Joey Lau Börjesson
Bioengineering strategies to create local protection of ß-cells after transplantation
My research has over the years been focused on β-cell physiology and β-cell replacement as therapy for type 1 diabetes. A main obstacle in β-cell replacement is immunological components hampering graft survival, where innate immune, autoimmune and allogeneic components all contribute. The research in our group is focused on creating local protection from cellular death combined with the induction of local tolerance. Thereby, the opportunity to exclude immunosuppressive drugs from β-cell replacement therapies may be achieved. This would then open the possibility for such treatment for the majority of T1D patients. Since there is a limited number of β-cells available from conventional organ donors for clinical transplantation, protocols are focused on using a renewable source of insulin-producing cells derived from human pluripotent stem cells. In our lab, we generate insulin-producing islet-like cell clusters from induced pluripotent stem cells and embryonic stem cells. The former also provides the opportunity to circumvent allogeneic reactions focusing on innate immune and possible autoimmune components. The strategies included are to diminish innate immunity reactions after transplantation by using biomaterials and/or to coat islets with protective cells such as decidual or mesenchymal stem cells before transplantation. A challenge in this effort is to identify strategies that are clinically translatable, i.e. find a modification that could be accepted as an advanced therapeutic medicinal product (ATMP).
Generation of insulin-producing islet-like cell clusters derived from human pluripotent stem cells
Figure A. Human pluripotent stem cell-derived islet-like cell clusters in culture.
Figure B. Immunostained islet-like cell cluster derived from human pluripotent stem cells.