CAPITAL

Diabetes is a major public health problem in the world. In 2018, this pathology is still responsible of severe complications (end-stage renal failure, dialysis, blindness). The treatment for type 1 diabetic (T1D) patients and for approximately 15% of insulin-treated type 2 diabetic patients relies partly on: the daily administration of insulin, the multi-daily control of their blood glucose, their dietary carbohydrates, and the daily adjustment of their insulin therapy. However, the treatment for diabetes remains insufficient to restore optimal metabolic control, and patients continue to develop complications linked to their diabetes. In addition, some T1D patients develop a particular form of diabetes, unstable diabetes that exposes them to: major changes in their blood glucose levels and the occurrence of severe metabolic events. The future of the treatment of diabetes, especially type 1, is turned towards cell therapy or islet transplantation of Langerhans, which proposes to transplant to the T1D patient suffering from unstable diabetes of the islets of Langerhans, functional anatomical units containing insulin secreting cells. This technique has been shown to be efficient in restoring optimal glycemic control in humans with currently over 1000 islet transplanted patients. Insulin weaning can be achieved in half the patients after 1 year. Islet transplantation remains limited to a limited number of patients because of the sometimes severe risks of immunosuppressive therapy, which remains essential. There is also a loss of long-term graft functionality and a shortage of islet graft that limits the applicability of the technique to a larger number of patients. The future of the islet transplantation technique will have to be without immunosuppressive therapy, finding an alternative source to human islets, and enabling more sustainable graft functionality. The BIOCAPAN (BIOactive implantable CApsule for PANcreatic islets immunosuppression free therapy) consortium has been developing since 2015 a translational research project funded by European H2020. This project aims at the industrial development on a large scale, of microcapsules consisting of islets encapsulated by a microfluidic technique in the presence of different biopolymers offering the prospect of being able to graft these islets without any immunosuppressors while also increasing their functionality. The current BIOCAPAN project is, to our knowledge, the first project allowing the GMP and industrial production of encapsulated islets and combining all the biomaterials composing the biocapsule. During the BIOCAPAN project, the availability of human islets, the heart of the capsule composition, has emerged as a major limiting factor, leading to having recourse to an alternative source to the islets. The CAPITAL project is based on the innovations developed during the BIOCAPAN project and proposes to associate an alternative source of cells to the human islets by proposing the use of insulin-secreting cells obtained from induced pluripotent stem cells, the use of islets genetically modified pork or the use of biopolymers capable of releasing insulin. Thus, the translational research project CAPITAL, consisting of scientists, industrials and clinical research team expert in T1D cell therapy and aiming at the development and transplantation of insulin-secreting biocapsules in diabetic patients (80 million worldwide) is fully in line with the call for projects H2020 sc1-bhc-07-2019.