Differentiation and Encapsulation of ß-like cells for the treatment of type 1 Diabetes Mellitus

Candidate

Myriam NEUMANN

Promoters

Prof. Bao-Lian SU, Department of chemistry, NISM, Laboratory of Chemistry of Inorganic Materials (CMI)

Prof. Thierry ARNOULD, Department of biology, NARILIS, Laboratory of Cellular and Molecular Biology (URBC)

Jury

• Prof. Stéphane VINCENT (département de chimie, UNamur), président
• Prof. Bao-Lian SU (département de chimie, UNamur), promoteur
• Prof. Thierry ARNOULD (département de biologie, UNamur), promoteur
• Prof. Patricia RENARD (département de biologie, UNamur)
• Prof. Jean-Paul THISSEN (EDIN, UClouvain)
• Prof. Amin SHAVANDI (Ecole Polytechnique de Bruxelles, ULB)

Summary

Type 1 diabetes mellitus is an auto-immune disease causing the T-cell mediated destruction of insulin-producing β-cells, resulting in chronic hyperglycemia. Current treatments such as insulin replacement therapy or the transplantation of pancreas or pancreatic islets present major disadvantages such as the constant need of drugs, as well as a shortage of donor organs. The encapsulation of stem cell-derived β-cells in a semi-permeable membrane with selective diffusion properties could offer a sustainable solution to overcome these limitations.

Huge progress in the domain of regenerative medicine has been made in the last decades thanks to the discovery of stem cells and their capacity to self-renew and to differentiate into various specialized cell types. The first objective of this research is the differentiation of human induced Pluripotent Stem Cells (hiPSCs) into new functional glucose-responsive, insulin secreting β-cells. The obtained therapeutic cells are subsequently encapsulated in order to shield them from the host immune cell responders and avoid the need for immune-suppressive treatments. Main criteria for these encapsulation materials are a good biocompatibility, adapted stability and a selective diffusion of essential metabolites such as glucose and insulin whilst providing immune-protection. The second objective is thus the development of an adapted hybrid material combining the advantages of very biocompatible biopolymers and highly tunable inorganic polymers such as silica and titania. For the synthesis of these core/shell microcapsules, a microfluidic synthesis based on a double emulsion principle is currently developed. The transplantation of the formed microcapsules could counterbalance the lack of insulin due to deficient cells and restore proper glycaemia regulation.