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

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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.