Human pluripotent stem cell-derived neural constructs for predicting neural toxicity
Human pluripotent stem cell-derived neural constructs for predicting neural toxicity
dc.contributor.author | Schwartz,MP | en |
dc.contributor.author | Hou,ZG | en |
dc.contributor.author | Propson,NE | en |
dc.contributor.author | Zhang,J | en |
dc.contributor.author | Engstrom,CJ | en |
dc.contributor.author | Vítor Santos Costa | en |
dc.contributor.author | Jiang,P | en |
dc.contributor.author | Nguyen,BK | en |
dc.contributor.author | Bolin,JM | en |
dc.contributor.author | Daly,W | en |
dc.contributor.author | Wang,Y | en |
dc.contributor.author | Stewart,R | en |
dc.contributor.author | Page,CD | en |
dc.contributor.author | Murphy,WL | en |
dc.contributor.author | Thomson,JA | en |
dc.date.accessioned | 2018-01-19T01:31:27Z | |
dc.date.available | 2018-01-19T01:31:27Z | |
dc.date.issued | 2015 | en |
dc.description.abstract | Human pluripotent stem cell-based in vitro models that reflect human physiology have the potential to reduce the number of drug failures in clinical trials and offer a cost-effective approach for assessing chemical safety. Here, human embryonic stem (ES) cell-derived neural progenitor cells, endothelial cells, mesenchymal stem cells, and microglia/macrophage precursors were combined on chemically defined polyethylene glycol hydrogels and cultured in serum-free medium to model cellular interactions within the developing brain. The precursors self-assembled into 3D neural constructs with diverse neuronal and glial populations, interconnected vascular networks, and ramified microglia. Replicate constructs were reproducible by RNA sequencing (RNA-Seq) and expressed neurogenesis, vasculature development, and microglia genes. Linear support vector machines were used to construct a predictive model from RNA-Seq data for 240 neural constructs treated with 34 toxic and 26 nontoxic chemicals. The predictive model was evaluated using two standard hold-out testing methods: a nearly unbiased leave-one-out cross-validation for the 60 training compounds and an unbiased blinded trial using a single hold-out set of 10 additional chemicals. The linear support vector produced an estimate for future data of 0.91 in the cross-validation experiment and correctly classified 9 of 10 chemicals in the blinded trial. | en |
dc.identifier.uri | http://repositorio.inesctec.pt/handle/123456789/7023 | |
dc.identifier.uri | http://dx.doi.org/10.1073/pnas.1516645112 | en |
dc.language | eng | en |
dc.relation | 5129 | en |
dc.rights | info:eu-repo/semantics/openAccess | en |
dc.title | Human pluripotent stem cell-derived neural constructs for predicting neural toxicity | en |
dc.type | article | en |
dc.type | Publication | en |
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