Scalable Bioreactor-Based Suspension Approach to Generate Stem Cell-Derived Islets From Healthy Donor-Derived iPSCs

This publication evaluates a suspension differentiation process for producing islet-like cells from healthy donor-derived human induced pluripotent stem cells in 0.1 L Vertical-Wheel bioreactors. Stagewise characterization included pancreatic and endocrine markers, gene expression, electrophysiology, oxygen consumption, insulin secretion, transplantation, graft histology, yield, and process cost. The workflow generated 90.4% PDX1 and NKX6.1 double-positive pancreatic progenitors and glucose-responsive islet-like cells, although ductal, enterochromaffin, and other off-target populations were identified. The bioreactor process produced approximately 105 million cells per vessel, a 12.7-fold increase over the semi-planar protocol evaluated in the study. It also reduced the calculated cost of generating the study’s target cell mass by 88.8%. Transplanted products matured in vivo and reversed diabetes in the tested mouse model.