Please use this identifier to cite or link to this item: http://repositorio.inesctec.pt/handle/123456789/7023
Title: Human pluripotent stem cell-derived neural constructs for predicting neural toxicity
Authors: Schwartz,MP
Hou,ZG
Propson,NE
Zhang,J
Engstrom,CJ
Vítor Santos Costa
Jiang,P
Nguyen,BK
Bolin,JM
Daly,W
Wang,Y
Stewart,R
Page,CD
Murphy,WL
Thomson,JA
Issue Date: 2015
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.
URI: http://repositorio.inesctec.pt/handle/123456789/7023
http://dx.doi.org/10.1073/pnas.1516645112
metadata.dc.type: article
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Appears in Collections:CRACS - Articles in International Journals

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