DIABETER project is coordinated by Nadir Askenasy, MD, PhD, Frankel Laboratory, Centre for Stem Cell Research, Schneider Children’s Medical Centre of Israel
Type 1 diabetes (T1D) is an inflammatory reaction against pancreatic islets triggered by extrinsic precipitating factors in subjects with particular genetic configurations favorable to autoimmunity. Despite intensive interest in etiology, pathogenesis and mechanisms of this inflammatory reaction, reliable curative therapies are yet to be developed. Therefore, the scientific objective of DIABETER project is to design, refine and consolidate a clinically relevant cell therapeutic approach to cure diabetic autoimmunity by targeted delivery of apoptotic signals using mesenchymal stromal cells (MSC) as vehicles.
Previous studies of our and other groups have documented the need to deplete pathogenic cells in order to restore self-tolerance and the detrimental consequences of systemic immunosuppressive therapy, which causes disease recurrence during rebound recovery from lymphopenia. Targeted delivery of regulatory T cells (Treg) carrying death ligands to the site of inflammation has been proved a useful intervention in mouse model of T1D, but the effects were transient.
In this project, we extend our previous work by including MSC with the aim to produce sustained effects. MSC are endowed with intrinsic capacity to reduce inflammation and their killing capacity will be induced by transient expression of TNF death ligands. Furthermore, substitution of immune cells with autologous MSC is expected to improve islet recovery through support of stromal remodeling, vascularization, provision of cytokines and differentiation to produce insulin.
Besides its scientific goal, the ambition, aspiration and the strategic objective of DIABETER project is to further develop our infrastructure and increase the long-standing involvement of ICBP team in the research areas of diabetic and cardiovascular pathophysiology. By attracting a high level and recognized expert from abroad, the full capacity of the staff will be exploited and guided to pursue therapeutic approaches for autoimmune disorders and their complications.
It is envisioned that the successful conclusion of the project will: (i) improve our competitiveness at the European level; (ii) expand the activities and skills in cellular immunotherapies based on the existing excellent human and technical resources; (iii) provide a new generation of young investigators the opportunity to develop a scientific career under optimal conditions (4 new PhD students hired in the project); (iv) re-confirm the value of ICBP as “Centre of Excellence of the European Community”, gained by competition in 2000; (iv) foster collaborations with EU Centers, under Horizon 2020 program, and private entities towards development of commercial applications of this new immunotherapeutic strategy.