BIOSID

A bioartificial pancreas to treat type 1 diabetes: optimization of cell survival and function in preclinical and clinical phases

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 Obiettivo del progetto (Objective)

'MAILPAN (MAcroencapsulation of PANcreatic Islets) is a prototype of bioartificial pancreas usable in the human designed to treat type 1 diabetic patients. The prototype was developed along different stages since 1996 and led to the creation of the SME called Defymed in 2011. Next step is now to bring the prototype to the pre-clinical and clinical phases necessary to the ensuing commercialization of MAILPAN whose ultimate goal is to improve the life of at least 20 million persons in the world while providing positive effects on healthcare management and expenses, the environment and the competitiveness of the biomaterials industry.

In order to reach this goal, CeeD and Defymed gathered a consortium made of seven partners from academia, clinical/public health research sector and industry/SMEs from three different European countries –Belgium, France and UK. The expertise gathered include encapsulation techniques, islet isolation, cell engineering, islet transplantation, islet preconditioning, surgical implantation, and medium formulation; items that are complementary and necessary to the implementation of the present project proposal.

The project proposal of a 36-month duration intends to bring the most modern and up to date improvements that the bioartificial pancreas still needs and can receive such as to enhance cells survival inside the device by formulating a new adapted cell culture medium, to further lower the rejection risk by studying the biocompatibility and anti-inflammatory mechanisms, to test the prototype in primates, and to validate its further use in humans. Safety, bio-compatibility and interoperability of MAILPAN device combined to the islets/pseudo-islets, will be assessed, in respect to the applied regulatory directives.'

Descrizione progetto (Article)

Diabetes management currently involves a modified diet and lifestyle as well as insulin therapy or pancreas/islets transplantation. Insulin therapy requires constant glucose monitoring, and issues with transplantation include use of immunosuppressive drugs, donor incompatibility, organ shortage and rejection.

Macroencapsulation of pancreatic islets (MAILPAN) is a prototype of a bioartificial pancreas device that uses encapsulation with artificial membranes to ensure effective immune isolation of insulin-secreting cells. Selective permeability in the membranes will obviate the need for immunosuppressive therapy.

The http://biosid-eu.org/ (BIOSID) project is optimising MAILPAN for pre-clinical and clinical testing. The goal is to facilitate rapid commercialisation of this technology after ensuring safety, biocompatibility and efficacy. For this purpose, they focused on minimising rejection of transplanted islets of Langerhans cells while maximising their function. They also worked on optimising properties of the MAILPAN membrane.

Within the first 18 months of the project period itself, BIOSID elucidated the physical-chemical conditions and mechanisms affecting islet survival and function. Major factors adversely affecting islet survival and function in MAILPAN were found to be islet cell confinement and hypoxia. Hypoxia is a condition where oxygen levels are inadequate.

Project findings paved the way for the development of a high-throughput platform to identify promising molecules and molecule combinations that can effectively counteract adverse conditions. The shortlisted molecules can then be utilised in cell culture medium to optimise cell viability and function in MAILPAN. EndoC-betaH1 are stable insulin-producing glucose-responsive cells that have successfully rescued mice with chemically induced diabetes. These cells were selected for transplantation in the device prototype.

Researchers also demonstrated the safety and biocompatibility of MAILPAN in small and large animal models. However, testing is ongoing using different cell types and cell origins for further optimisation. Such promising data should aid in obtaining approvals for human clinical trials.

Project activities were disseminated via the website, several international meetings, over 20 press media and 7 congresses.

Successful outcomes in tests on primate models will ensure faster authorisation of the optimised MAILPAN device for human clinical studies. Ultimately, faster commercialisation should improve the prognosis and quality of life for millions of diabetics.