Obiettivo The liver is associated with many types of diseases which can only be treated by Orthotopic liver transplants. However, shortage of organ donors represents a major limitation for wide-application of this therapy. Additionally, expansion of fully-functional hepatocytes in vitro remains an important challenge for the drug discovery industry. Human Embryonic Stem cells (hESCs) offer a promising new solution to these problems. hESCs are able to grow indefinitely in vitro while maintaining their capacity to differentiate to all types of cells. Here we propose to develop standardized, animal-free culture conditions to promote the differentiation and expansion of fully-functional hepatocytes from hESCs using four complementary Workpackages (WPs): Development of novel tools: WP1 will develop 3-D growth matrices, lentivirus-based reporter systems, liver-specific endothelial cells and a miRNA platform to facilitate the sequential process of establishing standardized, animal-free conditions to produce ES-derived hepatocytes. Generation of Anterior Definitive Endoderm multipotent stem cells: WP2 will define culture conditions to drive differentiation of hESCs to ADE cells, the earliest progenitors of liver cells during mammalian development. Proof-of-principle of conditions will be validated using the various hESC lines available from partners. Differentiation and expansion of hepatic progenitors from multipotent ADE cells using defined conditions: WP3 will be devoted to the generation of hepatic progenitors from ADE cells. Function will be validated in vitro and in vivo using human foetal hepatic progenitors and HepaRG human hepatoma cells as positive controls. Generation of mature hepatocytes from ES-derived hepatic progenitors: WP4 will generate functional hepatocyte lines suitable for drug testing and future preclinical evaluation. Results of the LIV-ES project will provide new insights into stem cell biology and establish a rationale basis for cell-based therapies. Campo scientifico medical and health sciencesbasic medicinepharmacology and pharmacydrug discoverynatural sciencesbiological sciencescell biologymedical and health sciencesmedical biotechnologycells technologiesstem cells Parole chiave Human embryonic stem cells animal-free defined animal-free defined culture conditions cell therapy hepatocyte differentiation liver diseases toxicology Programma(i) FP7-HEALTH - Specific Programme "Cooperation": Health Argomento(i) HEALTH-2007-1.4-7 - Development of stem cell culture conditions Invito a presentare proposte FP7-HEALTH-2007-B Vedi altri progetti per questo bando Meccanismo di finanziamento CP-FP - Small or medium-scale focused research project Coordinatore INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE Contributo UE € 941 794,00 Indirizzo RUE DE TOLBIAC 101 75654 Paris Francia Mostra sulla mappa Regione Ile-de-France Ile-de-France Paris Tipo di attività Research Organisations Contatto amministrativo Audrey Laurent (Ms.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato Partecipanti (6) Classifica in ordine alfabetico Classifica per Contributo UE Espandi tutto Riduci tutto THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE Regno Unito Contributo UE € 357 636,00 Indirizzo TRINITY LANE THE OLD SCHOOLS CB2 1TN Cambridge Mostra sulla mappa Regione East of England East Anglia Cambridgeshire CC Tipo di attività Higher or Secondary Education Establishments Contatto amministrativo Dawn Edwards (Ms.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato HADASSAH MEDICAL ORGANIZATION Israele Contributo UE € 325 920,00 Indirizzo N/A 91120 Jerusalem Mostra sulla mappa Tipo di attività Higher or Secondary Education Establishments Contatto amministrativo Aharon Tzukert (Dr.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato FUNDACION DE LA COMUNIDAD VALENCIANA CENTRO DE INVESTIGACION PRINCIPEFELIPE Spagna Contributo UE € 280 800,00 Indirizzo CALLE EDUARDO PRIMO YUFERA 3 46012 Valencia Mostra sulla mappa Regione Este Comunitat Valenciana Valencia/València Tipo di attività Research Organisations Contatto amministrativo Henar Armas (Ms.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato FLASH THERAPEUTICS Francia Contributo UE € 307 339,00 Indirizzo 3 AVENUE HUBERT CURIEN 31100 Toulouse Mostra sulla mappa Regione Occitanie Midi-Pyrénées Haute-Garonne Tipo di attività Private for-profit entities (excluding Higher or Secondary Education Establishments) Contatto amministrativo Pascale Bouillé (Dr.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato HELSINGIN YLIOPISTO Finlandia Contributo UE € 551 400,00 Indirizzo YLIOPISTONKATU 3 00014 Helsingin Yliopisto Mostra sulla mappa Regione Manner-Suomi Helsinki-Uusimaa Helsinki-Uusimaa Tipo di attività Higher or Secondary Education Establishments Contatto amministrativo Tiina Berg (Ms.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato INSERM TRANSFERT SA Francia Contributo UE € 234 990,00 Indirizzo 10 RUE D'ORADOUR-SUR-GLANE - PARISANTE CAMPUS 75015 PARIS Mostra sulla mappa Regione Ile-de-France Ile-de-France Paris Tipo di attività Private for-profit entities (excluding Higher or Secondary Education Establishments) Contatto amministrativo Louis Jammayrac (Mr.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato