{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T05:39:02Z","timestamp":1791005942927,"version":"4.1.0"},"reference-count":58,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2019,12,4]],"date-time":"2019-12-04T00:00:00Z","timestamp":1575417600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R01EY005665"],"award-info":[{"award-number":["R01EY005665"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["5T32EY007145-20"],"award-info":[{"award-number":["5T32EY007145-20"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["P30EY003790"],"award-info":[{"award-number":["P30EY003790"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["2U42 OD011158"],"award-info":[{"award-number":["2U42 OD011158"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>Cell\u2013cell communication plays a fundamental role in mediating corneal wound healing following injury or infection. Depending on the severity of the wound, regeneration of the cornea and the propensity for scar development are influenced by the acute resolution of the pro-fibrotic response mediated by closure of the wound via cellular and tissue contraction. Damage of the corneal epithelium, basement membrane, and anterior stroma following a superficial keratectomy is known to lead to significant provisional matrix deposition, including secretion of fibronectin and thrombospondin-1, as well as development of a corneal scar. In addition, corneal wounding has previously been shown to promote release of extracellular vesicles from the corneal epithelium, which, in addition to soluble factors, may play a role in promoting tissue regeneration. In this study, we report the development and characterization of a co-culture system of human corneal epithelial cells and corneal stromal fibroblasts cultured for 4 weeks to allow extracellular matrix deposition and tissue maturation. The secretion of provisional matrix components, as well as small and large extracellular vesicles, was apparent within the constructs, suggesting cell\u2013cell communication between epithelial and stromal cell populations. Laminin-1\u03b2 was highly expressed by the corneal epithelial layer with the presence of notable patches of basement membrane identified by transmission electron microscopy. Interestingly, we identified expression of collagen type III, fibronectin, and thrombospondin-1 along the epithelial\u2013stromal interface similar to observations seen in vivo following a keratectomy, as well as expression of the myofibroblast marker, \u03b1-smooth muscle actin, within the stroma. Our results suggest that this corneal epithelial\u2013stromal model may be useful in the study of the biochemical phenomena that occur during corneal wound healing.<\/jats:p>","DOI":"10.3390\/bioengineering6040110","type":"journal-article","created":{"date-parts":[[2019,12,5]],"date-time":"2019-12-05T03:16:36Z","timestamp":1575515796000},"page":"110","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Corneal Epithelial\u2013Stromal Fibroblast Constructs to Study Cell\u2013Cell Communication in Vitro"],"prefix":"10.3390","volume":"6","author":[{"given":"Tina B.","family":"McKay","sequence":"first","affiliation":[{"name":"Schepens Eye Research Institute\/Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8761-3824","authenticated-orcid":false,"given":"Dimitrios","family":"Karamichos","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology\/Dean McGee Eye Institute, University of Oklahoma Health Science Center, Oklahoma City, OK 73104, USA"},{"name":"Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey E. K.","family":"Hutcheon","sequence":"additional","affiliation":[{"name":"Schepens Eye Research Institute\/Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqing","family":"Guo","sequence":"additional","affiliation":[{"name":"Schepens Eye Research Institute\/Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James D.","family":"Zieske","sequence":"additional","affiliation":[{"name":"Schepens Eye Research Institute\/Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,4]]},"reference":[{"key":"ref_1","first-page":"214","article-title":"Corneal blindness: A global perspective","volume":"79","author":"Whitcher","year":"2001","journal-title":"Bull. 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