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Beta Cell therapie in diabetes (EU345)

Type 1 diabetes is caused by a major loss in insulin-producing beta cells, which proceeds after diagnosis, often to complete depletion. The objective of our consortium is to develop and implement interventions for restoring the beta cell mass. Methods can differ with the stage of the disease but will require the same insights and address similar targets. In this FP7 program we investigated three tracks that can lead to beta cell replacement in patients. The first aims large-scale production of human beta (progenitor) cells that can generate metabolically adequate beta cell implants. The second searches for cells and/or compounds that activate beta cell progenitors and/or beta cell proliferation with the purpose of inducing beta cell regeneration in the pancreas. The third track seeks to design antibody-based therapies that induce immune tolerance to regenerated beta cells or to a beta cell implant. Our five-year plan addressed the following specific objectives:

1. Generate human beta (progenitor) cells through programming of human embryonic stem cells or through reprogramming of human differentiated cells, and assess their therapeutic potential in preclinical models.
2. Activate beta cell formation in the pancreas and assess their therapeutic potential in preclinical models.
3. Develop generic tolerance-inducing protocols in animal models of autoimmunity and transplantation.
4. Define markers for monitoring functional beta cell mass and immune state in beta cell therapy protocols.
5. Translate findings to novel clinical protocols to restore functional beta cell mass in type 1 diabetes patients.

Work undertaken towards these objectives has provided tools and insights that should guide novel clinic trials in beta cell transplantation, in beta cell preservation and regeneration, as well as direct further laboratory research to overcome identified obstacles. These trials are aiming for a considerably better outcome and wider application than with current interventions, as have been undertaken
- shortly after clinical onset of the disease, consisting of transient suppression of autoimmune activity
- at a late stage of clinical disease, consisting of intraportal transplantation of human beta cell preprations isolated from donor organs

Consortium structure
The consortium addresses its overall objective through collaborative activities at and between three levels, ie an R&D platform, preclinical models and clinical trials. Its central unit manages and coordinates the program according to the roadmap, its milestones and its funding. For this FP7-supported program the tasks at the three levels are listed in Fig (see attachement) with indication of the associated WP-numbers.
Datum:1 jan 2010  →  30 jun 2015
Trefwoorden:Cell Therapy, Prevention, Transplantation, Diagnostic Tests, Immunology, Cell Death and Survival, Islet Cell Pathology, Islet Cell Biology, Beta Cell Transplantation, Diabetes