Overcoming Suspension Culture Differentiation Challenges in Bioreactors: Insights/Best Practices from Scaling hiPSC-Islet Production
Abstract
The scalable production of human induced pluripotent stem cells (hiPSCs) and their directed differentiation into pancreatic islets (hiPSC-islets) are critical for advancing modern diabetes treatment and cell-based therapies. Our study demonstrates an efficient and convenient approach to scaling up hiPSC-islet manufacturing by utilizing PBS Vertical-Wheel® bioreactors, generating transcriptionally mature, patient-derived iPSC-islets with improved functionality and yield — without multi-vessel pooling or physical manipulations. By optimizing 3D culture conditions and using small molecules in a suspension-based system, this protocol enhances stem cell proliferation, human pancreatic cell differentiation efficiency, and SC-islet maturation while maintaining key phenotypic and functional characteristics. Our key findings highlight the potential of 3D suspension bioreactor-based expansion to overcome traditional limitations in hiPSC derived therapy production, offering a single-vessel, robust, and scalable platform for future clinical and therapeutic applications. This work represents a significant step toward enabling large-scale, high-quality, and functionally mature patient-derived hiPSC derived therapy production for translational research..
Presenter: Dr. Nidheesh Dadheech, M.Sc. Ph.D, Senior Cell Therapy Research and Process Development Lead, Human iPSC-Islet Cell Therapy Manufacturing, Alberta Diabetes Institute, University of Alberta.