Use of a pre-clinical pig model to characterize and modulate immune responses following liver cell transplantation (C11*)

目前肝细胞移植的障碍是：(1)缺乏足够数量的肝细胞；(2)同种异体免疫反应的形成，难以监测细胞移植后的排斥反应；(3)缺乏合适的临床前模型将在小鼠身上获得的结果转化为临床应用。因此，新项目C11建立了大肝切除后猪肝细胞移植的模型。在啮齿动物模型中，移植的肝细胞必须重新填充有毒的微环境(例如，在FAH-/-小鼠中)，与此不同，大切除后的肝脏环境更有利于移植细胞的植入。此外，该小组将通过使用肝脏干细胞来解决细胞数量的问题。他们最近建立了一种方案，将肝细胞去分化为干细胞样状态，在这种状态下，细胞可以在体外有效地扩增。

The current obstacles for hepatocyte transplantation are (1) the lack of sufficient numbers of hepatocytes, (2) the development of an allogeneic immune response with the difficulty to monitor rejection after cellular transplantation and (3) the lack of appropriate preclinical models translating the results obtained in mice into clinical applications. Therefore, the new project C11 has established a pig model of hepatocyte transplantation after major hepatic resection. In contrast to the rodent models in which transferred hepatocytes have to repopulate a toxic microenvironment (e.g. in FAH-/- mice), the hepatic environment after major resection will rather facilitate the engraftment of transferred cells. In addition, the group will address the problem of cell number by employing liver stem cells. They recently established a protocol to dedifferentiate hepatocytes into a stem cell like state from which the cells can be efficiently expanded in vitro.