Towards effective beta-cell replacement through understanding and targeting of the autoreactive immune response during onset of type 1 diabetes

Type 1 diabetes (T1D) is characterized by hyperglycemia due to autoimmune destruction of the insulin-producing beta-cells in the pancreas. The reason for this occurring is still unknown and effective therapies to halt the autoimmune response are lacking, but several promising concepts are being trialed. Regenerative medicine approaches in expanding the remaining beta cell pool, or transplanting beta cells derived from stem cells are other options trialed. Lessons learned from the study of immune regulation in T1D could be applied to immunosuppression in transplantation of beta cells derived from stem cell sources to avoid recurring autoimmunity. In this review, immunological issues in beta cell replacement therapies are discussed along possible treatment avenues such as genetically modified grafts to evade immune responses, novel immunosuppressive protocols, and the harnessing of endogenous pools of regulatory immune cell subsets. Looking into promising treatments for T1D may lead to effective immunosuppressive regimens also for beta-cell grafts from stem cells where recurring autoimmunity is a major issue to address.