{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T01:29:23Z","timestamp":1791336563786,"version":"4.3.1"},"reference-count":80,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2023,7,15]],"date-time":"2023-07-15T00:00:00Z","timestamp":1689379200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Awards \u201cLombardia \u00e8 Ricerca 2018\u201d","award":["2007-13-Tecnopolo"],"award-info":[{"award-number":["2007-13-Tecnopolo"]}]},{"name":"\u201cLouis Jeantet Award 2020\u201d","award":["2007-13-Tecnopolo"],"award-info":[{"award-number":["2007-13-Tecnopolo"]}]},{"name":"Holostem Terapie Avanzate s.r.l.","award":["2007-13-Tecnopolo"],"award-info":[{"award-number":["2007-13-Tecnopolo"]}]},{"name":"Regione Emilia-Romagna","award":["2007-13-Tecnopolo"],"award-info":[{"award-number":["2007-13-Tecnopolo"]}]},{"name":"POR-FESR","award":["2007-13-Tecnopolo"],"award-info":[{"award-number":["2007-13-Tecnopolo"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Total bilateral Limbal Stem Cell Deficiency is a pathologic condition of the ocular surface due to the loss of corneal stem cells. Cultivated oral mucosa epithelial transplantation (COMET) is the only autologous successful treatment for this pathology in clinical application, although abnormal peripheric corneal vascularization often occurs. Properly characterizing the regenerated ocular surface is needed for a reliable follow-up. So far, the univocal identification of transplanted oral mucosa has been challenging. Previously proposed markers were shown to be co-expressed by different ocular surface epithelia in a homeostatic or perturbated environment. In this study, we compared the transcriptome profile of human oral mucosa, limbal and conjunctival cultured holoclones, identifying Paired Like Homeodomain 2 (PITX2) as a new marker that univocally distinguishes the transplanted oral tissue from the other epithelia. We validated PITX2 at RNA and protein levels to investigate 10-year follow-up corneal samples derived from a COMET-treated aniridic patient. Moreover, we found novel angiogenesis-related factors that were differentially expressed in the three epithelia and instrumental in explaining the neovascularization in COMET-treated patients. These results will support the follow-up analysis of patients transplanted with oral mucosa and provide new tools to understand the regeneration mechanism of transplanted corneas.<\/jats:p>","DOI":"10.3390\/ijms241411522","type":"journal-article","created":{"date-parts":[[2023,7,17]],"date-time":"2023-07-17T00:35:04Z","timestamp":1689554104000},"page":"11522","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Comparison between Cultivated Oral Mucosa and Ocular Surface Epithelia for COMET Patients Follow-Up"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9590-7630","authenticated-orcid":false,"given":"Eustachio","family":"Attico","sequence":"first","affiliation":[{"name":"Centre for Regenerative Medicine \u201cStefano Ferrari\u201d, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3130-7131","authenticated-orcid":false,"given":"Giulia","family":"Galaverni","sequence":"additional","affiliation":[{"name":"Centre for Regenerative Medicine \u201cStefano Ferrari\u201d, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Torello","sequence":"additional","affiliation":[{"name":"Centre for Regenerative Medicine \u201cStefano Ferrari\u201d, University of Modena and Reggio Emilia, 41125 Modena, Italy"},{"name":"Holostem Terapie Avanzate s.r.l., 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6110-5944","authenticated-orcid":false,"given":"Elisa","family":"Bianchi","sequence":"additional","affiliation":[{"name":"Centre for Regenerative Medicine \u201cStefano Ferrari\u201d, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna","family":"Bonacorsi","sequence":"additional","affiliation":[{"name":"Centre for Regenerative Medicine \u201cStefano Ferrari\u201d, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena","family":"Losi","sequence":"additional","affiliation":[{"name":"Unit of Pathology, Department of Life Sciences, University of Modena and Reggio Emilia, 41124 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0660-6110","authenticated-orcid":false,"given":"Rossella","family":"Manfredini","sequence":"additional","affiliation":[{"name":"Centre for Regenerative Medicine \u201cStefano