{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:27:47Z","timestamp":1790188067617,"version":"4.1.0"},"reference-count":85,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,6,27]],"date-time":"2023-06-27T00:00:00Z","timestamp":1687824000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"EU COST CA18116"},{"name":"EU Horizon 2020 Arrest Blindness"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The limbus, the vascularized junction between the cornea and conjunctiva, is thought to function as a barrier against corneal neovascularization. However, the exact mechanisms regulating this remain unknown. In this study, the limbal epithelial stem cell (LESC) marker ABCB5 was used to investigate the role of LESCs in corneal neovascularization. In an ABCB5KO model, a mild but significant increase of limbal lymphatic and blood vascular network complexity was observed in developing mice (4 weeks) but not in adult mice. Conversely, when using a cornea suture model, the WT animals exhibited a mild but significant increase in the number of lymphatic vessel sprouts compared to the ABCB5KO, suggesting a contextual anti-lymphangiogenic effect of ABCB5 on the limbal vasculature during development, but a pro-lymphangiogenic effect under inflammatory challenge in adulthood. In addition, conditioned media from ABCB5-positive cultured human limbal epithelial cells (ABCB5+) stimulated human blood and lymphatic endothelial cell proliferation and migration. Finally, a proteomic analysis demonstrated ABCB5+ cells have a pro(lymph)angiogenic as well as an anti-inflammatory profile. These data suggest a novel dual, context-dependent role of ABCB5+ LESCs, inhibiting developmental but promoting inflammatory (lymph)angiogenesis in adulthood and exerting anti-inflammatory effects. These findings are of high clinical relevance in relation to LESC therapy against blindness.<\/jats:p>","DOI":"10.3390\/cells12131731","type":"journal-article","created":{"date-parts":[[2023,6,28]],"date-time":"2023-06-28T00:33:07Z","timestamp":1687912387000},"page":"1731","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["ABCB5+ Limbal Epithelial Stem Cells Inhibit Developmental but Promote Inflammatory (Lymph) Angiogenesis While Preventing Corneal Inflammation"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-3646-3823","authenticated-orcid":false,"given":"Berbang","family":"Meshko","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, University of Cologne, 50937 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3519-1359","authenticated-orcid":false,"given":"Thomas L. A.","family":"Volatier","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Cologne, 50937 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9713-1477","authenticated-orcid":false,"given":"Karina","family":"Hadrian","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Cologne, 50937 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuya","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Cologne, 50937 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhong","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Cologne, 50937 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0764-4645","authenticated-orcid":false,"given":"Mark Andreas","family":"Kluth","sequence":"additional","affiliation":[{"name":"TICEBA GmbH, Im Neuenheimer Feld 517, 69120 Heidelberg, Germany"},{"name":"RHEACELL GmbH & Co. KG, Im Neuenheimer Feld 517, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Ganss","sequence":"additional","affiliation":[{"name":"TICEBA GmbH, Im Neuenheimer Feld 517, 69120 Heidelberg, Germany"},{"name":"RHEACELL GmbH & Co. KG, Im Neuenheimer Feld 517, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1312-0488","authenticated-orcid":false,"given":"Markus H.","family":"Frank","sequence":"additional","affiliation":[{"name":"Transplant Research Program, Boston Children\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Harvard Skin Disease Research Center, Department of Dermatology, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA"},{"name":"School of Medical and Health Sciences, Edith Cowan University, Perth, WA 6027, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha Y.","family":"Frank","sequence":"additional","affiliation":[{"name":"Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA"},{"name":"Department of Medicine, VA Boston Healthcare System, Boston, MA 02132, USA"},{"name":"Division of Genetics, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce","family":"Ksander","sequence":"additional","affiliation":[{"name":"Massachusetts Eye & Ear Infirmary, Schepens Eye Research Institute, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1958-411X","authenticated-orcid":false,"given":"Claus","family":"Cursiefen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Cologne, 50937 Cologne, Germany"},{"name":"Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50937 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Notara","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Cologne, 50937 Cologne, Germany"},{"name":"Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50937 Cologne, Germany"},{"name":"Institute for Genome Stability in Ageing and Disease, CECAD Research Center, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"47156","DOI":"10.1074\/jbc.M308700200","article-title":"Regulation of progenitor cell fusion by ABCB5 P-glycoprotein, a novel human ATP-binding cassette transporter","volume":"278","author":"Frank","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/nature06489","article-title":"Identification of cells initiating human melanomas","volume":"451","author":"Schatton","year":"2008","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1038\/nature13426","article-title":"ABCB5 is a limbal stem cell gene required for corneal development and repair","volume":"511","author":"Ksander","year":"2014","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Vereb, Z., Albert, R., Poliska, S., Olstad, O.K., Akhtar, S., Moe, M.C., and Petrovski, G. (2013). Comparison of upstream regulators in human ex vivo cultured cornea limbal epithelial stem cells and differentiated corneal epithelial cells. BMC Genom., 14.","DOI":"10.1186\/1471-2164-14-900"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1167\/iovs.15-18343","article-title":"Short-Term Ultraviolet A Irradiation Leads to Dysfunction of the Limbal Niche Cells and an Antilymphangiogenic and Anti-inflammatory Micromilieu","volume":"57","author":"Notara","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/j.scr.2015.10.008","article-title":"Short-term