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Sci Rep. 2015 Feb 10;5:8353. doi: 10.1038/srep08353.

Transferable neuronal mini-cultures to accelerate screening in primary and induced pluripotent stem cell-derived neurons.

Author information

1
1] UNC/NCSU Joint Department of Biomedical Engineering [2] UNC Neuroscience Center.
2
1] UNC Neuroscience Center [2] UNC Human Pluripotent Stem Cell Core [3] UNC Department of Genetics.
3
1] UNC Department of Cell Biology and Physiology [2] UNC Neuroscience Center.
4
UNC Department of Chemistry.
5
1] UNC Department of Cell Biology and Physiology [2] UNC Neuroscience Center [3] Carolina Institute for Developmental Disabilities.
6
1] UNC/NCSU Joint Department of Biomedical Engineering [2] UNC Department of Chemistry.
7
1] UNC/NCSU Joint Department of Biomedical Engineering [2] UNC Neuroscience Center [3] Carolina Institute for Developmental Disabilities.

Abstract

The effort and cost of obtaining neurons for large-scale screens has limited drug discovery in neuroscience. To overcome these obstacles, we fabricated arrays of releasable polystyrene micro-rafts to generate thousands of uniform, mobile neuron mini-cultures. These mini-cultures sustain synaptically-active neurons which can be easily transferred, thus increasing screening throughput by >30-fold. Compared to conventional methods, micro-raft cultures exhibited significantly improved neuronal viability and sample-to-sample consistency. We validated the screening utility of these mini-cultures for both mouse neurons and human induced pluripotent stem cell-derived neurons by successfully detecting disease-related defects in synaptic transmission and identifying candidate small molecule therapeutics. This affordable high-throughput approach has the potential to transform drug discovery in neuroscience.

PMID:
25666972
PMCID:
PMC4322355
DOI:
10.1038/srep08353
[Indexed for MEDLINE]
Free PMC Article

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