Analysis of the growth- and differentiation potential of conditioned, adult hepatocytes versus hepatic precursor cells as an effective means of repopulation of the liver in the rat model

初步临床结果表明，肝细胞移植是治疗严重慢性肝病的一种合适方法。供体肝细胞融入实质和受体器官再生的机制目前还不清楚。成人肝细胞只有在一定的刺激条件下才能在体外和体内显示其增殖潜能。因此，应评估条件肝细胞和干细胞，因为它们显示出更大的再生潜力。目前对移植肝前体细胞的体内生长和分化潜能知之甚少。本课题的目的一方面是通过调节培养基的特异性诱导，在体外刺激肝细胞增殖，并研究生长中的肝细胞群的后向分化特征。另一方面，肝脏的前体细胞通过化学毒素的应用在体内被激活，随后从受体肝脏中分离出来。这两种细胞实体将被移植到DPPIV(-)- f334大鼠模型中。生长行为、分化和通过表面粘附分子与内源性细胞的相互作用将被用作追踪它们命运的手段。核心问题是前体细胞是否以及在多大程度上显示出更大的再生潜力，以及哪种策略可能导致未来以优化肝细胞移植为目的的受控细胞或组织替代。

Initial clinical results indicate that liver cell transplantation is a suitable method for the treatment of serious chronic liver disease. The mechanisms by which donor liver cells are integrated into the parenchyma and the recipient organ is repopulated are widely unclear. Adult hepatocytes display their proliferative potential in vitro and in vivo only under certain stimulation conditions. Therefore conditioned hepatocytes and stem cells should be evaluated, as they show a greater potential for regeneration. Very little is known at present about the in vivo growth and differentiation potential of transplanted hepatic precursor cells. The aim of the project proposed here is on the one hand to stimulate hepatocytes into proliferation in vitro through the specific induction with conditioning media and to examine the retrodifferentiation characteristics of the growing liver cell population. On the other hand, precursor cells of the liver are to be activated in vivo through the application of chemotoxins and subsequently isolated from the recipient liver. Both cell entities will be transplanted into the DPPIV(-)-F334 rat model. Growth behaviour, differentiation and interaction with endogenous cells via surface adhesion molecules will be utilised as a means to track their fate. The central question is whether and to what extent precursor cells display a greater regeneration potential and which strategies may result in the future for controlled cell or tissue replacement with the intention of optimising liver cell transplantation.