Diabetes is a disease characterised by high blood sugar due to a shortage of insulin, that affects 415 million people worldwide. Pancreatic islet transplant is an extremely promising therapy, with the potential to cure insulin-dependent diabetes. Transplant of insulin-producing cells restores natural control of blood sugar, eliminating the need for insulin, blood glucose monitoring and the risk of dangerous hypoglycaemic (low blood sugar) episodes, all of which greatly affects diabetes patients’ quality of life. Islet transplant involves purifying islets from donor pancreases and infusing them into the patient’s liver. Limitations of the therapy include:
(1) poor survival and engraftment of transplanted islets
(2) shortage of donor pancreases
(3) need for lifelong immune suppressive therapy
DRIVE developed a system (β-system) to treat severe cases of Type 1 Diabetes, by implanting a bioartificial pancreas via a minimally-invasive surgical procedure. The β-system has three main componets: a macroencapsulation device (β-shell), a biocompatible hydrogel loaded with insulin-producing cells (β-gel), and a delivery system (β-cath). The β-system still requires pre-clinical validation but showed promising results in small animal models. Some of the beneficiaries are committed to continued development towards First-in-Man Clinical Trials. DRIVE produced several results in the pursuit of the β-system, which are in a separate section. In addition to the results, more conclusions can be drawn from the research activities:
• The β-system can restore normoglycemia in a preclinical model of diabetes
• β-shells have been successfully implanted in small and large preclinical models, which responded well to the implant
• Silicone and Chronoflex implantable devices allow for a better oxygen transfer, compared to PTFE
• Additive manufacturing can generate irregular surfaces that enhance integration and vascularisation in implantable devices
• The TAP is the leading candidate implant site, due to ease of access and size of potential space
• Native HA hydrogels are a viable matrix to support implantation of live and functional cells. Addition of PFD enhances the viability of the cells through oxygen delivery
• Bioactive VEGF can be successfully linked to microspheres for controlled-release
• It is possible to produce room-temperature stable VEGF out of bacterial cultures
• Collagen from R.pulmo is a viable matrix for islet preservation
• Differentiation of iPSCs into insulin-producing cells that have the ability to respond to a glucose-challenge. Nidogen-1 seems to be instrumental for the functionality of the cells
