Evidence map›Paper›PMID 26392547›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2015

Human pluripotent stem cell-derived neural constructs for predicting neural toxicity.

Michael P Schwartz, Zhonggang Hou, Nicholas E Propson, Jue Zhang, Collin J Engstrom, Vitor Santos Costa, Peng Jiang, Bao Kim Nguyen, Jennifer M Bolin, William Daly and 5 more

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 153 papers.

0numbers the graph read from it
0cells of the map it votes in
153citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

153 citing papers in PubMed.

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  19. Brain organoids: A new tool for modelling of neurodevelopmental disorders.Journal of cellular and molecular medicine · 2024
    Review
  20. Article

93 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Michael P SchwartzDepartment of Biomedical Engineering, University of Wisconsin, Madison, WI 53706;
Zhonggang HouRegenerative Biology, Morgridge Institute for Research, Madison, WI 53715;
Nicholas E PropsonRegenerative Biology, Morgridge Institute for Research, Madison, WI 53715;
Jue ZhangRegenerative Biology, Morgridge Institute for Research, Madison, WI 53715;
Collin J EngstromDepartment of Biostatistics and Medical Informatics, University of Wisconsin, Madison, WI 53792; Department of Computer Sciences, University of Wisconsin, Madison, WI 53706;
Vitor Santos CostaCenter for Research in Advanced Computing Systems, Institute for Systems and Computer Engineering, Technology and Science, and Department of Computer Science, Faculty of Sciences, University of Porto, Porto 4169-007, Portugal;
Peng JiangRegenerative Biology, Morgridge Institute for Research, Madison, WI 53715;
Bao Kim NguyenRegenerative Biology, Morgridge Institute for Research, Madison, WI 53715;
Jennifer M BolinRegenerative Biology, Morgridge Institute for Research, Madison, WI 53715;
William DalyDepartment of Biomedical Engineering, University of Wisconsin, Madison, WI 53706;
Yu WangRegenerative Biology, Morgridge Institute for Research, Madison, WI 53715;
Ron StewartRegenerative Biology, Morgridge Institute for Research, Madison, WI 53715;
C David PageDepartment of Biostatistics and Medical Informatics, University of Wisconsin, Madison, WI 53792; Department of Computer Sciences, University of Wisconsin, Madison, WI 53706;
William L MurphyDepartment of Biomedical Engineering, University of Wisconsin, Madison, WI 53706; Department of Orthopedics and Rehabilitation, University of Wisconsin, Madison, WI 53705;
James A ThomsonRegenerative Biology, Morgridge Institute for Research, Madison, WI 53715; Department of Cell and Regenerative Biology, University of Wisconsin, Madison, WI 53705; Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA 93106 jthomson@morgridge.org.

Funding

Retinal tissue chips for ocular disease modelingUH3TR000506 · NCATS · MORGRIDGE INSTITUTE FOR RESEARCH, INC. · PI THOMSON, JAMES ALEXANDER · 2014 to 2016
$6.2M
Human iPS/ES Cell-Based Models for Predictive Neural Toxicity and TeratogenicityUH2TR000506 · NCATS · MORGRIDGE INSTITUTE FOR RESEARCH, INC. · PI THOMSON, JAMES ALEXANDER · 2012 to 2013
$2.4M
Probing biochemical/biophysical influences on endothelial-mesenchymal transitionR21EB016381 · NIBIB · UNIVERSITY OF WISCONSIN-MADISON · PI MURPHY, WILLIAM L., SCHWARTZ, MICHAEL PAUL · 2013 to 2014
$399k
NCATS NIH HHS 1UH2TR000506-01NCATS NIH HHS 3UH2TR000506-02S1NCATS NIH HHS 4UH3TR000506-03NCATS NIH HHS UH2 TR000506NCATS NIH HHS UH3 TR000506NIBIB NIH HHS R21 EB016381NIBIB NIH HHS R21EB016381-01
6 · The paper itself

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.

Indexed as

Cell DifferentiationBrainCell CommunicationCells, CulturedCulture Media, Serum-FreeEmbryonic Stem CellsEndothelial CellsGene Expression Regulation, DevelopmentalGene OntologyHumansHydrogelsMacrophagesMesenchymal Stem CellsMicrogliaModels, BiologicalNeural Stem CellsCulture Media, Serum-FreeHydrogelsPolyethylene GlycolsXenobioticsdifferentiationmachine learningorganoidtissue engineeringtoxicology

Identifiers

PMID26392547
PMCPMC4603492

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.