Arterialized partial orthotopic liver transplantation in the mouse: a new model and evaluation of the critical liver mass.
The availability of a model of partial orthotopic liver transplantation (OLT) in the mouse would be an important tool for studying injuries associated with transplantation. The goals of this study were three-fold: (1). to develop a model of partial OLT in the mouse, (2). to determine the minimal graft volume in this model, and (3). to define the injury associated with small volume incompatible with animal survival. Putative grafts of 30% and 50% were prepared. Their weight was 30 +/- 5% and 45 +/- 10%, respectively. Subsequently, 30% and 45% syngeneic partial liver grafts were orthotopically transplanted into C57BL/6 mice. Each recipient receiving a 45% graft survived permanently, whereas those receiving only a 30% graft volume died within 2 to 4 days of surgery. Serum transaminase levels normalized in the 45% graft group within 14 days after surgery. In this group, small foci of necrosis and mild steatosis were noted on histology at postoperative day 2, but no abnormalities were noted after 14 days and 100 days. In contrast, recipients who underwent transplantation with a 30% graft volume showed a comparable amount of necrosis and significant microvesicular steatosis in most hepatocytes 2 days after surgery. Hepatocyte proliferation was reduced in this group when compared with animals who underwent transplantation with a 45% graft volume. In conclusion, partial liver transplantation is feasible in the mouse with a critical graft volume ranging between 30% and 45%. Small liver grafts develop massive microvesicular steatosis and impaired regeneration rapidly leading to animal death.