Scaling Stem Cells to Cure Millions of Patients with Diabetes: Approaches, Technology, and Future Directions

Stem cells offer a renewable and safe source of islets to enable widespread immunosuppression-free islet cell transplantation as a potential cure for diabetes mellitus (DM). Preliminary reports from current stem cell-derived islet cell transplantation clinical trials show promise. More clinical trials are expected to report similarly favorable outcomes shortly that hope to drive stem cell-based technology from consideration into reality. Although optimization is ongoing and proof of concept from these trials is crucial before implementation becomes standard of care, early consideration of process scalability to enable accessibility for millions of patients with diabetes is vital. Planning for the success of these technologies means considering approaches, techniques, and technology early during the introduction of stem cell-derived treatments to optimize current investigation and maximize future utility. Herein, we discuss the two top contenders for stem cell-derived islet cell transplantation, inducible pluripotent stem cell-based autologous islets and allogeneic embryonic stem cell-derived islets, and evaluate their potential for scalability. Further, we introduce the current investigation of artificial intelligence approaches to optimize cell selection and differentiation. We also review two-versus-three-dimensional culture techniques and technological advances that hope to enable mass production of stem cell-derived islets in the future. Finally, we discuss an essential real-life consideration for these technologies – the cost and accessibility to the 40 million patients with DM worldwide. We intend to highlight the importance of scalability concerns early during the investigation to combat such problems and diminish potential scalability barriers in promoting early widespread stem cell accessibility to millions of patients.