ECE2017 Symposia Beta cell replacement and plasticity (Endorsed by Endocrine Connections) (3 abstracts)
Italy.
Pluripotent stem cells (PSC), both embryonic and induced (iPSC), are the most promising cell sources for replacement therapies. In particular for a disease like type 1 diabetes (T1D), caused by the loss of a single specific cell type that does not need to be transplanted back in its originating site to perform its function, a stem cell-based cell replacement therapy seems to be the ideal cure. At present, however, a successful strategy for the use of PSC in patients with diabetes has still to overcome several important hurdles, including i) the development of in vitro differentiation protocol for β cell generation, efficient and reproducible in different cell lines in different labs, ii) the possible tumorigenicity of PSC-derived β cells, iii) the risk of allo- and auto-immune rejection upon transplantation into a subject with T1D and iv) the regulatory/economic issues associated to the use of iPSC in humans, starting from production of GMP iPSC lines. At present, the major challenge is how to avoid immune-rejection of stem cell-derived β cells. To overcome the risk of an alloimmune response we could (i) use autologous iPSC, but personalized cell therapy has big economic and safety limits or (ii) iPSC from a cell bank with a limited number of highly selected cell donors with homozygous HLA types, to enable HLA matching for a majority of potential recipients. These strategies, however, would not eliminate the recurrence of autoimmunity after a new exposure to β cell antigens of the immune system of the T1D recipient. The only possible solution consists into trying to hide the transplanted cells from the immune system: we and others are exploring the possibility to achieve this goal through i) the setup of a new immunosuppressive regimen for PSC-derived β cells, able to contrast autoimmune response; ii) the microencapsulation of cells into inert biomaterials, iii) the macroencapsulation of cells into specific devices able to protect them from allo- and auto-immune response while allowing oxygen, nutrients, and insulin exchange and iv) the genetic manipulation of the cells to escape immune recognition. If the limit of immune rejection is solved, a successful translation to the clinical practice of stem cell therapy for diabetes will be closer.