Scale Up Manufacturing Approach for Production of Human Induced Pluripotent Stem Cell-Derived Islets Using Vertical Wheel Bioreactors

This publication reports a fully suspended process for expansion and six-stage differentiation of human induced pluripotent stem cells into stem cell-derived islets in 0.1 L and 0.5 L Vertical-Wheel bioreactors. A fivefold increase in vessel volume produced a twelvefold increase in islet equivalent yield, from a median of 15,005 to 183,002, without compromising islet structure. The 27-day process generated endocrine populations expressing beta-, alpha-, delta-, and other islet-cell markers, with glucose-responsive insulin secretion and transcriptomic features approaching adult islets. The authors evaluated multiple donor-derived iPSC lines, cellular heterogeneity, off-target populations, and in vitro and in vivo function. Transplanted islets reversed diabetes in all 15 treated mice by 60 days and continued to mature after engraftment, supporting further development of scalable SC-islet manufacturing processes.