
Young Woon
YW
Lee
Joung Il
JI
Chang
Rin
R
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
C019787:bilirubin glucuronoside glucuronosyltransferase; D014453:Glucuronosyltransferase; D001663:Bilirubin