MICROLIVERMATURATION
Gene network-based maturation of embryonic stem cell-derived hepatocytes in a microfabricated array
| Coordinatore | THE HEBREW UNIVERSITY OF JERUSALEM.
Organization address
address: GIVAT RAM CAMPUS contact info |
| Nazionalità Coordinatore | Israel [IL] |
| Totale costo | 100˙000 € |
| EC contributo | 100˙000 € |
| Programma | FP7-PEOPLE
Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) |
| Code Call | FP7-PEOPLE-2009-RG |
| Funding Scheme | MC-IRG |
| Anno di inizio | 2011 |
| Periodo (anno-mese-giorno) | 2011-03-01 - 2015-02-28 |
Partecipanti
| # | ||||
|---|---|---|---|---|
| 1 |
THE HEBREW UNIVERSITY OF JERUSALEM.
Organization address
address: GIVAT RAM CAMPUS contact info |
IL (JERUSALEM) | coordinator | 100˙000.00 |
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Obiettivo del progetto (Objective)
'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.'