A Modular Biomanufacturing and Cryopreservation Platform for Scalable Production of Clinical-Grade Stem Cell Therapies

About This Grant

Human induced pluripotent stem cells (hiPSCs) are a foundational technology for regenerative medicine, disease modeling, and cell-based therapies. However, the clinical translation of hiPSC-derived therapeutics is constrained by unresolved challenges in manufacturing scalability, product consistency, and long-term storage. Current production methods, such as static culture or stirred-tank bioreactors, either lack throughput or impose damaging shear forces that compromise cell viability and stemness. Additionally, existing cryopreservation strategies are not optimized for the large-volume required for centralized manufacturing and distributed clinical deployment. To address these bottlenecks, we propose to develop a modular, low-shear, perfusion-based biomanufacturing platform coupled with controlled-rate cryopreservation for scalable and reproducible expansion of hiPSCs. This R21 will establish the technical feasibility and foundational workflows for a generalizable manufacturing system suitable for diverse therapeutic applications. In Aim 1, we will engineer and optimize a multilayer, perfusion-based bioreactor system to support hiPSC expansion at clinical scales. We will define operational parameters, evaluate multiple hiPSC lines, and develop protocols for efficient harvesting and redeployment. In Aim 2, we will implement long-term culture strategies to preserve genomic stability and pluripotency across multiple passages and optimize cryopreservation workflows using cryobags and controlled-rate freezing. Post-thaw cells will be assessed for viability, genomic integrity, and differentiation potential. Successful completion of this project will yield the first integrated platform for low-shear, current Good Manufacturing Practice (cGMP)-compatible expansion and cryostorage of hiPSC-derived therapeutic products. This innovation will reduce production variability, enhance scalability, and enable rapid deployment of hiPSC-based therapies across a range of disease indications. The resulting system will serve as a flexible and translational foundation for future commercial partnerships and larger-scale studies, consistent with the high- risk, high-reward goals of the R21 mechanism.