title: Transferable neuronal mini-cultures to accelerate screening in primary and induced pluripotent stem cell-derived neurons.
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.
authors: 1] UNC/NCSU Joint Department of Biomedical Engineering [2] UNC Neuroscience Center.
authors: Mark
authors: M
authors: Niedringhaus
authors: 1] UNC Neuroscience Center [2] UNC Human Pluripotent Stem Cell Core [3] UNC Department of Genetics.
authors: Raluca
authors: R
authors: Dumitru
authors: 1] UNC Department of Cell Biology and Physiology [2] UNC Neuroscience Center.
authors: Angela M
authors: AM
authors: Mabb
authors: UNC Department of Chemistry.
authors: Yuli
authors: Y
authors: Wang
authors: 1] UNC Department of Cell Biology and Physiology [2] UNC Neuroscience Center [3] Carolina Institute for Developmental Disabilities.
authors: Benjamin D
authors: BD
authors: Philpot
authors: 1] UNC/NCSU Joint Department of Biomedical Engineering [2] UNC Department of Chemistry.
authors: Nancy L
authors: NL
authors: Allbritton
authors: 1] UNC/NCSU Joint Department of Biomedical Engineering [2] UNC Neuroscience Center [3] Carolina Institute for Developmental Disabilities.
authors: Anne Marion
authors: AM
authors: Taylor
mesh_terms: D000818:Animals; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D051379:Mice; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D061251:Primary Cell Culture / Q000379:methods*