Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.1.4-1 | Award Amount: 7.86M | Year: 2014
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.
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2011.1.1-1 | Award Amount: 5.90M | Year: 2011
The MEHTRICS proposal aims to challenge the current limits of HT cell-based screening by combining HT-RNAi with an emerging new technology for normalizing cultured cell behaviors, namely the growth of cells on adhesive micropatterns. Initial applications of this technology have already demonstrated its potential for enhancing the quality of existing high content analyses by radically reducing the cell populations phenotypic variability, resulting in much lower cell sampling requirements. This approach also promises to open up major new assay development space by broadening the range of analysis strategies that drive the novel cell-based assay designs, whose evolution has otherwise stagnated in recent years. The consortium will carry out several parallel and complementary lines of development to diversify the applicability of the MEHTRICS platform for both academic and industrial uses, ultimately validating the new capabilities through proof of principle screens. Our key objectives are 1) to optimize micropattern geometries and compositions to accommodate extended timelines typical of siRNA assays, 2) to integrate the promising Transfected Cell Array (TCA) technique to decrease cost and increase throughput, 3) to develop novel cell models of key diseases based on micropatterned adult stem cells and polarized epithelia/endothelial architectures and 4) to validate each of these implementations in key industry-relevant siRNA screening applications. Since experimental designs required to run RNAi screens are among the most demanding of all HT/HC studies and encompass virtually all technical challenges also encountered in compound screens, we expect the proposed scope of activities to deliver the maximal potential for impactful innovation, widespread adoption and clear relevance for all major applications of HT/HC cell screening. The resulting new tools and methodologies will be incorporated into the commercial offerings of the consortiums two key SMEs, CYTOO and CENIX.