U.S. Department of Health and Human ServicesHHS National Institutes of HealthNIH National Center for Advancing Translational SciencesNCATS

A versatile polypharmacology platform promotes cytoprotection and viability of human pluripotent and differentiated cells

Posted on April 29th, 2021 by Hannah Baskir

Yu Chen1,2, Carlos A. Tristan1,2, Lu Chen1, Vukasin M. Jovanovic1, Claire Malley1, Pei-Hsuan Chu1, Seungmi Ryu1, Tao Deng1, Pinar Ormanoglu1, Dingyin Tao1, Yuhong Fang1, Jaroslav Slamecka1, Hyenjong Hong1, Christopher A. LeClair1, Sam Michael1, Christopher P. Austin1, Anton Simeonov1, and Ilyas SingeƧ1

  1. National Center for Advancing Translational Sciences (NCATS), Stem Cell Translation Laboratory (SCTL), National Institutes of Health (NIH), Rockville, MD, USA.
  2. These authors contributed equally: Yu Chen, Carlos A. Tristan.


Human pluripotent stem cells (hPSCs) are capable of extensive self-renewal yet remain highly sensitive to environmental perturbations in vitro, posing challenges to their therapeutic use. There is an urgent need to advance strategies that ensure safe and robust long-term growth and functional differentiation of these cells. Here, we deployed high-throughput screening strategies to identify a small-molecule cocktail that improves viability of hPSCs and their differentiated progeny. The combination of chroman 1, emricasan, polyamines, and trans-ISRIB (CEPT) enhanced cell survival of genetically stable hPSCs by simultaneously blocking several stress mechanisms that otherwise compromise cell structure and function. CEPT provided strong improvements for several key applications in stem-cell research, including routine cell passaging, cryopreservation of pluripotent and differentiated cells, embryoid body (EB) and organoid formation, single-cell cloning, and genome editing. Thus, CEPT represents a unique poly-pharmacological strategy for comprehensive cytoprotection, providing a rationale for efficient and safe utilization of hPSCs.