• Hypoimmune stem cell-derived β cells offer a promising strategy to overcome immune rejection without systemic immunosuppression, potentially expanding islet transplantation accessibility.
• Genetic engineering of β cells to evade immune detection leverages insights from immune regulation pathways, aiming to protect grafts while preserving systemic immunity.
• Current alternative strategies like encapsulation and co-transplantation face limitations in immune isolation and graft survival, highlighting the need for genetic hypoimmunity.
• Future research should explore genetic targets inspired by immune-evasive primary islets and CAR T cells to enhance safety and efficacy of β cell replacement therapy.