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

分析条件成年肝细胞与肝前体细胞的生长和分化潜力，作为大鼠模型中肝脏再生的有效手段

• 批准号: 5378259
• 负责人: Professorin Dr. Sarah König
• 金额: --
• 依托单位: Klinik für Allgemein-, Viszeral- und Kinderchirurgie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2002
• 资助国家: 德国
• 起止时间: 2001-12-31 至 2004-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5378259?language=en
• 关键词: Analysis; growth; differentiation; potential; conditioned

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.

初步临床结果表明，肝细胞移植是治疗严重慢性肝病的合适方法。供体肝细胞整合到实质中并重新填充受体器官的机制尚不清楚。成年肝细胞在体外和体内仅在某些刺激条件下显示其增殖潜力。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。目前对移植的肝前体细胞在体内的生长和分化潜能知之甚少。本课题的目的是一方面通过条件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体的逆分化特性。另一方面，肝脏的前体细胞将通过应用化学毒素在体内活化，随后从受体肝脏分离。将两种细胞实体移植到DPPIV ㈠-F334大鼠模型中。将利用生长行为、分化和通过表面粘附分子与内源性细胞的相互作用作为追踪其命运的手段。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，以及未来可能导致哪些策略用于控制细胞或组织替代，以优化肝细胞移植。