The first six months will provide time to up-scale the capacities of all participating groups. The up-scaling is a crucial component of the Chicago Project and will allow for application of large-scale screening methods.
Year 1 Joint Research Projects
Accelerate understanding of normal development of insulin-producing cells in mouse models
Screen for genes and conditions allowing for generating insulin-producing human cells
Screen for factors deleterious to islets
Screen and select the most appropriate raw materials for encapsulation
The second year will provide the first islet-cell lines by integrating the knowledge of the developmental and molecular biologists into subprojects working on different cell types within the adult human pancreas. The encapsulation technology must be up-scaled for use in large-animal models and later in clinical trials. Appropriate large-animal models must be established to extensively test encapsulated-islet transplantation before clinical use.
In the third year, project members will test extensively the established cell lines to ensure appropriate function and safety. The best transplant site will be determined for animal models. As well, the conditions and tools for generating insulin cells will be optimized and up-scaled to prepare for preclinical experiments in larger animals.
Year four focuses on delivering a reproducible, encapsulated, functional islet-cell graft for testing in clinically relevant large-animal models. By the end of the fourth year, project members expect to identify the optimal cell sources and to establish an unlimited source of insulin-cells for clinical testing. Project members also expect to have identified strategies to prevent destruction of the insulin cells in diabetic patients.
The team must meet good laboratory and manufacturing practice conditions (regulatory standards for medical products) for the production of the insulin cells and the encapsulation process. The safety of the graft will be documented in year four before clinical Phase I safety trials can be initiated in patients.
In year five of the Chicago Project, Phase I clinical trials with encapsulated islet-cell line transplants will begin in diabetic patients. The first Phase I trial will investigate how the encapsulated insulin-cells survive in a diabetic patient by implanting it under the skin and retrieving it after various periods of time.
The second Phase I trial will aim at treating diabetic patients with a sufficient amount of encapsulated insulin-cells rendering the patient independent of insulin injections corresponding to a functional cure of diabetes.
The proof of concept will allow for further development beyond the Chicago Project and allow for widespread clinical application of a cell-based therapy for diabetes.
Encapsulated islet-cell graft:
The cells are generated in culture systems in the laboratory and protected by as electively permeable capsule. The insulin producing cells will allow for controlling blood glucose levels in a physiological manner. The capsule will protect against the assaults of immune cells and antibodies, but allow nutrients and insulin to pass.