PT  - JOURNAL ARTICLE
AU  - Yu Chen
AU  - Carlos A. Tristan
AU  - Lu Chen
AU  - Vukasin M. Jovanovic
AU  - Claire Malley
AU  - Pei-Hsuan Chu
AU  - Seungmi Ryu
AU  - Tao Deng
AU  - Pinar Ormanoglu
AU  - Dingyin Tao
AU  - Yuhong Fang
AU  - Jaroslav Slamecka
AU  - Christopher A. LeClair
AU  - Sam Michael
AU  - Christopher P. Austin
AU  - Anton Simeonov
AU  - Ilyas Singeç
TI  - A Versatile Polypharmacology Platform Promotes Cytoprotection and Viability of Human Pluripotent and Differentiated Cells
AID  - 10.1101/815761
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 815761
4099  - http://biorxiv.org/content/early/2019/10/22/815761.short
4100  - http://biorxiv.org/content/early/2019/10/22/815761.full
AB  - Clinical translation of human pluripotent stem cells (hPSCs) requires advanced strategies that ensure safe and robust long-term growth and functional differentiation. Pluripotent cells are capable of extensive self-renewal, yet remain highly sensitive to environmental perturbations in vitro, posing challenges to their therapeutic use. Here, we deployed innovative high-throughput screening strategies to identify a small molecule cocktail that dramatically improves viability of hPSCs and their differentiated progeny. We discovered that 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. In proof-of-principle experiments we then demonstrated the strong improvements that CEPT provided for several key applications in stem cell research, including routine cell passaging, cryopreservation 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 polypharmacology 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.