{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T22:28:58Z","timestamp":1775255338706,"version":"3.50.1"},"reference-count":48,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2018,10,22]],"date-time":"2018-10-22T00:00:00Z","timestamp":1540166400000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2018,10,16]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cleft palate (CP) is a common birth defect, occurring in an estimated 1 in 1,000 births worldwide. The secondary palate is formed by paired palatal shelves, consisting of a mesenchymal core with an outer layer of epithelial cells that grow toward each other, attach, and fuse. One of the mechanisms that can cause CP is failure of fusion, that is, failure to remove the epithelial seam between the palatal shelves to allow the mesenchyme confluence. Epidermal growth factor (EGF) plays an important role in palate growth and differentiation, while it may impede fusion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We developed a 3D organotypic model using human mesenchymal and epithelial stem cells to mimic human embryonic palatal shelves, and tested the effects of human EGF (hEGF) on proliferation and fusion. Spheroids were generated from human umbilical\u2010derived mesenchymal stem cells (hMSCs) directed down an osteogenic lineage. Heterotypic spheroids, or organoids, were constructed by coating hMSC spheroids with extracellular matrix solution followed by a layer of human progenitor epithelial keratinocytes (hPEKs). Organoids were incubated in co\u2010culture medium with or without hEGF and assessed for cell proliferation and time to fusion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Osteogenic differentiation in hMSC spheroids was highest by Day 13. hEGF delayed fusion of organoids after 12 and 18\u2009hr of contact. hEGF increased proliferation in organoids at 4 ng\/ml, and proliferation was detected in hPEKs alone.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our results show that this model of human palatal fusion appropriately mimics the morphology of the developing human palate and responds to hEGF as expected.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bdr2.1394","type":"journal-article","created":{"date-parts":[[2018,10,22]],"date-time":"2018-10-22T14:22:07Z","timestamp":1540218127000},"page":"1322-1334","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Development of an organotypic stem cell model for the study of human embryonic palatal fusion"],"prefix":"10.1002","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0703-2967","authenticated-orcid":false,"given":"Cynthia J.","family":"Wolf","sequence":"first","affiliation":[{"name":"Toxicity Assessment Division, National Health and Environmental Effects Research Laboratories Office of Research and Development, US EPA Research Triangle Park North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David G.","family":"Belair","sequence":"additional","affiliation":[{"name":"Toxicity Assessment Division, National Health and Environmental Effects Research Laboratories Office of Research and Development, US EPA Research Triangle Park North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carrie M.","family":"Becker","sequence":"additional","affiliation":[{"name":"Oak Ridge Institute for Science and Education Oak Ridge Tennessee"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaberi P.","family":"Das","sequence":"additional","affiliation":[{"name":"Toxicity Assessment Division, National Health and Environmental Effects Research Laboratories Office of Research and Development, US EPA Research Triangle Park North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judith E.","family":"Schmid","sequence":"additional","affiliation":[{"name":"Toxicity Assessment Division, National Health and Environmental Effects Research Laboratories Office of Research and Development, US EPA Research Triangle Park North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara D.","family":"Abbott","sequence":"additional","affiliation":[{"name":"Toxicity Assessment Division, National Health and Environmental Effects Research Laboratories Office of Research and Development, US EPA Research Triangle Park North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,10,22]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdrb.20252"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.102.4.853"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420420604"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20133"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0041-008X(89)90096-3"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02628837"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9926(199808)58:2<30::AID-TERA4>3.0.CO;2-4"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2007.06.018"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2010.12.028"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0184155"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(84)90186-6"},{"issue":"3","key":"e_1_2_6_13_1","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1387\/ijdb.8292539","article-title":"The distribution of epidermal growth factor binding sites in the developing mouse palate","volume":"37","author":"Brunet C. 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