Krause, Petra

[["dc.bibliographiccitation.firstpage","805"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Cell Transplantation"],["dc.bibliographiccitation.lastpage","817"],["dc.bibliographiccitation.volume","23"],["dc.contributor.author","Krause, Petra"],["dc.contributor.author","Unthan-Fechner, Kirsten"],["dc.contributor.author","Probst, Irmelin"],["dc.contributor.author","Koenig, Sarah"],["dc.date.accessioned","2018-11-07T09:46:06Z"],["dc.date.available","2018-11-07T09:46:06Z"],["dc.date.issued","2014"],["dc.description.abstract","Clinical studies have proved the therapeutic potential of hepatocyte transplantation as a promising alternative to whole organ liver transplantation in the treatment of hereditary or end-stage liver disease. However, donor shortage seriously restricts cell availability, and the lack of appropriate cell culture protocols for the storage and maintenance of donor cells constitutes a significant obstacle. The aim of this study was to stimulate mature hepatocytes in culture to multiply in vitro and track their fate on transplantation. Rat hepatocytes isolated nonenzymatically were cultured serum free for up to 10 days. They were stimulated into proliferation in the presence of growth factors and conditioned media from nonparenchymal and hepatocyte culture supernatants, as well as 10 mM lithium chloride (LiCl). Cell proliferation was assessed by determining DNA content. Additionally, the extent of cell differentiation was estimated using immunofluorescence staining of hepatic, biliary, progenitor, and mesenchymal markers and gene expression analyses. Transplantation studies were performed on the Fischer CD26-mutant rat following pretreatment with retrorsine and partial hepatectomy. Proliferating hepatocytes increasingly adopted precursor characteristics, expressing progenitor (OV6, CD133), hepatic lineage (CK18), biliary (CD49f, CK7, CK19), and mesenchymal (vimentin) markers. The supplement of LiCl further enhanced the proliferative capacity by 30%. Transplantation studies revealed extensive repopulation by large donor hepatocyte clusters. Furthermore, bile duct-like structures deriving from donor cells proved to be immunoreactive to ductular markers and formed in close proximity to endogenous bile ducts. Mature hepatocytes reveal their potential to \"switch\" between phenotypes, adopting progenitor characteristics during proliferation in vitro. Following transplantation, these \"retrodifferentiated\" cells further expanded in vivo, thereby generating bipotentially differentiated progenies (hepatocytes and bile duct-like structures). This apparent plasticity of mature hepatocytes may open new approaches for cell-based strategies to treat liver disease."],["dc.identifier.doi","10.3727/096368913X664856"],["dc.identifier.isi","000337989700002"],["dc.identifier.pmid","23485196"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10644"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/34784"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Cognizant Communication Corp"],["dc.relation.issn","1555-3892"],["dc.relation.issn","0963-6897"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Cultured Hepatocytes Adopt Progenitor Characteristics and Display Bipotent Capacity to Repopulate the Liver"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","205"],["dc.bibliographiccitation.issue","5-6"],["dc.bibliographiccitation.journal","In Vitro Cellular & Developmental Biology - Animal"],["dc.bibliographiccitation.lastpage","212"],["dc.bibliographiccitation.volume","45"],["dc.contributor.author","Krause, Petra"],["dc.contributor.author","Saghatolislam, Farahnaz"],["dc.contributor.author","Koenig, Sarah"],["dc.contributor.author","Unthan-Fechner, Kirsten"],["dc.contributor.author","Probst, Irmelin"],["dc.date.accessioned","2018-11-07T08:30:19Z"],["dc.date.available","2018-11-07T08:30:19Z"],["dc.date.issued","2009"],["dc.description.abstract","Primary hepatocytes lose their differentiated functions rapidly when in culture. Our aim was to maintain the differentiated status of hepatocytes in vitro by means of vital hepatic stellate cells (HSCs), their soluble and particulate factors and lipid extracts. Hepatocytes were placed into collagen-coated culture dishes in the presence of HSCs at different ages of pre-culture, with or without direct cell to cell contacts, at different cell ratios and in monoculture with cellular HSC components in place of vital cells. Changes in morphology and enhancement of phosphoenolpyruvate carboxykinase (PCK) activity by glucagon were used to determine the differentiated status of hepatocytes in 2d-short-term culture. HSCs proved able to maintain the differentiated function of hepatocytes in co-culture either by direct cell contacts or via factors derived from HSC-conditioned medium. In comparison, however, without cellular contact to hepatocytes five to ten times as many HSCs were necessary to increase the PCK activity to the same degree as in the presence of intercellular contacts. Whereas stimulation in the presence of HSC/hepatocyte contacts was independent of HSC culture age only quiescent, resting HSCs (precultured for 1-2 d) were able to stimulate hepatocytes significantly via soluble factors. Culturing of hepatocytes with a lipid extract or a particulate fraction from HSCs clearly displayed a very strong beneficial effect on enzyme activity and morphology. HSCs maintain hepatocyte function and structure through preferentially cell-bound signalling and transfer of lipids."],["dc.identifier.doi","10.1007/s11626-008-9166-1"],["dc.identifier.isi","000266261700002"],["dc.identifier.pmid","19184253"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?goescholar/3608"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/16865"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","1071-2690"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Maintaining hepatocyte differentiation in vitro through co-culture with hepatic stellate cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]