Steatotic liver transplantation in the mouse: a model of primary nonfunction.
BACKGROUND
The number of potential donor organs deemed suboptimal for transplantation because of hepatic steatosis is rising as the obesity rate increases. However, no mouse transplant model has been described within the framework of hepatic steatosis. We describe the development of and our initial experience with a steatotic mouse orthotopic liver transplant model using the ob/ob mouse. This model is technically achievable and functionally mimics primary nonfunction.


METHODS
Adapting techniques of a nonarterialized murine transplant model, C57BL6 ob/ob mice aged 5-7 weeks (26-35 g) and lean controls served as liver donors and recipients. Orthotopic liver transplantation (OLT) was performed using a two-cuff technique at the infrahepatic cava and portal vein. The suprahepatic cava was anastomosed end to end, and the bile duct was stented. The hepatic artery was not reconstructed.


RESULTS
Lean-to-lean OLT was performed with 70% (n = 10) long-term survival. ob/ob-to-age-matched lean recipients had 0% (n = 10) survival because of size discrepancy. ob/ob livers were transplanted to size-matched lean recipients (>3 months old) with short-term survival of 30% (n = 10). These mice survived the operation, awakened, but expired within 24 h. Serum transaminases revealed a significantly higher injury profile in the recipients of the steatotic livers, and histology showed massive centrilobular coagulative necrosis with hemorrhage, the overall picture being that of primary nonfunction.


CONCLUSIONS
This novel use of the ob/ob mouse for OLT provides us with a model for steatotic transplantation with primary nonfunction as the end point and may help to better understand the response of the steatotic liver to the insult of transplantation.
Birsner
Jennifer H
JH
Department of Surgery, Medical University of South Carolina, Charleston, South Carolina, USA.
Wan
Chidan
C
Cheng
Gang
G
Evans
Zachary P
ZP
Polito
Carmen C
CC
Fiorini
Ryan N
RN
Gilbert
Gregory
G
Haines
Julia K
JK
Schmidt
Michael G
MG
Chavin
Kenneth D
KD
D000818:Animals; D005234:Fatty Liver / Q000150:complications* / Q000601:surgery; D006085:Graft Survival / Q000502:physiology*; D008099:Liver / Q000473:pathology*; D017093:Liver Failure / Q000503:physiopathology*; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009336:Necrosis