Ferrari\u201d, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8974-991X","authenticated-orcid":false,"given":"Alessandro","family":"Lambiase","sequence":"additional","affiliation":[{"name":"Department of Sense Organs, Sapienza University of Rome, 00169 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Rama","sequence":"additional","affiliation":[{"name":"SC Ophathalmology, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graziella","family":"Pellegrini","sequence":"additional","affiliation":[{"name":"Centre for Regenerative Medicine \u201cStefano Ferrari\u201d, University of Modena and Reggio Emilia, 41125 Modena, Italy"},{"name":"Holostem Terapie Avanzate s.r.l., 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,15]]},"reference":[{"key":"ref_1","first-page":"169","article-title":"Stem cells and ocular regeneration","volume":"Volume 2","author":"Chiavelli","year":"2019","journal-title":"Encyclopedia of Tissue Engineering and Regenerative Medicine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5","DOI":"10.4103\/0974-9233.106381","article-title":"Presentation, Diagnosis and Management of Limbal Stem Cell Deficiency","volume":"20","author":"Sejpal","year":"2013","journal-title":"Middle East Afr. J. Ophthalmol."},{"key":"ref_3","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_4","doi-asserted-by":"crossref","first-page":"658","DOI":"10.3389\/fmed.2023.1125892","article-title":"Education for the translation of Advanced Therapy Medicinal Products","volume":"10","author":"Adamo","year":"2023","journal-title":"Front. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1002\/sctm.17-0003","article-title":"Navigating Market Authorization: The Path Holoclar Took to Become the First Stem Cell Product Approved in the European Union","volume":"7","author":"Pellegrini","year":"2018","journal-title":"Stem Cells Transl. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1007\/s40472-018-0202-0","article-title":"Approaches for Effective Clinical Application of Stem Cell Transplantation","volume":"5","author":"Attico","year":"2018","journal-title":"Curr. Transplant. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1097\/ICU.0000000000000385","article-title":"Conjunctival-limbal autograft","volume":"28","author":"Daya","year":"2017","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_8","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":"Kenyon","year":"1989","journal-title":"Ophthalmology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1016\/S0140-6736(96)11188-0","article-title":"Long-term restoration of damaged corneal surfaces with autologous cultivated corneal epithelium","volume":"349","author":"Pellegrini","year":"1997","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1136\/bjophthalmol-2011-301164","article-title":"Simple limbal epithelial transplantation (SLET): A novel surgical technique for the treatment of unilateral limbal stem cell deficiency","volume":"96","author":"Sangwan","year":"2012","journal-title":"Br. J. Ophthalmol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"652214","DOI":"10.3389\/fbioe.2021.652214","article-title":"Regenerative Medicine of Epithelia: Lessons from the Past and Future Goals","volume":"9","author":"Maurizi","year":"2021","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1056\/NEJMoa0905955","article-title":"Limbal Stem-Cell Therapy and Long-Term Corneal Regeneration","volume":"363","author":"Rama","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"553","DOI":"10.2217\/rme.13.43","article-title":"Biological parameters determining the clinical outcome of autologous cultures of limbal stem cells","volume":"8","author":"Pellegrini","year":"2013","journal-title":"Regen. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1136\/bjo.2003.038497","article-title":"Transplantation of cultivated autologous oral mucosal epithelial cells in patients with severe ocular surface disorders","volume":"88","author":"Nakamura","year":"2004","journal-title":"Br. J. Ophthalmol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s40135-020-00263-9","article-title":"Clinical Studies of COMET for Total LSCD: A Review of the Methods and Molecular Markers for Follow-Up Characterizations","volume":"9","author":"Attico","year":"2021","journal-title":"Curr. Ophthalmol. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1056\/NEJMp048199","article-title":"Changing the Cell Source in Cell Therapy?","volume":"351","author":"Pellegrini","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Soma, T., Hayashi, R., Sugiyama, H., Tsujikawa, M., Kanayama, S., Oie, Y., and Nishida, K. (2014). Maintenance and Distribution of Epithelial Stem\/Progenitor Cells after Corneal Reconstruction Using Oral Mucosal Epithelial Cell Sheets. