Project description

About Xenoislet

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.

Source: https://www.google.hu/search?q=type+1+diabetes+mellitus&client=firefox-b&source=lnms&tbm=isch&sa=X&ved=0ahUKEwjT5JK8_a7PAhVEOBQKHTnnDokQ_AUICCgB&biw=1536&bih=731&dpr=1.25#imgrc=SB2uyv2Nw37ZJM%3A

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

  1. Selection of a pig line fulfilling the safety requirement of xenotransplantation of pig insulinproducing cells into humans.
  2. Development of Quality Control (QC) and Standard Operating Procedure (SOP) for production of pig pancreatic patches.
  3. 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)
  4. 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

Topics addressed

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

Project coordinator

Prof. Pierre Gianello, Universite, Catholique de Louvain (UCL), Belgium

Project duration

1st September 2013 - 31st August 2017

Project budget: 6,396,946.52 EUR


EU funding: 5,037,148.00 EUR


Partners

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)/

 

This project has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no. 601827