A Versatile Polypharmacology Platform Promotes Cytoprotection and Viability of Human Pluripotent and Differentiated Cells

Overview

Journal Nat Methods

Specialties Biomedical Engineering
Pathology

Date 2021 May 4

PMID 33941937

Citations 60

Authors

Yu Chen

Carlos A Tristan

Lu Chen

Vukasin M Jovanovic

Claire Malley

Pei-Hsuan Chu

Seungmi Ryu

Tao Deng

Pinar Ormanoglu

Dingyin Tao

Yuhong Fang

Jaroslav Slamecka

Hyenjong Hong

Christopher A LeClair

Sam Michael

Christopher P Austin

Anton Simeonov

Ilyas Singec

Affiliations

Soon will be listed here.

Abstract

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.

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