DMIOL

Microencapsulation of Islets within Functionalized Peg Hydrogel

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 Obiettivo del progetto (Objective)

'Diabetes mellitus has a Europe prevalence of approximately 48 million people, including approximately 1 million with Type I diabetes. Despite the availability of exogenous insulin, life expectancy and quality are still diminished by chronic or late complications of the disease. These complications can be mitigated by restoring near-normal levels of glucose. The most effective strategy to do so relies on transplanting islets from donor tissue (in the form of a whole pancreas or isolated islets). Islet transplantation has evolved as a meaningful treatment option for Type I diabetes, but its widespread application has been limited by the need for immunosuppression and limited donor tissue supply. Theoretically, this membrane serves as a mechanical barrier isolating the graft from recipient leukocytes and antibodies while continuing to allow the diffusion of glucose, water, insulin, oxygen, nutrients, and cellular waste.. This research will focus on microencapsulation of islets with functional coats in order to address many of the shortcomings associated with current techniques of immunoisolation. In this project, the technique of interfacial photopolymerization will be employed to immunoisolate islets with functional PEG hydrogel coats. Encapsulation of islets using interfacial photopolymerization is necessary to achieve higher yields to test in vivo function and immunoprotection of islets encapsulated by this method. The hypothesis is that, by employing interfacial photopolymerization along with the techniques presented in this proposal it will be possible to microencapsulate rodent and canine islets in capsules of adequate quantity and consistent quality and that the function of islets microencapsulated by this method will be equivalent to that of unencapsulated islets in environments where allogeneic and xenogenic immunologic rejection are not factors, and superior in models in which rejection is a factor.'

Introduzione (Teaser)

Millions of Europeans suffer from diabetes along with other associated lifelong complications despite insulin administration. To find novel therapies, a European study proposed the transplantation of pancreatic islets in a hydrogel matrix.

Descrizione progetto (Article)

Type 1 diabetes is an autoimmune disease which presents with lack of insulin production due to the destruction of pancreatic beta islets. Given that insulin is required for the breakdown of sugars into glucose, an inability to produce energy has serious complications.

Islet transplantation is a promising alternative to insulin administration but is limited by the need for immunosuppression and lack of tissue. The EU-funded 'Microencapsulation of islets within functionalized peg hydrogel' (DMIOL) study proposed an approach for isolating engrafted islets from immune attack. The idea was to encapsulate islets within functional coats made from PEG hydrogel. These coats would act as a mechanical barrier against immune cells but would nonetheless allow the diffusion of nutrients and water.

To realise photopolymerisation of the PEG hydrogel, researchers established a mathematical model for controlling the thickness and permeability of the membrane. Subsequently, they functionalised the generated coats with different molecules.

Coating with glucagon-like peptide-1 or other insulinotropic agents was used as a means of reducing the number of islets required for transplantation. In addition to peptides, PEG hydrogels were coated with mesenchymal stem cells or regulatory T cells for local immunoprotection. Islet function within these hydrogel coats was preserved as indicated through insulin and viability assays.

The next step in the DMIOL work would be to test these microencapsulated islets in larger mammals, non-human primates, and finally humans. The approach has the potential to lead to immunosuppression-free transplantation, and provide a viable alternative treatment for diabetes.