{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T04:01:21Z","timestamp":1792814481694,"version":"4.5.0"},"reference-count":57,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,2,6]],"date-time":"2018-02-06T00:00:00Z","timestamp":1517875200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["1U54HD090257\u201001"],"award-info":[{"award-number":["1U54HD090257\u201001"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Biomedical Materials Res"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Fetal cytotrophoblast invasion of maternal decidual vasculature is necessary to normal pregnancy. In preeclampsia, there is shallow invasion and abnormal remodeling of the uterine vasculature that lead to significant maternal and perinatal morbidity and mortality. The placental basement membrane (BM) proteins (e.g., laminin and collagen) has been implicated in the development of placenta while the level of laminin is significantly lower in preeclampsia. However, there are very limited studies, if any, on the effect of extracellular matrix (ECM) microenvironment on the invasion of cytotrophoblast. In this study, we hypothesized that placental BM proteins are required for effective cytotrophoblast invasion. Using proteomics, we found that more than 80% of ECM proteins in placental basal plate (pECM) were BM proteins. In addition to upregulating expressions of MMP2 (1.5\u2010fold) and MMP9 (6.3\u2010fold), pECM significantly increased the motility rates of cytotrophoblasts by 13\u2010fold (from 5.60\u2009\u00b1\u20090.95 to 75.5\u2009\u00b1\u200921.8 \u00b5m\/day) to achieve an effective invasion rate that was comparable to<jats:italic>in vivo<\/jats:italic>results. Treatments with PI3K inhibitors completely removed the pECM\u2010enhanced invasive phenotypes and genotypes of cytotrophoblasts, suggesting its dominant role in cytotrophoblast\u2010ECM interactions. Our results described, for the first time, the substantial effects of the ECM microenvironment on regulating cytotrophoblast invasion, an area that is less investigated but appear to be critical in the pathogenesis of preeclampsia. Moreover, the approach presented in this work that fabricates organ models with organ\u2010specific ECM can be an attractive option to screen and develop novel therapeutics and biomarkers not only in preeclampsia but also other diseases such as cancer metastasis. \u00a9 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1476\u20131487, 2018.<\/jats:p>","DOI":"10.1002\/jbm.a.36350","type":"journal-article","created":{"date-parts":[[2018,1,25]],"date-time":"2018-01-25T06:56:46Z","timestamp":1516863406000},"page":"1476-1487","source":"Crossref","is-referenced-by-count":54,"title":["Placental basement membrane proteins are required for effective cytotrophoblast invasion in a three\u2010dimensional bioprinted placenta model"],"prefix":"10.1002","volume":"106","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0366-8386","authenticated-orcid":false,"given":"Che\u2010Ying","family":"Kuo","sequence":"first","affiliation":[{"name":"Fischell Department of Bioengineering, University of Maryland, College Park Maryland 20740"},{"name":"Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Health System Washington District of Columbia 20010"},{"name":"Center for Engineering Complex Tissues University of Maryland College Park Maryland 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