Prolonged function of extra-corporeal perfused hDAF transgenic pig livers with human blood
Introduction The development of genetically modified pigs has renewed interest in the use of porcine liver perfusion in the treatment of acute liver failure.
Materials and methods A previously developed model of extracorporeal perfusion has been used to test the function of porcine livers transgenic for human decay accelerating factor when perfused with fresh, whole, human blood. Three experimental groups were studied: alloperfusions (normal pig livers perfused with pig blood) and xenoperfusions of both unmodified and transgenic pig livers with human blood. All livers were perfused for up to 72 h.
Results Alloperfusion resulted in the maintenance of good function and histological structure. Stable hemodynamic, synthetic and metabolic parameters were demonstrated in both unmodified and transgenic liver xenoperfusions; hyperacute rejection was not seen. In both groups, however, the measured parameters of liver function deteriorated towards the end of the 72 h perfusion period; deterioration was more marked in the non-transgenic group. Xenoperfusions were characterized by a progressive and marked decrease in haematocrit of the circulating blood. Histologically, patchy necrosis was noted in both groups and more retained erythrocytes were seen in the sinusoids of non-transgenic livers, but no other consistent differences were apparent.
Conclusions These studies have demonstrated that porcine liver xenoperfusions can be performed for prolonged periods whilst maintaining good liver function. The use of organs from animals transgenic for a human complement regulator protein confers improvement in some measures of liver function. This preclinical model provides evidence that extra-corporeal liver xenoperfusion may be effective in temporary liver support for patients in acute liver failure.