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0110987"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1038\/mt.2014.69","article-title":"Evidence of the survival of ectopically transplanted oral mucosal epithelial stem cells after repeated wounding of cornea","volume":"22","author":"Sugiyama","year":"2014","journal-title":"Mol. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Zhang, X., Yin, M., and Zhang, L.J. (2019). Keratin 6, 16 and 17-Critical Barrier Alarmin Molecules in Skin Wounds and Psoriasis. Cells, 8.","DOI":"10.3390\/cells8080807"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Attico, E., Galaverni, G., Bianchi, E., Losi, L., Manfredini, R., Lambiase, A., Rama, P., and Pellegrini, G. (2022). SOX2 Is a Univocal Marker for Human Oral Mucosa Epithelium Useful in Post-COMET Patient Characterization. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23105785"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Kalabusheva, E.P., Shtompel, A.S., Rippa, A.L., Ulianov, S.V., Razin, S.V., and Vorotelyak, E.A. (2023). A Kaleidoscope of Keratin Gene Expression and the Mosaic of Its Regulatory Mechanisms. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24065603"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1056\/NEJMoa040455","article-title":"Corneal reconstruction with tissue-engineered cell sheets composed of autologous oral mucosal epithelium","volume":"351","author":"Nishida","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2302","DOI":"10.1073\/pnas.84.8.2302","article-title":"Three clonal types of keratinocyte with different capacities for multiplication","volume":"84","author":"Barrandon","year":"1987","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/bs.mcb.2022.02.009","article-title":"Clonal analysis of human clonogenic keratinocytes","volume":"170","author":"Enzo","year":"2022","journal-title":"Methods Cell Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/s10585-013-9620-7","article-title":"PITX2 and non-canonical Wnt pathway interaction in metastatic prostate cancer","volume":"31","author":"Vela","year":"2013","journal-title":"Clin. Exp. Metastasis"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.diff.2017.11.003","article-title":"Directed differentiation of periocular mesenchyme from human embryonic stem cells","volume":"99","author":"Lovatt","year":"2018","journal-title":"Differentiation"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Yam, G.H.-F., Seah, X., Yusoff, N.Z.B.M., Setiawan, M., Wahlig, S., Htoon, H.M., Peh, G.S.L., Kocaba, V., and Mehta, J.S. (2019). Characterization of Human Transition Zone Reveals a Putative Progenitor-Enriched Niche of Corneal Endothelium. Cells, 8.","DOI":"10.3390\/cells8101244"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5098","DOI":"10.1038\/onc.2017.132","article-title":"Tumor-secreted anterior gradient-2 binds to VEGF and FGF2 and enhances their activities by promoting their homodimerization","volume":"36","author":"Guo","year":"2017","journal-title":"Oncogene"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2856","DOI":"10.1111\/febs.14155","article-title":"Anterior gradient 2 is induced in cutaneous wound and promotes wound healing through its adhesion domain","volume":"284","author":"Zhu","year":"2017","journal-title":"FEBS J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3398","DOI":"10.1182\/blood-2009-01-197095","article-title":"\u03b1B-crystallin regulation of angiogenesis by modulation of VEGF","volume":"115","author":"Kase","year":"2010","journal-title":"Blood"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1016\/j.ajpath.2012.12.020","article-title":"Targeting the IRE1\u03b1\/XBP1 and ATF6 arms of the unfolded protein response enhances VEGF blockade to prevent retinal and choroidal neovascularization","volume":"182","author":"Liu","year":"2013","journal-title":"Am. J. Pathol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3700","DOI":"10.7150\/thno.19712","article-title":"Epiregulin promotes lung metastasis of salivary adenoid cystic carcinoma","volume":"7","author":"Yang","year":"2017","journal-title":"Theranostics"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"20833","DOI":"10.1074\/jbc.M412653200","article-title":"Metastasis-associated