期刊
EXPERIMENTAL BIOLOGY AND MEDICINE
卷 242, 期 17, 页码 1679-1689出版社
SAGE PUBLICATIONS LTD
DOI: 10.1177/1535370217715028
关键词
Biomaterial; development; neurotoxicology; matrix; organoid; screening
资金
- Environmental Protection Agency (STAR) [83573701]
- U.S. Department of Health and Human Services National Institutes of Health (National Center for Advancing Translational Sciences) [1UH2TR000506-01, 1UH3TR 000506-01U.S.]
- U.S. Department of Health and Human Services National Institutes of Health (National Heart, Lung, and Blood Institute) [R01HL093282-01A1]
- Canadian Institutes of Health Research Banting Postdoctoral Fellowship
The aim of the present study was to test sample reproducibility for model neural tissues formed on synthetic hydrogels. Human embryonic stem (ES) cell-derived precursor cells were cultured on synthetic poly(ethylene glycol) (PEG) hydrogels to promote differentiation and self-organization into model neural tissue constructs. Neural progenitor, vascular, and microglial precursor cells were combined on PEG hydrogels to mimic developmental timing, which produced multicomponent neural constructs with 3D neuronal and glial organization, organized vascular networks, and microglia with ramified morphologies. Spearman's rank correlation analysis of global gene expression profiles and a comparison of coefficient of variation for expressed genes demonstrated that replicate neural constructs were highly uniform to at least day 21 for samples from independent experiments. We also demonstrate that model neural tissues formed on PEG hydrogels using a simplified neural differentiation protocol correlated more strongly to invivo brain development than samples cultured on tissue culture polystyrene surfaces alone. These results provide a proof-of-concept demonstration that 3D cellular models that mimic aspects of human brain development can be produced from human pluripotent stem cells with high sample uniformity between experiments by using standard culture techniques, cryopreserved cell stocks, and a synthetic extracellular matrix.
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