Optimisation of Allogeneic GMP Grade Mesenchymal Stromal Cells To Promote The Long Term Engraftment And Function Of Islets

Islets are clusters of cells within the pancreas which contain insulin producing cells. Transplantation of these cells into the liver of a patient with Type 1 diabetes, who by definition cannot produce insulin, is an established clinical intervention in those with poorly controlled diabetes. However, the treatment falls short of a cure and most patients never achieve insulin independence and insulin production of the transplanted islets decreases over time. This project will focus on improving outcomes by transplantation of islets with specific cells called mesenchymal stromal cells (MSCs) in pre-clinical models. MSCs have immunomodulatory, anti-inflammatory and pro-regenerative properties. The main aim of the project is to develop an "off-the-shelf", allogeneic MSCs from banked tissue requiring no further matching of donor to recipient.

The cell experts in SNBTS have manufactured MSCs from human tissue to Good Manufacturing Practise (GMP) grade. We have shown that the co-transplantation of these MSCs with islets improves islet transplant outcomes in a diabetic mouse model leading to a cure of the diabetes in 6 out of 8 mice that received the co-infusion in contrast to those mice that received islets alone where no cure was demonstrated (Forbes S...Mountford J et al., Science Translational Medicine, 2021). In this project the focus will be on further developing these cells for clinical use. A focus will be on: the method of delivery of these cells in our in vivo diabetic rodent model, consideration of the optimum dose and state (activated vs. non-activated) of the cells and examining their efficacy post thawing.