protein S100A4 induces angiogenesis through interaction with annexin II and accelerated plasmin formation","volume":"280","author":"Semov","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4685","DOI":"10.1038\/sj.onc.1204636","article-title":"The metastasis-associated Mts1(S100A4) protein could act as an angiogenic factor","volume":"20","author":"Ambartsumian","year":"2001","journal-title":"Oncogene"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5703","DOI":"10.1158\/0008-5472.CAN-04-4012","article-title":"Antibody against Junctional Adhesion Molecule-C Inhibits Angiogenesis and Tumor Growth","volume":"65","author":"Lamagna","year":"2005","journal-title":"Cancer Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1159\/000322804","article-title":"Inhibitory Effect of Canstatin in Alkali Burn-Induced Corneal Neovascularization","volume":"46","author":"Wang","year":"2011","journal-title":"Ophthalmic Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.jphs.2018.12.001","article-title":"A current perspective of canstatin, a fragment of type IV collagen alpha 2 chain","volume":"139","author":"Okada","year":"2019","journal-title":"J. Pharmacol. Sci."},{"key":"ref_38","first-page":"2905","article-title":"The Inflammatory Milieu Associated with Conjunctivalized Cornea and Its Alteration with IL-1 RA Gene Therapy","volume":"43","author":"Moore","year":"2002","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_39","first-page":"56","article-title":"Corneal neovascularization suppressed by TIMP2 released from human amniotic membranes","volume":"21","author":"Ma","year":"2005","journal-title":"Yan Ke Xue Bao Eye Sci. Yan Ke Xue Bao Bian Ji Bu"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"108363","DOI":"10.1016\/j.exer.2020.108363","article-title":"Corneal neovascularization","volume":"202","author":"Nicholas","year":"2021","journal-title":"Exp. Eye Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1167\/iovs.05-1305","article-title":"Unique distribution of thrombospondin-1 in human ocular surface epithelium","volume":"47","author":"Sekiyama","year":"2006","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1136\/bjophthalmol-2015-307901","article-title":"Angiopoietin 2 expression in the cornea and its control of corneal neovascularisation","volume":"100","author":"Ferrari","year":"2016","journal-title":"Br. J. Ophthalmol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Zakaria, N., Van Grasdorff, S., Wouters, K., Rozema, J., Koppen, C., Lion, E., Cools, N., Berneman, Z., and Tassignon, M.-J. (2012). Human Tears Reveal Insights into Corneal Neovascularization. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0036451"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"5615","DOI":"10.1167\/iovs.11-9293","article-title":"Expression of angiogenesis-related factors in human corneas after cultivated oral mucosal epithelial transplantation","volume":"53","author":"Chen","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1016\/j.exer.2007.08.011","article-title":"Analysis of angiogenesis induced by cultured corneal and oral mucosal epithelial cell sheets in vitro","volume":"85","author":"Kanayama","year":"2007","journal-title":"Exp. Eye Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"644","DOI":"10.4103\/0301-4738.109517","article-title":"Oral epithelial cells transplanted on to corneal surface tend to adapt to the ocular phenotype","volume":"62","author":"Gaddipati","year":"2014","journal-title":"Indian J. Ophthalmol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1097\/ICO.0000000000001409","article-title":"Prospective Clinical Trial of Corneal Reconstruction with Biomaterial-Free Cultured Oral Mucosal Epithelial Cell Sheets","volume":"37","author":"Kim","year":"2018","journal-title":"Cornea"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1136\/bjo.85.5.604","article-title":"The long term outcome of limbal allografts: The search for surviving cells","volume":"85","author":"Henderson","year":"2001","journal-title":"Br. J. Ophthalmol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/S0002-9394(14)72164-6","article-title":"Use of DNA polymorphisms and the polymerase chain reaction to examine the survival of a human limbal stem cell allograft","volume":"120","author":"Williams","year":"1995","journal-title":"Am. J. Ophthalmol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1016\/j.bbrc.2019.04.202","article-title":"Oral keratinocyte-derived