Associated organisationsKing's College London · University of OxfordEurope PMC affiliations are not treated as award recipients or mapped locations.
Funding£2.9M
PeriodMar 2024 — May 2028
In plain English
AI plain-English summary
Transplanted stem-cell therapies for Type 1 diabetes die off within days, before blood vessels can grow to supply them. Researchers are building a synthetic scaffold that mimics the natural environment around pancreatic islets, combined with temporary genetic tweaks, to keep those cells alive long enough to function. The problem is stark: stem-cell-derived islet cells lose both number and function almost immediately after transplantation, before the graft develops its own blood supply. No one has yet solved how to stop this early cell death. This consortium targets two fronts simultaneously—the physical surroundings (extrinsic factors) and the cells’ internal survival machinery (intrinsic factors). They will engineer a biomaterial platform that recreates the cell-to-cell and cell-to-matrix signals islets normally receive, and use RNA-based molecules to transiently boost pro-survival gene expression without altering the genome. If successful, the work could transform stem-cell therapy from a promising concept into a reliable treatment that restores insulin production in people with Type 1 diabetes. The self-oxygenating modular device they plan for in vivo testing hints at a practical delivery system. This is fundamental science with a clear translational goal: keeping transplanted cells alive so patients can stop managing their blood sugar minute by minute.
View original technical description
The use of human pluripotent stem cell (SC)-derived islets holds promise as a therapy for Type 1 diabetes (T1D), but the lack of suitable conditions sustaining cell survival after transplantation represents an obstacle to its clinical application. The loss in number and functionality of SC-derived islet cells occurs shortly after transplantation, preceding adequate graft neovascularization. Hence, there is a critical knowledge gap concerning the fate of SC-islet cells upon engraftment and the main challenge remains to hamper such dramatic cell loss after transplantation. Our research proposal establishes a multi-disciplinary consortium with the ambitious goal of developing an innovative approach for sustaining cell longevity and functionality of SC-islet transplants. Specifically, we will target extrinsic and intrinsic prosurvival factors. To modulate the extrinsic factors, we will develop an innovative biomaterial platform to closely mimic the in vivo islet microenvironment, including cell-ECM and cell-cell communication, and enhance SC-islets survival. To engineer a prosurvival cell state, we will use new ways to transiently modify gene expression using non-integrating, RNA-based molecules in SC-islets. This will enable combinatorial screening of candidate mRNAs and siRNAs to identify optimal therapeutic approaches improving SC-islet survival and establishing ‘immune-protected niches’. The optimal strategies will be then assessed for their functionality in vivo using a self-oxygenating modular device. We expect that the knowledge and paradigms generated by our research programme will not only yield novel insights into islet cells survival but will also accelerate SC-therapy as a treatment that could significantly enhance the life quality of T1D patients.
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