Generating and protecting human iPS designer islets for the treatment of type 1 diabetes

Autoimmune or Type 1 diabetes (T1D) results from the immune‐mediated destruction of insulin producing beta cells in the pancreas islets. In this proposal we will address the two most critical barriers for T1D therapy. The first is replacement of islet cell mass, derived from self‐tissue to avoid immunosuppression. We have successfully produced designer islets from stem cells to regenerate the lost islet cells. The second barrier is to control the immune system from attacking (or re‐attacking) the islets. We have successfully targeted self‐reactive immune cells to reestablish tolerance and prevent islet cell death and we will apply this technology to the designer islets generated from stem cells. Our approach arms the beta cells with molecules that will allow them to protect themselves from the immune system. Using a new humanized animal model, we will test this concept in animals first using human designer islets as a cure or to prevent T1D altogether.