exosomes regulate proliferation of fibroblasts and epithelial cells","volume":"514","author":"Sjoqvist","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1565264","DOI":"10.1080\/20013078.2019.1565264","article-title":"Exosomes derived from clinical-grade oral mucosal epithelial cell sheets promote wound healing","volume":"8","author":"Ishikawa","year":"2019","journal-title":"J. Extracell. Vesicles"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1369\/0022155420980071","article-title":"Subconjunctival Injection of Transdifferentiated Oral Mucosal Epithelial Cells for Limbal Stem Cell Deficiency in Rats","volume":"69","author":"Xiao","year":"2021","journal-title":"J. Histochem. Cytochem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.stemcr.2013.11.001","article-title":"Long-term stability and safety of transgenic cultured epidermal stem cells in gene therapy of junctional epidermolysis bullosa","volume":"2","author":"Carulli","year":"2014","journal-title":"Stem Cell Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/nm.3028","article-title":"The meaning, the sense and the significance: Translating the science of mesenchymal stem cells into medicine","volume":"19","author":"Bianco","year":"2013","journal-title":"Nat. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1097\/00007890-199009000-00019","article-title":"Evidence that human oral epithelium reconstituted in vitro and transplanted onto patients with defects in the oral mucosa retains properties of the original donor site","volume":"50","author":"Albanese","year":"1990","journal-title":"Transplantation"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/j.ajo.2006.06.004","article-title":"Ocular Surface Reconstruction with Combination of Cultivated Autologous Oral Mucosal Epithelial Transplantation and Penetrating Keratoplasty","volume":"142","author":"Inatomi","year":"2006","journal-title":"Am. J. Ophthalmol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1016\/j.ophtha.2006.09.034","article-title":"Phenotypic Investigation of Human Eyes with Transplanted Autologous Cultivated Oral Mucosal Epithelial Sheets for Severe Ocular Surface Diseases","volume":"114","author":"Nakamura","year":"2007","journal-title":"Ophthalmology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"4660","DOI":"10.1167\/iovs.09-3377","article-title":"Persistence of transplanted oral mucosal epithelial cells in human cornea","volume":"50","author":"Chen","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1007\/s00418-008-0435-6","article-title":"The human keratins: Biology and pathology","volume":"129","author":"Moll","year":"2008","journal-title":"Histochem. Cell Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.jtos.2019.11.002","article-title":"Early phenotypic features of aniridia-associated keratopathy and association with PAX6 coding mutations","volume":"18","author":"Lagali","year":"2020","journal-title":"Ocul. Surf."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.jtos.2021.09.001","article-title":"Pathophysiology of aniridia-associated keratopathy: Developmental aspects and unanswered questions","volume":"22","author":"Latta","year":"2021","journal-title":"Ocul. Surf."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1002\/dvdy.24165","article-title":"The homeodomain transcription factor PITX2 is required for specifying correct cell fates and establishing angiogenic privilege in the developing cornea","volume":"243","author":"Gage","year":"2014","journal-title":"Dev. Dyn."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"dev186023","DOI":"10.1242\/dev.186023","article-title":"Pitx2-Sox2-Lef-1 interactions specify progenitor oral\/dental epithelial cell signaling centers","volume":"147","author":"Yu","year":"2020","journal-title":"Development"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1242\/dev.127.5.1081","article-title":"Mesendoderm and left-right brain, heart and gut development are differentially regulated by pitx2 isoforms","volume":"127","author":"Essner","year":"2000","journal-title":"Development"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1242\/dev.129.2.329","article-title":"Pitx2 is required at multiple stages of pituitary organogenesis: Pituitary primordium formation and cell specification","volume":"129","author":"Suh","year":"2002","journal-title":"Development"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"6375","DOI":"10.1242\/dev.00849","article-title":"Genetic