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Over the past decades, several alternative in vitro assays have been developed, but these often suffered from low predictability and the inability to provide a mechanistic understanding of developmental toxicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To identify embryotoxic compounds, we developed a human induced pluripotent stem cells (hiPSCs)\u2010based biomarker assay. The assay is based on the differentiation of hiPSCs into functional cardiomyocytes and hepatocytes. Proper stem cell differentiation is investigated by morphological profiling and assessment of time\u2010dependent expression patterns of cell\u2010specific biomarkers. In this system, a decrease in the expression of the biomarker genes and morphology disruption of the differentiated cells following compound treatment indicated teratogenicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The hiPSCs\u2010based biomarker assay was validated with 21 well\u2010established in vivo animal teratogenic and non\u2010teratogenic compounds during cardiomyocyte and hepatocyte differentiation. The in vivo teratogenic compounds (e.g., thalidomide and valproic acid) markedly disrupted morphology, functionality, and the expression pattern of the biomarker genes in either one or both cell types. Non\u2010teratogenic chemicals generally had no effect on the morphology of differentiated cells, nor on the expression of the biomarker genes. Compared to the in vivo classification, the assay achieved high accuracy (91%), sensitivity (91%), and specificity (90%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The assay, which we named ReproTracker\u00ae, is a state\u2010of\u2010the\u2010art in vitro method that can identify the teratogenicity potential of new pharmaceuticals and chemicals and signify the outcome of in vivo test systems.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bdr2.2001","type":"journal-article","created":{"date-parts":[[2022,3,15]],"date-time":"2022-03-15T01:34:20Z","timestamp":1647308060000},"page":"1210-1228","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["A novel human stem cell\u2010based biomarker assay for in vitro assessment of developmental toxicity"],"prefix":"10.1002","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5630-4159","authenticated-orcid":false,"given":"Amer","family":"Jamalpoor","sequence":"first","affiliation":[{"name":"Toxys B.V., Leiden Bio Science Park  Oegstgeest The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Hartvelt","sequence":"additional","affiliation":[{"name":"Toxys B.V., Leiden Bio Science Park  Oegstgeest The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myrto","family":"Dimopoulou","sequence":"additional","affiliation":[{"name":"Toxys B.V., Leiden Bio Science Park  Oegstgeest The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Zwetsloot","sequence":"additional","affiliation":[{"name":"Toxys B.V., Leiden Bio Science Park  Oegstgeest The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inger","family":"Brandsma","sequence":"additional","affiliation":[{"name":"Toxys B.V., Leiden Bio Science Park  Oegstgeest The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter I.","family":"Racz","sequence":"additional","affiliation":[{"name":"Toxys B.V., Leiden Bio Science Park  Oegstgeest The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torben","family":"Osterlund","sequence":"additional","affiliation":[{"name":"Toxys B.V., Leiden Bio Science Park  Oegstgeest The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giel","family":"Hendriks","sequence":"additional","affiliation":[{"name":"Toxys B.V., Leiden Bio Science Park  Oegstgeest The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,3,14]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"crossref","unstructured":"Abramavicius S. 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