{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T11:28:51Z","timestamp":1790508531281,"version":"4.1.0"},"reference-count":56,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T00:00:00Z","timestamp":1684368000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Promotion and Mutual Aid Corporation for Private Schools of Japan"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The first product in the world for ex vivo cultivated oral mucosal epithelial cell transplantation (COMET) to treat limbal stem cell deficiency (LSCD), named Ocural\u00ae, was launched in June 2021 in Japan. COMET was performed on two patients, including the first case in the post-marketing phase of Ocural\u00ae. Pathological and immunohistochemical examinations were also carried out using specimens obtained before and after COMET and the spare cell sheet. In case 1, the ocular surface remained free from epithelial defects for approximately six months. In case 2, although defect of the cornea-like epithelia was observed after COMET for one month, it was resolved after the insertion of lacrimal punctal plugs. In case 1, adjuvant treatment was interrupted due to an accident during the second month after COMET, resulting in conjunctival ingrowth and corneal opacity. Eventually, a lamellar keratoplasty was required at six months after COMET. Immunohistochemistry revealed the presence of markers for stem cells (p63, p75), proliferation (Ki-67), and differentiation (Keratin-3, -4, and -13) in both the cornea-like tissue after COMET and a cultivated oral mucosal epithelial cell sheet. In conclusion, Ocural\u00ae can be accomplished without major complications, and the stem cells derived from oral mucosa might be successfully engrafted.<\/jats:p>","DOI":"10.3390\/ijms24108926","type":"journal-article","created":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T08:09:44Z","timestamp":1684397384000},"page":"8926","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Early Clinical Outcomes of the First Commercialized Human Autologous Ex Vivo Cultivated Oral Mucosal Epithelial Cell Transplantation for Limbal Stem Cell Deficiency: Two Case Reports and Literature Review"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4260-6687","authenticated-orcid":false,"given":"Hiroshi","family":"Toshida","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Juntendo University Shizuoka Hospital, Shizuoka 410-2211, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoto","family":"Kasahara","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Juntendo University Shizuoka Hospital, Shizuoka 410-2211, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masamichi","family":"Kiriyama","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Juntendo University Shizuoka Hospital, Shizuoka 410-2211, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuma","family":"Iwasaki","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Juntendo University Shizuoka Hospital, Shizuoka 410-2211, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jobu","family":"Sugita","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Juntendo University Shizuoka Hospital, Shizuoka 410-2211, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohei","family":"Ichikawa","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Juntendo University Shizuoka Hospital, Shizuoka 410-2211, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiko","family":"Ohta","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Juntendo University Shizuoka Hospital, Shizuoka 410-2211, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsumi","family":"Miyahara","sequence":"additional","affiliation":[{"name":"Laboratory of Morphology and Image Analysis, Biomedical Research Core Facilities, Juntendo University Graduate School of Medicine, Tokyo 113-0033, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1097\/ICO.0000000000001820","article-title":"Global Consensus on Definition, Classification, Diagnosis, and Staging of Limbal Stem Cell Deficiency","volume":"38","author":"Deng","year":"2019","journal-title":"Cornea"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1097\/ICO.0000000000002358","article-title":"Global Consensus on the Management of Limbal Stem Cell Deficiency","volume":"39","author":"Deng","year":"2020","journal-title":"Cornea"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/S0161-6420(89)32833-8","article-title":"Limbal Autograft Transplantation for Ocular Surface Disorders","volume":"96","author":"Keivyon","year":"1989","journal-title":"Ophthalmology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1097\/00003226-199409000-00003","article-title":"Human Allograft Limbal Transplantation for Corneal Surface Reconstruction","volume":"13","author":"Tsai","year":"1994","journal-title":"Cornea"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1097\/00003226-199901000-00009","article-title":"Keratolimbal allograft: Recommendations for tissue procurement and preparation by eye banks, and standard surgical technique","volume":"18","author":"Croasdale","year":"1999","journal-title":"Cornea"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1056\/NEJM199906033402201","article-title":"Treatment of Severe Ocular-Surface Disorders with Corneal Epithelial Stem-Cell Transplantation","volume":"340","author":"Tsubota","year":"1999","journal-title":"N. 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