dissection of Pitx2 in craniofacial development uncovers new functions in branchial arch morphogenesis, late aspects of tooth morphogenesis and cell migration","volume":"130","author":"Liu","year":"2003","journal-title":"Development"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Sofyanti, E., Boel, T., Pratamawati, T., and Auerkari, E.I. (2017, January 7\u20139). Prediction of Regulatory Networks of PITX2 Gene Expression in Mandibular Asymmetry Related to Oral Muscle Function. Proceedings of the International Dental Conference of Sumatera Utara 2017 (IDCSU 2017), Medan, Indonesia.","DOI":"10.2991\/idcsu-17.2018.24"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/S1050-1738(03)00039-2","article-title":"The role of Pitx2 during Cardiac Development","volume":"13","author":"Franco","year":"2003","journal-title":"Trends Cardiovasc. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.ydbio.2003.10.035","article-title":"PITX2 is required for normal development of neurons in the mouse subthalamic nucleus and midbrain","volume":"267","author":"Martin","year":"2004","journal-title":"Dev. Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1167\/iovs.15-18103","article-title":"AP-2\u03b2 is a downstream effector of PITX2 required to specify endothelium and establish angiogenic privilege during corneal development","volume":"57","author":"Chen","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_71","first-page":"2456","article-title":"Phenotypic Variability and Asymmetry of Rieger Syndrome Associated with PITX2 Mutations","volume":"41","author":"Perveen","year":"2000","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2567","DOI":"10.1002\/ijc.27930","article-title":"PITX2: A promising predictive biomarker of patients\u2019 prognosis and chemoradioresistance in esophageal squamous cell carcinoma","volume":"132","author":"Zhang","year":"2013","journal-title":"Int. J. Cancer"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e385","DOI":"10.1016\/j.clcc.2018.02.008","article-title":"Significance of PITX2 Promoter Methylation in Colorectal Carcinoma Prognosis","volume":"17","author":"Semaan","year":"2018","journal-title":"Clin. Color. Cancer"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Fung, F.K.C., Chan, D.W., Liu, V.W.S., Leung, T.H.Y., Cheung, A.N.Y., and Ngan, H.Y.S. (2012). Increased expression of PITX2 transcription factor contributes to ovarian cancer progression. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0037076"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.4161\/cc.9.7.11126","article-title":"Pituitary homeobox 2 (PITX2) promotes thyroid carcinogenesis by activation of cyclin D2","volume":"9","author":"Huang","year":"2010","journal-title":"Cell Cycle"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"25001","DOI":"10.1074\/jbc.M201737200","article-title":"Differential regulation of gene expression by PITX2 isoforms","volume":"277","author":"Cox","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Lamba, P., Hjalt, T.A., and Bernard, D.J. (2008). Novel forms of Paired-like homeodomain transcription factor 2 (PITX2): Generation by alternative translation initiation and mRNA splicing. BMC Mol. Biol., 9.","DOI":"10.1186\/1471-2199-9-31"},{"key":"ref_78","first-page":"1","article-title":"The cell as a tool to understand and repair urethra","volume":"Volume 1","author":"Hofer","year":"2022","journal-title":"Scientific Advances in Reconstructive Urology and Tissue Engineering"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.1007\/s00345-019-02864-x","article-title":"Preclinical study for treatment of hypospadias by advanced therapy medicinal products","volume":"38","author":"Sceberras","year":"2020","journal-title":"World J. Urol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1093\/bioinformatics\/btt703","article-title":"Causal analysis approaches in ingenuity pathway analysis","volume":"30","author":"Green","year":"2014","journal-title":"Bioinformatics"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/14\/11522\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:12:47Z","timestamp":1760127167000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/14\/11522"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,15]]},"references-count":80,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["ijms241411522"],"URL":"https:\/\/doi.org\/10.3390\/ijms241411522","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,15]]}}}