Development of a human induced pluripotent stem cell-derived ovarian support cell clinical grade product for in vitro fertilization
Human induced pluripotent stem cells (hiPSCs) show promise in the development of novel strategies to alleviate reproductive diseases and improve reproductive outcomes. Here, we detail the clinical development and application of an ovarian support cell (OSC) product, Fertilo, to improve the in vitro maturation (IVM) of human oocytes. First, we demonstrate that transcription factor-mediated hiPSC differentiation produces OSCs that improve the oocyte MII maturation rate. To support clinical application, we describe raw material upgrades and the generation of clinically-suitable hiPSC Seed and Master Cell Banks, with transcriptomic analysis of resultant OSCs showing consistent and reproducible outcomes. Next, we detail analytical release testing and development of a murine oocyte maturation assay to establish product potency. Finally, application of Fertilo in a longitudinal cohort analysis shows improvement in key outcomes compared to traditional IVM. Our findings demonstrate the first-time clinical development and application of an hiPSC-derived product to promote successful reproductive outcomes. Overall design: Following batch production and cryopreservation, OSCs (final product) are analyzed by scRNA-seq