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Upscaling human insulin-producing beta cell production by efficient differentiation and expansion of endoderm progenitors

Objective

Despite progress in producing beta cells from human pluripotent stem cells (hPSCs) in recent years, full differentiation cannot be obtained in vitro. The HumEn project hypothesises that a fundamental understanding of the coupling between endodermal progenitor expansion and differentiation is relevant for elucidating how to a) generate glucose-responsive beta cells from hPSCs in vitro, and b) generate sufficient number of beta cells to meet future clinical needs in cell therapy in diabetes. Thus, the overall aim of HumEn is to identify, understand, and expand human endodermal progenitors as a consistent and renewable source of cells for pancreatic beta cells differentiation.
We will focus on precursors from two stages of pancreatic differentiation; anterior definitive endoderm (ADE) and pancreatic endoderm (PE) progenitors, providing mechanistic insight into the signalling pathways and downstream targets that control their expansion and functional maturation into human beta cells. Rigorous in vitro (regulated insulin-release) and in vivo (protection against experimentally induced diabetes in mice) testing of insulin-producing cells will ensure a functional end product. The consortium proposes to address these problems by a unique combination of models and experimental approaches, including genetic, surface/biomaterial screens (3D), and cell surface antibody screens as well as cell signalling-to-transcription factor/chromatin effectors. In the end, HumEn aims to deliver a reliable and scalable protocol for directed differentiation of hPSCs into bona fide beta cells. The results of the project will not only provide answers to fundamental questions, but also deliver new concepts and knowledge of general importance for coordination of cell cycle progression and regulation of cell fate specification in stem cells/progenitors.
HumEn is highly innovative and carries excellent potential for translational output.

Field of science

  • /medical and health sciences/clinical medicine/endocrinology/diabetes
  • /medical and health sciences/medical biotechnology/cells technologies/stem cells

Call for proposal

FP7-HEALTH-2013-INNOVATION-1
See other projects for this call

Funding Scheme

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

Coordinator

KOBENHAVNS UNIVERSITET
Address
Norregade 10
1165 Kobenhavn
Denmark
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 935 725
Administrative Contact
Bjarne Friis Ploumark (Mr.)

Participants (8)

HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH
Germany
EU contribution
€ 485 927
Address
Ingolstadter Landstrasse 1
85764 Neuherberg
Activity type
Research Organisations
Administrative Contact
Jürgen Ertel (Dr.)
THE UNIVERSITY OF EDINBURGH
United Kingdom
EU contribution
€ 914 892
Address
Old College, South Bridge
EH8 9YL Edinburgh
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Angela Noble (Ms.)
INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
France
EU contribution
€ 441 020
Address
Rue De Tolbiac 101
75654 Paris
Activity type
Research Organisations
Administrative Contact
Téva West (Mr.)
UPPSALA UNIVERSITET
Sweden
EU contribution
€ 503 369
Address
Von Kraemers Alle 4
751 05 Uppsala
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Birgitta Gustavsson (Mrs.)
MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Germany
EU contribution
€ 514 700
Address
Hofgartenstrasse 8
80539 Muenchen
Activity type
Research Organisations
Administrative Contact
Susanne Schneider (Dr.)
CYTOO SA
France
EU contribution
€ 423 560
Address
Parvis Louis Neel 7 Bht Batiment 52
38000 Grenoble
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Laurence Fayand (Mrs.)
MATERIOMICS BV
Netherlands
EU contribution
€ 537 965
Address
Oxfordlaan 70
6229 EV Maastricht
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Frank-Jan Van Der Velden (Mr.)
MILTENYI BIOTEC GMBH
Germany
EU contribution
€ 205 486
Address
Friedrich Ebert Strasse 68
51429 Bergish Gladbach
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Miriam Haak (Dr.)