Chemical cytoprotection for stress-free use of human stem cells in basic and translational research

Clinical translation of human pluripotent stem cells (hPSCs) requires advanced strategies that ensure safe and robust long-term growth and functional differentiation. We recently reported the development of a new small molecule cocktail that can be used as a universal end-to-end solution for stress-free culture of human cells. This four-part small molecule cocktail, which we named CEPT (Chroman 1, Emricasan, trans-ISRIB, Polyamines), enhanced cell survival of genetically stable hPSCs by simultaneously blocking several stress mechanisms that otherwise compromise cell structure and function. CEPT improved routine cell passaging, cryopreservation/thawing of pluripotent and differentiated cells, embryoid body and organoid formation, single-cell cloning, genome editing, and new iPSC line generation. Thus, CEPT represents a unique poly-pharmacological strategy for comprehensive cytoprotection, providing a new rationale for efficient and safe utilization of hPSCs. Conferring cell fitness by multi-target drug combinations may become a common approach in cryobiology, drug development, and regenerative medicine.