Reduced-size liver transplantation in the mouse

Abstract

Background: Reduced-size liver transplantation (RSLT) is increasingly used but is still associated with an increased susceptibility to graft damage, failure, and retransplantation. To investigate mechanisms underlying graft injury after RSLT, this study developed a model of RSLT in mice.

Methods: Livers from male C57Bl/6 mice were explanted and stored in cold University of Wisconsin solution. The livers were reduced to 50% by resecting the left lobes. After cold storage for 1 hr, the grafts were implanted. As controls, full-size liver transplantations and sham operations were performed. In some mice, after 41 hr of surgery, 5-bromo-2'-deoxyuridine (BrdU) was administered for BrdU cytochemistry and histology 1 hr later. Alanine transaminase, bilirubin, and survival were determined.

Results: Survival after RSLT was 100% and 86% after 42 hr and 8 days, respectively, compared with 100% after full-size transplantation. After 42 hr, alanine transaminase increased eightfold after RSLT and twofold after full-size versus sham operation. Bilirubin in RLST increased approximately twofold compared with full-size and sham. Histology after RSLT was consistent with regeneration but otherwise virtually normal. BrdU incorporation after RSLT and full-size transplantation increased 54-fold and twofold, respectively, compared with sham. Regeneration of the reduced-size graft was also indicated by a 67% increase of graft weight after 42 hr.

Conclusion: RSLT can be performed in mice with good graft survival, minimal graft injury, and a robust hepatic regenerative response. This model of 50% RSLT provides a new tool to study mechanisms of graft injury and regeneration in genetically modified mice.