The Convergence of Stem Cell Technologies and Phenotypic Drug Discovery

Alexandra Friese; Andrei Ursu; Andreas Hochheimer; Hans R Schöler; Herbert Waldmann; Jan M Bruder

doi:10.1016/j.chembiol.2019.05.007

The Convergence of Stem Cell Technologies and Phenotypic Drug Discovery

Cell Chem Biol. 2019 Aug 15;26(8):1050-1066. doi: 10.1016/j.chembiol.2019.05.007. Epub 2019 Jun 20.

Authors

Alexandra Friese¹, Andrei Ursu², Andreas Hochheimer³, Hans R Schöler⁴, Herbert Waldmann⁵, Jan M Bruder⁶

Affiliations

¹ Department of Chemical Biology, Max Planck Institute of Molecular Physiology, 44227 Dortmund, Germany.
² Department of Chemical Biology, Max Planck Institute of Molecular Physiology, 44227 Dortmund, Germany; Department of Chemistry, The Scripps Research Institute, Jupiter, FL 33458, USA; Faculty of Chemistry and Chemical Biology, TU Dortmund, Otto-Hahn-Str. 4a, 44227 Dortmund, Germany.
³ ISAR Bioscience GmbH, Institute for Stem Cell & Applied Regenerative Medicine Research, 82152 Planegg, Germany.
⁴ Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany; Medical Faculty, University of Münster, Domagkstrasse 3, 48149 Münster, Germany. Electronic address: office@mpi-muenster.mpg.de.
⁵ Department of Chemical Biology, Max Planck Institute of Molecular Physiology, 44227 Dortmund, Germany; Faculty of Chemistry and Chemical Biology, TU Dortmund, Otto-Hahn-Str. 4a, 44227 Dortmund, Germany. Electronic address: herbert.waldmann@mpi-dortmund.mpg.de.
⁶ Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany. Electronic address: jan.bruder@mpi-muenster.mpg.de.

PMID: 31231030
DOI: 10.1016/j.chembiol.2019.05.007

Abstract

Recent advances in induced pluripotent stem cell technologies and phenotypic screening shape the future of bioactive small-molecule discovery. In this review we analyze the impact of small-molecule phenotypic screens on drug discovery as well as on the investigation of human development and disease biology. We further examine the role of 3D spheroid/organoid structures, microfluidic systems, and miniaturized on-a-chip systems for future discovery strategies. In highlighting representative examples, we analyze how recent achievements can translate into future therapies. Finally, we discuss remaining challenges that need to be overcome for the adaptation of the next generation of screening approaches.

Keywords: drug discovery; iPSCs; phenotypic screening; small molecules; stem cells.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Cell Culture Techniques*
Drug Discovery*
Drug Evaluation, Preclinical
Humans
Induced Pluripotent Stem Cells / cytology*
Microfluidic Analytical Techniques
Organoids / chemistry
Phenotype
Small Molecule Libraries / chemistry*
Spheroids, Cellular / chemistry

Substances

Small Molecule Libraries