A Method for Human Teratogen Detection by Geometrically Confined Cell Differentiation and Migration

Overview

Journal Sci Rep

Specialty Science

Date 2015 May 13

PMID 25966467

Citations 16

Authors

Jiangwa Xing

Yi-Chin Toh

Shuoyu Xu

Hanry Yu

Affiliations

Soon will be listed here.

Abstract

Unintended exposure to teratogenic compounds can lead to various birth defects; however current animal-based testing is limited by time, cost and high inter-species variability. Here, we developed a human-relevant in vitro model, which recapitulated two cellular events characteristic of embryogenesis, to identify potentially teratogenic compounds. We spatially directed mesoendoderm differentiation, epithelial-mesenchymal transition and the ensuing cell migration in micropatterned human pluripotent stem cell (hPSC) colonies to collectively form an annular mesoendoderm pattern. Teratogens could disrupt the two cellular processes to alter the morphology of the mesoendoderm pattern. Image processing and statistical algorithms were developed to quantify and classify the compounds' teratogenic potential. We not only could measure dose-dependent effects but also correctly classify species-specific drug (Thalidomide) and false negative drug (D-penicillamine) in the conventional mouse embryonic stem cell test. This model offers a scalable screening platform to mitigate the risks of teratogen exposures in human.

Citing Articles

An explainable map of human gastruloid morphospace reveals gastrulation failure modes and predicts teratogens.

Rufo J, Qiu C, Han D, Baxter N, Daley G, Wilson M bioRxiv. 2024; .

PMID: 39386623 PMC: 11463602. DOI: 10.1101/2024.09.20.614192.

Developmental Toxicity Studies: The Path towards Humanized 3D Stem Cell-Based Models.

A Branco M, Nunes T, Cabral J, Diogo M Int J Mol Sci. 2023; 24(5).

PMID: 36902285 PMC: 10002991. DOI: 10.3390/ijms24054857.

Pluripotent stem cell assays: Modalities and applications for predictive developmental toxicity.

Piersma A, Baker N, Daston G, Flick B, Fujiwara M, Knudsen T Curr Res Toxicol. 2022; 3:100074.

PMID: 35633891 PMC: 9130094. DOI: 10.1016/j.crtox.2022.100074.

Biomedical and societal impacts of in vitro embryo models of mammalian development.

Moris N, Alev C, Pera M, Martinez Arias A Stem Cell Reports. 2021; 16(5):1021-1030.

PMID: 33979591 PMC: 8185435. DOI: 10.1016/j.stemcr.2021.03.023.

Thalidomide affects limb formation and multiple myeloma related genes in human induced pluripotent stem cells and their mesoderm differentiation.

Shimizu M, Tachikawa S, Saitoh N, Nakazono K, Yu-Jung L, Suga M Biochem Biophys Rep. 2021; 26:100978.

PMID: 33763605 PMC: 7973312. DOI: 10.1016/j.bbrep.2021.100978.

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