Cel Embryonic stem cells (ESC) have a limitless capacity for self-renewal a remarkable ability to differentiate, promising a limitless source of cells for cell therapies and tissue engineering. Organ scarcity and lack of proliferative ability makes ESC-derived hepatocytes one of the few potential sources of cells for clinical applications and pharmaceutical drug discovery. However, current techniques for hepatocyte differentiation result in mixed cell populations, minimal metabolic function, and long-term de-differentiation. These differences between mature and differentiated hepatocytes are due to insufficient development of the hepatic transcriptional network during differentiation. Preliminary evidence suggests that modifying the nutritional state of ESC-derived hepatocytes by lowering glucose and increasing fatty acids, mimicking suckling, results in a more mature hepatic phenotype, possibly through the induction of the fatty acid-responsive nuclear receptors, PPARa and HNF4a. This result is interesting as the role of nutrients in differentiation has yet to be elucidated in spite of well known nutritional changes during the pre- and post-natal periods. The hepatic nuclear receptor network is especially important in this context as these ligand-activated transcription factors respond to glucose, sterols, fatty and bile acids offering an epigenetic point of regulation in the development of liver metabolism. The technology which allows us to elucidate and control transcriptional events during differentiation is a microdevice termed the Living Cell Array (LCA). The LCA is a microfabricated device containing multiple GFP reporter cells under microfluidic control allowing high-throughput screening of changes in transcriptional activity during ESC differentiation. The ability of the LCA to monitor transcriptional activity dynamics in high-throughput makes it a unique tool for the study of hepatocyte differentiation under varying nutritional stimulation. Dziedzina nauki medical and health sciencesbasic medicinepharmacology and pharmacydrug discoverymedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsmedical and health sciencesmedical biotechnologytissue engineeringmedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesclinical medicineobstetricspostnatal care Program(-y) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Temat(-y) FP7-PEOPLE-2009-RG - Marie Curie Action: "Reintegration Grants" Zaproszenie do składania wniosków FP7-PEOPLE-2009-RG Zobacz inne projekty w ramach tego zaproszenia System finansowania MC-IRG - International Re-integration Grants (IRG) Koordynator THE HEBREW UNIVERSITY OF JERUSALEM Wkład UE € 100 000,00 Adres EDMOND J SAFRA CAMPUS GIVAT RAM 91904 Jerusalem Izrael Zobacz na mapie Rodzaj działalności Higher or Secondary Education Establishments Kontakt administracyjny Hani Ben Yehuda (Ms.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych
