Immunological Issues After Stem Cell-Based β Cell Replacement

Islet and pancreas transplantation prove that β cell replacement can cure the glycemic derangements in type 1 diabetes (T1D). Induced pluripotent stem cells (iPSCs) can differentiate into functional insulin-producing cells, able to restore normoglycemia in diabetic animal models. iPSCs in particular can be derived from the somatic cells of a person with T1D. This review aims to clarify if it is possible to transplant autologous iPSC-derived β cells without immunosuppression or which are the alternative approaches.

Several lines of evidence show that autologous iPSC and their derivatives can be immune rejected, and this immunogenicity depends on the reprogramming, the type of cells generated, the transplantation site, and the genetic/epigenetic modifications induced by reprogramming and differentiation. Besides, cell replacement in T1D should keep in consideration also the possibility of autoimmune reaction against autologous stem cell-derived β cells. Autologous iPSC-derived β cells could be immunogenic upon transplantation, eliciting both auto and allogeneic immune response. A strategy to protect cells from immune rejection is still needed. This strategy should be efficacious in protecting the grafted cells, but also avoid toxicity and the risk of tumor formation.