The Xenoislet project aims to enable successful transplantation of pig insulin-producing cells into human type 1 diabetes mellitus (T1DM) patients by using pig transgenesis and alginate macroencapsulation. The project is focusing on to improve, standardise and test the porcine pancreatic islet xenotransplantation technology into primates and make it ready for pilot clinical trials and major Venture Capital investment or immediate uptake by large industry at the end of the project.
Concept and objectives
Pig islets represent a promising alternative to human islet transplantation in diabetic patients since they can be obtained in large quantities without raising ethical questions and they have been shown to meet the physiological needs in large animal models. But pig islets provide a lower response than human beta cells to glucose challenge. So the introduction of transgenes like glucoincretin hormone glucagon-like peptide (GLP-1) protein is necessary to obtain pancreatic pig islets which respond to glucose challenge in the same physiological manner as humans. The use of xenogeneic cells, however, raises a major difficulty which is the need for a heavy systemic immunosuppression (IS). In order to avoid this heavy IS, mechanical immunoprotection is developed: encapsulation in a subcutaneous alginate patch.
Main steps of Xenoislet
- Selection of a pig line fulfilling the safety requirement of xenotransplantation of pig insulinproducing cells into humans.
- Development of Quality Control (QC) and Standard Operating Procedure (SOP) for production of pig pancreatic patches.
- Production of a genetically engineered pig expressing GLP1 proteins and Muscarinic receptor 3 (MR3) at the level of pig islets (under a pig insulin promoter)
- Whether Designed Pathogen Free (DPF) pig colony is selected and approved by regulator, then a pilot study in humans could be initiated at the end of XENOISLET project after having obtained Ethical Committee, National and EMA approvals, submission of IMPD and after procedures are standardized.
|WP1||Pig genetic engineering and breeding for the expression of genes of interest in islet|
|WP2||In vitro studies:culture and maturation of NPPCs islets. Standardization to meet clinical requirement|
|WP3||Use of unmodified and GLP1/M3R transgenic NPPC clusters to correct diabetes|
|WP4||Development of safety procedures to drive “product”-pig cellular grafting- to human clinical trial|
|WP5||Scientific coordination and management. Regulatory Issues|
|WP6||Business Development: Project company, IP and know-how valorisation, dissemination|
|WP7||Pilot clinical study in diabetic patients: end point “safety”|
Project full title
Macroencapsulated Porcine Pancreatic Islets to cure Diabetes Mellitus type ½
HEALTH.2013.0-1 HEALTH.2013.0-1- Boosting the translation of health research projects’ results into innovative applications for health; Boosting the translation of health research projects’ results into innovative applications for health
Prof. Pierre Gianello, Universite, Catholique de Louvain (UCL), Belgium
1st September 2013 - 31st August 2017
Project budget: 6,396,946.52 EUR
EU funding: 5,037,148.00 EUR
2 academic research organisations /Universite Catholique de Louvain (UCL), The Glasgow Caledonian University (GCU)/; 3 Small and Medium Enterprises /Avantea srl (AVT), BioTalentum Ltd (BIOT), AVIDIN Ltd (AVD)/