Starting date : Jun 2015 > Dec 2019
Lifetime:52 months
Program in support : NMP-10-2014 Biomaterials for the treatment of diabetes mellitus
Status of project : complete
CEA-Leti's contact :
Project Coordinator: CEA-Leti
Partners: - BE: Université catholique de Louvain (UCL)
- DE: Charité-Universitätsmedizin Berlin (CUB),
- European Research Services GmbH (ERS)
- ES: Nanoimmunotech (NIT)
- FR: CEA-Leti,
- Etablissement Français du Sang (EFS),
- Universtié Grenoble Alpes (UGA)
- NO: NovaMatrix/FMC BioPolymer (NOVA)
- USA: Wake Forest University Health Sciences (WFUHS)
Target market: n/a
Investment: € 8 mi
EC Contribution: € 8 mi
Releases
Oral presentations: «Innovative microfluidic-based technics for advance therapy medicinal product for the treatment of type-1 diabetes», F. Bottausci, M. Pierron, D. Rabaud, N. Sarrut, J.-L. Pesce, C.-E. Goujon, M. Alessio, F. Boizot, C. Fontelaye, E.Tubbs, C. Laporte, S .Lablanche, P.-Y.Benhamou, M. Orhant-Prioux, A. Moisan, F. Rivera, BioEngineering 2019 Summit - San Diego, USA - 1-2 April 2019.
«Innovative microfluidic-based technics for advance therapy medicinal product for the treatment of type-1 diabetes», M. Pierron, F. Bottausci, D. Rabaud, N. Sarrut, J.-L. Pesce, C.-E. Goujon, M. Alessio, F. Boizot, C. Fontelaye, E. Tubbs, C. Laporte, S. Lablanche, P-Y.Benhamou, M. Orhant-Prioux, A. Moisan, F. Rivera, IEEE NEMS 2019 - Bangkok, hailand - 11-14 April 2019.
Number of patents: n/a
| Stakes
- The strategy adopted for protecting pancreatic islets from immune rejection is to microencapsulate them in soft, porous, biocompatible microcapsules. CEA-Leti was project coordinator and leader for microcapsule production, characterisation, dissemination and planned usage.
Demonstration of the positive role of mesenchymal stem cells (MSCs) and tripeptides arginine- glycine-aspartic acid conjugated to sodium alginate (RGD-alginate) on rat islet viability and functionality through co-culture experiments
Optimised production of GMP ultra pure Extra Cellular Matrix (ECM) mimicking the pancreatic islet microenvironment. Tests in vitro shown close biocompatibility and improvement in islet viability and functionality
Development of a zwitterionic (ZW) chitosan for coating microcapsules and preventing fibrosis. ZW chitosan was shown to be biocompatible without affecting capsule porosity. Initial in vivo assays proved that ZW coating reduced macrophages in the capsule periphery.
- These results enabled final bioactive capsule composition to be defined and patented. The encapsulation challenge was to produce monodispersed microcapsules in the extremely high viscous fluid (10Pa.s) required by the microcapsule composition, while minimising the impact on cell viability. This was overcome by:
- Designing, manufacturing and testing an innovative, cheap, disposable, microfluidic plastic cartridge to produce the microcapsules automatically.
- Designing and manufacturing new versatile GMP similar equipment. This automatically produces sterile capsules by simply plugging in the microfluidic cartridge and operating the patented instrument. Capsules with allogenic islets were implanted into diabetic rats and shown good immunocompatibility and stability after several weeks.
- Glycaemic control is the key therapeutic issue in diabetes mellitus types I and II. Quality of life would benefit enormously from curtailment of constant self-control by insulin injection and long-term complications. The best therapeutic option is transplantation of allogeneic islet cells (from a human donor) but the current state of the art limits this approach's applicability.
- Implanting unprotected grafts demands lifelong administration of immunosuppressants. Moreover, cell protection against adverse immune reactions by today's encapsulation strategies so reduces graft functionality and survival that frequent 'refresher' implants are necessary. The encapsulated approach currently offers a maximum of two years glycaemia control.
- The purpose of the BIOCAPAN project, which brought together experts from different fields, was to develop an innovative treatment based on implanting allogeneic islet cells embedded in a complex microcapsule. The objective was to design a GMP grade bioactive microcapsule that maximizes long-term functionality and survival of pancreatic islets by preventing pericapsular fibrotic overgrowth, in-situ oxygenation, innovative extracellular matrix microenvironment reconstruction and immune system modulation. CEA Leti's mission was to establish a GMP grade microfluidic microencapsulation platform to protect freshly harvested islets quickly in a standardized, reproducible manner. The ambition was to design a microfluidic disposable cartridge the size of a credit card; this would be inserted into the equipment to produce microencapsulated islets automatically.
- The project aimed for the full preclinical validation and a comprehensive protocol, complying with the provisions of Advanced Therapy Medicinal Products Regulation in order to start clinical trials within one year of project completion. The target was 5 years of insulin injection free treatment without immunosuppressants; this would be of enormous benefit to diabetes mellitus patients dependent on insulin (all Type I and approximately 1/6 Type II patients).
- Microencapsulation of islets in a viscous biopolymer is a world-class result. The project enabled definition and patenting of the microcapsule composition and the encapsulating instrument. The intention of the patenting strategy is to attract potential industrial partners for further commercialisation. The project built a strong relationship between its partners. Spin-offs in cell therapy product development are emerging from this collaboration and from the results of the BIOCAPAN project.
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