| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Hou, Zhonggang Thomson, James A. Engstrom, Collin J. Daly, William Wang, Yu Stewart, Ron Zhang, Jue Page, C. David Propson, Nicholas E. Schwartz, Michael P. Nguyen, Bao Kim Santos Costa, Vitor Murphy, William L. Bolin, Jennifer M. Jiang, Peng |
| Description |
Author Affiliation: Schwartz MP ( Department of Biomedical Engineering, University of Wisconsin, Madison, WI 53706); Hou Z ( Regenerative Biology, Morgridge Institute for Research, Madison, WI 53715); Propson NE ( Regenerative Biology, Morgridge Institute for Research, Madison, WI 53715); Zhang J ( Regenerative Biology, Morgridge Institute for Research, Madison, WI 53715); Engstrom CJ ( Department of Biostatistics and Medical Informatics, University of Wisconsin, Madison, WI 53792); Santos Costa V ( Center 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); Jiang P ( Regenerative Biology, Morgridge Institute for Research, Madison, WI 53715); Nguyen BK ( Regenerative Biology, Morgridge Institute for Research, Madison, WI 53715); Bolin JM ( Regenerative Biology, Morgridge Institute for Research, Madison, WI 53715); Daly W ( Department of Biomedical Engineering, University of Wisconsin, Madison, WI 53706); Wang Y ( Regenerative Biology, Morgridge Institute for Research, Madison, WI 53715); Stewart R ( Regenerative Biology, Morgridge Institute for Research, Madison, WI 53715); Page CD ( Department of Biostatistics and Medical Informatics, University of Wisconsin, Madison, WI 53792); Murphy WL ( Department of Biomedical Engineering, University of Wisconsin, Madison, WI 53706); Thomson JA ( Regenerative Biology, Morgridge Institute for Research, Madison, WI 53715); |
| 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. |
| ISSN |
00278424 |
| e-ISSN |
10916490 |
| Journal |
Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number |
40 |
| Volume Number |
112 |
| Language |
English |
| Publisher |
National Academy of Sciences |
| Publisher Date |
2015-10-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Cell Differentiation Embryonic Stem Cells Cytology Neural Stem Cells Pluripotent Stem Cells Brain Growth & Development Metabolism Cell Communication Drug Effects Genetics Cells, Cultured Culture Media, Serum-Free Pharmacology Endothelial Cells Gene Expression Regulation, Developmental Gene Ontology Hydrogels Macrophages Mesenchymal Stromal Cells Microglia Models, Biological Neurogenesis Polyethylene Glycols Support Vector Machines Tissue Engineering Xenobiotics Classification Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Multidisciplinary |
