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• W2740955478 abstract "Introduction: Initial clinical results indicate that liver cell transplantation is a suitable method for the treatment of serious liver disease. Donor organ shortage markedly restricts the availability of adult hepatocytes as the primary source of cells. However, cells with precursor characteristics prove to be a promising alternative for transplantation applications. The aim is to investigate the adoption of precursor characteristics by hepatocytes proliferating in vitro (colony cells) as well as the qualitative comparison with hepatic stem cells generated in vivo (oval cells). Furthermore, the fate of both cell entities is tracked after transplantation into a rat liver regeneration model. Methods: Adult hepatocytes are stimulated into proliferation (forming ‘colonies’) in a culture system based on hepatocyte and non-parenchymal cell conditioned media supplemented with growth hormones as epidermal and fibroblast growth factors. Cell differentiation markers are assessed on the protein (immunohistochemistry) as well as the mRNA level (RT-PCR). In order to activate the intrahepatic stem cell niche in rat liver, carcinogenic stimulus (2-acetylaminofluorene) has to be combined with substantial hepatocellular cell loss (70 % partial hepatectomy). The phenotypic characteristics of the induced ‘oval cells’ are determined using immunofluorescence and FACS-analysis. To isolate oval cells, stimulated rat liver is perfused using a two step digestion method. The obtained cell suspension is further purified by Nycodenz ® gradient centrifugation. Transplantation and repopulation studies are performed in the DPPIV (Dipeptidylpeptidase IV) -mutant rat liver regeneration model (pre-treatment with retrorsine and partial hepatectomy). Results: Comparison in terms of both morphology and phenotype reveals a close relationship between oval cells generated in vivo and hepatocytes stimulated in vitro. Both cell types display the classic features of intrahepatic stem cells: They express the foetal markers alpha-fetoprotein and CD49f in addition to the bile duct marker Cytokeratin 7. Four months after the transplantation of colony cells, large clusters of differentiated hepatocytes derived from donors are visible within the host parenchyma. The distinct expression pattern of the antigens DPPIV, cytokeratin 18 and connexin 32 indicates the full integration and differentiation of donor cells. Three weeks after transplantation of an oval cell suspension, single donor cells can be detected within the recipient liver. Only some donor cells display the markers of mature hepatocytes, whereas most cells resemble endothelial cells. Conclusion: Oval cells and colony cells display features typical of stem cells committed to the liver. After transplantation into the rat liver regeneration model, colony cells repopulate the host parenchyma, whereas oval cells differentiate into mature hepatocytes only occasionally. However, both cells entities serve as a promising source for cell therapy of the diseased liver." @default.
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• W2740955478 date "2005-01-01" @default.
• W2740955478 modified "2023-09-24" @default.
• W2740955478 title "Leberrepopulation nach Transplantation von hepatischen Stammzellen Liver repopulation following transplantation of hepatic progenitor cells" @default.
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