Title: Macroencapsulated Porcine Pancreatic Islets to cure Diabetes Mellitus type 1/2
EU FP7 Collaborative Project (small or medium-scale focused research project)
Objectives: During the last five years, within the EU FP6 Integrated Project XENOME (LSHB-CT-2006-037377), we have convincingly demonstrated in primates that a complete control of induced type 1 diabetes is routinely obtained for 6/8 months after transplantation of subcutaneous alginate macroencapsulated porcine islets xenograft without the use of any immunosuppression. In order to improve the function of pig islets, we have produced with AVANTEA a transgenic pig expressing GLP-1 at the level of the pig islets. In fact, GLP1 is not only able to (i) increase the insulin gene expression and insulin biosynthesis, but also to (ii) induce the replication of islet cells and promotes islet-cell neogenesis and (iii) protect islets cells from apoptosis. GLP-1 has already demonstrated its in vivo potential to improve insulin secretion in subjects with impaired glucose tolerance and type 2 diabetes.
The main objectives of this three-year project will therefore be (1) to evaluate in vitro the effect of GLP1 transgene expression in pig islets after hyperglycaemic challenge; (2) to continue to produce transgenic pigs specifically expressing GLP-1 in pig islets under insulin promoter, and (3) finally to test these modified pig islets in our well characterized pig-to-diabetic primates model in vivo. However, in order to use islets from newborn unmodified or transgenic pigs, we will also set up (4) the pig islets isolation and cell maturation technique for Neonates Pancreatic Pig Cluster cells since neonates pig islets have prolonged survival and would also render possible the use of Designed Pathogen Free (DPF) neonates pigs which will represent a key point to reach clinical studies.