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Development of culture conditions for the differentiation of hES cells into hepatocytes

Objective

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.

Field of science

  • /natural sciences/biological sciences/cell biology
  • /medical and health sciences/medical biotechnology/cells technologies/stem cells

Call for proposal

FP7-HEALTH-2007-B
See other projects for this call

Funding Scheme

CP-FP - Small or medium-scale focused research project

Coordinator

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Address
Rue De Tolbiac 101
75654 Paris
France
Activity type
Research Organisations
EU contribution
€ 941 794
Administrative Contact
Audrey Laurent (Ms.)

Participants (6)

THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE
United Kingdom
EU contribution
€ 357 636
Address
Trinity Lane The Old Schools
CB2 1TN Cambridge
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Dawn Edwards (Ms.)
HADASSAH MEDICAL ORGANIZATION
Israel
EU contribution
€ 325 920
Address
N/a
91120 Jerusalem
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Aharon Tzukert (Dr.)
FUNDACION DE LA COMUNIDAD VALENCIANA CENTRO DE INVESTIGACION PRINCIPEFELIPE
Spain
EU contribution
€ 280 800
Address
Calle Eduardo Primo Yufera 3
46012 Valencia
Activity type
Research Organisations
Administrative Contact
Henar Armas (Ms.)
FLASH THERAPEUTICS
France
EU contribution
€ 307 339
Address
Canal Biotech Ii - 3 Rue Des Satellites
31400 Toulouse
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Pascale Bouillé (Dr.)
HELSINGIN YLIOPISTO
Finland
EU contribution
€ 551 400
Address
Yliopistonkatu 3
00014 Helsingin Yliopisto
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Tiina Berg (Ms.)
INSERM TRANSFERT SA
France
EU contribution
€ 234 990
Address
Rue Watt 7
75013 Paris
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Louis Jammayrac (Mr.)