Induced pluripotency in the context of stem cell expansion bioprocess development, optimization, and manufacturing: a roadmap to the clinic

Abstract

The translation of laboratory-scale bioprocess protocols and technologies to industrial scales and the application of human induced pluripotent stem cell (hiPSC) derivatives in clinical trials globally presents optimism for the future of stem-cell products to impact healthcare. However, while many promising therapeutic approaches are being tested in pre-clinical studies, hiPSC-derived products currently account for a small fraction of active clinical trials. The complexity and volatility of hiPSCs present several bioprocessing challenges, where the goal is to generate a sufficiently large, high-quality, homogeneous population for downstream differentiation—the derivatives of which must retain functional efficacy and meet regulatory safety criteria in application. It is argued herein that one of the major challenges currently faced in improving the robustness of routine stem-cell biomanufacturing is in utilizing continuous, meaningful assessments of molecular and cellular characteristics from process to application. This includes integrating process data with biological characteristic and functional assessment data to model the interplay between variables in the search for global optimization strategies. Coupling complete datasets with relevant computational methods will contribute significantly to model development and automation in achieving process robustness. This overarching approach is thus crucially important in realizing the potential of hiPSC biomanufacturing for transformation of regenerative medicine and the healthcare industry.