Effect of different liver resection methods on liver damage and regeneration factors VEGF and FGF-2 in mice

Several rodent models for hepatic resection to investigate liver regeneration and repair after liver injury, as well as cell cycle dynamics, have so far been established.1–4 The availability of multiple strains of genetically engineered mice has shifted the focus from the rat toward the murine model.2 In 1931, Higgins and Anderson5 described the classic rodent model for hepatic regeneration in rats in which 2 of 4 liver lobes, about two-thirds of the rat liver, were removed. This approach, however, is not feasible in mice since the rat liver is composed of 4 lobes, whereas the murine liver contains 7 lobes.6,7 Liver resection in mice is technically more demanding than resections in rats because of liver size, tissue texture and the lack of invasive monitoring.6 Presently, extended hepatic resections in mice are generally not yet performed in a standardized fashion, and therefore such studies in mice are systematically biased. The real extent of resection with removal of functioning parenchyma is of importance because of a different regeneration stimulus and potency of the remaining liver.2,4 Nevertheless, numerous groups1,8–10 conducting murine studies still use modifications of the technique originally described by Higgins and Anderson for rats, meaning the resection of the 2 left lateral lobes of the liver, thus mistakenly implying the same amount of resected tissue as in rats. We conducted the present study to investigate the effect of different liver resection models on liver damage and regeneration parameters in mice and help establish a safe, reproducible and extended hepatectomy (70% liver weight). This facilitates standardized regeneration analysis. Furthermore, Sato and colleagues11 showed the importance of the mitogenic growth factors FGF-2 and VEGF, in hepatic regeneration.