ABSTRACT:
As of 2026, the transition from managing diabetes to reversing its pathophysiology has gained significant momentum through advancements in gene therapy and regenerative medicine. The field is currently defined by two major breakthroughs: the successful clinical application of stem cell-derived islet-like cells (e.g., zimislecel) and the use of CRISPR-based genome editing to create "hypoimmune" or "stealth" cells that evade autoimmune destruction without the need for systemic immunosuppression. In Type 1 Diabetes (T1D), regenerative strategies focus on replacing lost $\beta$-cell mass through the transplantation of fully differentiated, insulin-secreting cells into novel sites like the rectus abdominis sheath, which enhances graft survival and monitoring. For Type 2 Diabetes (T2D), gene therapy is exploring the in vivo reprogramming of alpha cells or non-pancreatic tissues into functional "pseudo-$\beta$-cells" and the delivery of insulin-sensitizing genes via viral vectors. Despite persistent hurdles—such as ensuring long-term graft vascularization and mitigating the risk of teratoma formation—the integration of precision gene editing and biomaterial-based encapsulation represents the most viable pathway toward a functional cure, fundamentally altering the therapeutic horizon from lifelong insulin dependency to biological restoration.