Timothy J. Kieffer1,2, Corinne A. Hoesli3,4 and A.M. James Shapiro5,6,7 1Department of Cellular and Physiological Sciences, Life Sciences Institute, School of Biomedical Engineering 2Department of Surgery, The University of British Columbia, Vancouver V6T1Z3, British Columbia, Canada 3Department of Chemical Engineering, Department of Biomedical Engineering, McGill University, Montreal H3A 0C5, Québec, Canada 4Associate Member, Department of Biomedical Engineering, McGill University, Montreal H3A 0C5, Québec, Canada 5Clinical Islet Transplant Program, University of Alberta, Edmonton T6G2E1, Alberta, Canada; 6Department of Surgery, University of Alberta, Edmonton T6G2E1, Alberta, Canada; 7Alberta Diabetes Institute, University of Alberta, Edmonton T6G2E1, Alberta, Canada Correspondence: tim.kiefferubc.ca

β-Cell replacement for type 1 diabetes (T1D) can restore normal glucose homeostasis, thereby eliminating the need for exogenous insulin and halting the progression of diabetes complications. Success in achieving insulin independence following transplantation of cadaveric islets fueled academic and industry efforts to develop techniques to mass produce β cells from human pluripotent stem cells, and these have now been clinically validated as an alternative source of regulated insulin production. Various encapsulation strategies are being pursued to contain implanted cells in a retrievable format, and different implant sites are being explored with some strategies reaching clinical studies. Stem cell lines, whether derived from embryonic sources or reprogrammed somatic cells, are being genetically modified for designer features, including immune evasiveness to enable implant without the use of chronic immunosuppression. Although hurdles remain in optimizing large-scale manufacturing, demonstrating efficacy, durability, and safety, products containing stem cell–derived β cells promise to provide a potent treatment for insulin-dependent diabetes.