High-Throughput Toxicity and Phenotypic Screening of 3D Human Neural Progenitor Cell Cultures on a Microarray Chip Platform

Gregory J Nierode; Brian C Perea; Sean K McFarland; Jorge F Pascoal; Douglas S Clark; David V Schaffer; Jonathan S Dordick

doi:10.1016/j.stemcr.2016.10.001

High-Throughput Toxicity and Phenotypic Screening of 3D Human Neural Progenitor Cell Cultures on a Microarray Chip Platform

Stem Cell Reports. 2016 Nov 8;7(5):970-982. doi: 10.1016/j.stemcr.2016.10.001. Epub 2016 Oct 27.

Authors

Gregory J Nierode¹, Brian C Perea², Sean K McFarland³, Jorge F Pascoal⁴, Douglas S Clark², David V Schaffer⁵, Jonathan S Dordick⁶

Affiliations

¹ Chemical and Biological Engineering and Center for Biotechnology & Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
² Chemical and Biomolecular Engineering, University of California, Berkeley, CA 94720, USA.
³ Bioengineering, University of California, Berkeley, CA 94720, USA.
⁴ Department of Bioengineering and Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Lisbon 1049-001, Portugal.
⁵ Chemical and Biomolecular Engineering, University of California, Berkeley, CA 94720, USA; Bioengineering, University of California, Berkeley, CA 94720, USA.
⁶ Chemical and Biological Engineering and Center for Biotechnology & Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA. Electronic address: [email protected].

Abstract

A 3D cell culture chip was used for high-throughput screening of a human neural progenitor cell line. The differential toxicity of 24 compounds was determined on undifferentiated and differentiating NPCs. Five compounds led to significant differences in IC₅₀ values between undifferentiated and differentiating cultures. This platform has potential use in phenotypic screening to elucidate molecular toxicology on human stem cells.

Keywords: high-content screening; high-throughput microarray; human neural stem cells; neurotoxicity; screening; three-dimensional cell culture.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Cell Culture Techniques
Cell Differentiation / drug effects
Cell Differentiation / genetics
Cell Survival / drug effects
Cell Survival / genetics
Dose-Response Relationship, Drug
Drug Discovery*
High-Throughput Screening Assays*
Humans
Neural Stem Cells / cytology
Neural Stem Cells / drug effects*
Neural Stem Cells / metabolism*
Oligonucleotide Array Sequence Analysis
Phenotype*
Toxicity Tests, Acute

Grants and funding

R01 ES020903/ES/NIEHS NIH HHS/United States