In Vitro Micropatterned Human Pluripotent Stem Cell Test (µP-hPST) for Morphometric-Based Teratogen Screening

Abstract Exposure to teratogenic chemicals during pregnancy may cause severe birth defects. Due to high inter-species variation of drug responses as well as financial and ethical burdens, despite the widely use of in vivo animal tests, it’s crucial to develop highly predictive human pluripotent stem...

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Autores principales:	Jiangwa Xing, Yue Cao, Yang Yu, Huan Li, Ziwei Song, Hanry Yu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/94247d11941b4a47967d938b9b754452
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spelling	oai:doaj.org-article:94247d11941b4a47967d938b9b7544522021-12-02T12:32:46ZIn Vitro Micropatterned Human Pluripotent Stem Cell Test (µP-hPST) for Morphometric-Based Teratogen Screening10.1038/s41598-017-09178-12045-2322https://doaj.org/article/94247d11941b4a47967d938b9b7544522017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09178-1https://doaj.org/toc/2045-2322Abstract Exposure to teratogenic chemicals during pregnancy may cause severe birth defects. Due to high inter-species variation of drug responses as well as financial and ethical burdens, despite the widely use of in vivo animal tests, it’s crucial to develop highly predictive human pluripotent stem cell (hPSC)-based in vitro assays to identify potential teratogens. Previously we have shown that the morphological disruption of mesoendoderm patterns formed by geometrically-confined cell differentiation and migration using hPSCs could potentially serve as a sensitive morphological marker in teratogen detection. Here, a micropatterned human pluripotent stem cell test (µP-hPST) assay was developed using 30 pharmaceutical compounds. A simplified morphometric readout was developed to quantify the mesoendoderm pattern changes and a two-step classification rule was generated to identify teratogens. The optimized µP-hPST could classify the 30 compounds with 97% accuracy, 100% specificity and 93% sensitivity. Compared with metabolic biomarker-based hPSC assay by Stemina, the µP-hPST could successfully identify misclassified drugs Bosentan, Diphenylhydantoin and Lovastatin, and show a higher accuracy and sensitivity. This scalable µP-hPST may serve as either an independent assay or a complement assay for existing assays to reduce animal use, accelerate early discovery-phase drug screening and help general chemical screening of human teratogens.Jiangwa XingYue CaoYang YuHuan LiZiwei SongHanry YuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jiangwa Xing Yue Cao Yang Yu Huan Li Ziwei Song Hanry Yu In Vitro Micropatterned Human Pluripotent Stem Cell Test (µP-hPST) for Morphometric-Based Teratogen Screening
description	Abstract Exposure to teratogenic chemicals during pregnancy may cause severe birth defects. Due to high inter-species variation of drug responses as well as financial and ethical burdens, despite the widely use of in vivo animal tests, it’s crucial to develop highly predictive human pluripotent stem cell (hPSC)-based in vitro assays to identify potential teratogens. Previously we have shown that the morphological disruption of mesoendoderm patterns formed by geometrically-confined cell differentiation and migration using hPSCs could potentially serve as a sensitive morphological marker in teratogen detection. Here, a micropatterned human pluripotent stem cell test (µP-hPST) assay was developed using 30 pharmaceutical compounds. A simplified morphometric readout was developed to quantify the mesoendoderm pattern changes and a two-step classification rule was generated to identify teratogens. The optimized µP-hPST could classify the 30 compounds with 97% accuracy, 100% specificity and 93% sensitivity. Compared with metabolic biomarker-based hPSC assay by Stemina, the µP-hPST could successfully identify misclassified drugs Bosentan, Diphenylhydantoin and Lovastatin, and show a higher accuracy and sensitivity. This scalable µP-hPST may serve as either an independent assay or a complement assay for existing assays to reduce animal use, accelerate early discovery-phase drug screening and help general chemical screening of human teratogens.
format	article
author	Jiangwa Xing Yue Cao Yang Yu Huan Li Ziwei Song Hanry Yu
author_facet	Jiangwa Xing Yue Cao Yang Yu Huan Li Ziwei Song Hanry Yu
author_sort	Jiangwa Xing
title	In Vitro Micropatterned Human Pluripotent Stem Cell Test (µP-hPST) for Morphometric-Based Teratogen Screening
title_short	In Vitro Micropatterned Human Pluripotent Stem Cell Test (µP-hPST) for Morphometric-Based Teratogen Screening
title_full	In Vitro Micropatterned Human Pluripotent Stem Cell Test (µP-hPST) for Morphometric-Based Teratogen Screening
title_fullStr	In Vitro Micropatterned Human Pluripotent Stem Cell Test (µP-hPST) for Morphometric-Based Teratogen Screening
title_full_unstemmed	In Vitro Micropatterned Human Pluripotent Stem Cell Test (µP-hPST) for Morphometric-Based Teratogen Screening
title_sort	in vitro micropatterned human pluripotent stem cell test (µp-hpst) for morphometric-based teratogen screening
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/94247d11941b4a47967d938b9b754452
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In Vitro Micropatterned Human Pluripotent Stem Cell Test (µP-hPST) for Morphometric-Based Teratogen Screening

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