uvb-irradiation leads to putative limbal stem cell damage and niche cell-mediated upregulation of macrophage recruiting cytokines","volume":"15","author":"Notara","year":"2015","journal-title":"Stem Cell Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.ophtha.2011.01.041","article-title":"Horizons in therapy for corneal angiogenesis limbal stem cell deficiency and corneal neovascularization","volume":"118","author":"Maddula","year":"2011","journal-title":"Ophthalmology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1080\/08820530902801478","article-title":"Limbal stem cell deficiency and corneal neovascularization","volume":"24","author":"Lim","year":"2009","journal-title":"Semin. Ophthalmol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"11405","DOI":"10.1073\/pnas.0506112103","article-title":"Nonvascular VEGF receptor 3 expression by corneal epithelium maintains avascularity and vision","volume":"103","author":"Cursiefen","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1136\/bjo.2006.107417","article-title":"Soluble vascular endothelial growth factor receptor-1 contributes to the corneal antiangiogenic barrier","volume":"91","author":"Ambati","year":"2007","journal-title":"Br. J. Ophthalmol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1001\/archopht.120.8.1063","article-title":"Angiostatin inhibits and regresses corneal neovascularization","volume":"120","author":"Ambati","year":"2002","journal-title":"Arch. Ophthalmol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1167\/iovs.04-1172","article-title":"Flt-1 intraceptors inhibit hypoxia-induced VEGF expression in vitro and corneal neovascularization in vivo","volume":"46","author":"Singh","year":"2005","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1097\/ICO.0b013e31802b4201","article-title":"Unique homologous siRNA blocks hypoxia-induced VEGF upregulation in human corneal cells and inhibits and regresses murine corneal neovascularization","volume":"26","author":"Singh","year":"2007","journal-title":"Cornea"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1111\/j.1600-0420.1997.tb00623.x","article-title":"Vascular endothelial growth factor (VEGF) in normal human corneal epithelium: Detection and physiological importance","volume":"75","year":"1997","journal-title":"Acta Ophthalmol. Scand."},{"key":"ref_15","first-page":"1112","article-title":"Correlation of VEGF expression by leukocytes with the growth and regression of blood vessels in the rat cornea","volume":"40","author":"Edelman","year":"1999","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1167\/iovs.01-1277","article-title":"VEGF-dependent conjunctivalization of the corneal surface","volume":"44","author":"Joussen","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.preteyeres.2006.09.001","article-title":"Regulation of corneal angiogenesis in limbal stem cell deficiency","volume":"25","author":"Ma","year":"2006","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.exer.2008.07.013","article-title":"Age-related changes in murine limbal lymphatic vessels and corneal lymphangiogenesis","volume":"87","author":"Hos","year":"2008","journal-title":"Exp. Eye Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1016\/j.exer.2008.08.007","article-title":"Improved semiautomatic method for morphometry of angiogenesis and lymphangiogenesis in corneal flatmounts","volume":"87","author":"Bock","year":"2008","journal-title":"Exp. Eye Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/s41596-018-0082-x","article-title":"Single-pot, solid-phase-enhanced sample preparation for proteomics experiments","volume":"14","author":"Hughes","year":"2019","journal-title":"Nat. Protoc."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5128","DOI":"10.1038\/s41467-018-07454-w","article-title":"Chromatogram libraries improve peptide detection and quantification by data independent acquisition mass spectrometry","volume":"9","author":"Searle","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1038\/s41592-019-0426-7","article-title":"Prosit: Proteome-wide prediction of peptide tandem mass spectra by deep learning","volume":"16","author":"Gessulat","year":"2019","journal-title":"Nat. Methods"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/s41592-019-0638-x","article-title":"DIA-NN: Neural networks and interference correction enable deep proteome coverage in high throughput","volume":"17","author":"Demichev","year":"2020","journal-title":"Nat. Methods"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1172\/JCI20465","article-title":"VEGF-A stimulates lymphangiogenesis and hemangiogenesis in inflammatory neovascularization via macrophage recruitment","volume":"113","author":"Cursiefen","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Daruich, A., Duncan, M., Robert, M.P., Lagali, N., Semina, E.V., Aberdam, D., Ferrari, S., Romano, V., des Roziers, C.B., and Benkortebi, R. (2022). Congenital aniridia beyond black eyes: From phenotype and novel genetic mechanisms to innovative therapeutic approaches. Prog. Retin. Eye Res., 101133.","DOI":"10.1016\/j.preteyeres.2022.101133"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1186\/s13287-021-02272-2","article-title":"Process development and safety evaluation of ABCB5(+) limbal stem cells as advanced-therapy medicinal product to treat limbal stem cell deficiency","volume":"12","author":"Norrick","year":"2021","journal-title":"Stem Cell Res. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1167\/iovs.10-5404","article-title":"Spontaneous lymphatic vessel formation and regression in the murine cornea","volume":"52","author":"Zhang","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Erusalimsky, J.D., and Kurz, D.J. (2006). Endothelial cell senescence. Handb. Exp. Pharmacol., 213\u2013248.","DOI":"10.1007\/3-540-36028-X_7"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.yjmcc.2003.11.010","article-title":"Vascular cell senescence and vascular aging","volume":"36","author":"Minamino","year":"2004","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1016\/S0002-9440(10)62355-3","article-title":"Spontaneous corneal hem- and lymphangiogenesis in mice with destrin-mutation depend on VEGFR3 signaling","volume":"166","author":"Cursiefen","year":"2005","journal-title":"Am. J. Pathol."},{"key":"ref_31","first-page":"1054","article-title":"Expression patterns of retinoblastoma and E2F family proteins during corneal development","volume":"41","author":"Francesconi","year":"2000","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1186\/s13287-020-01844-y","article-title":"Rat epidermal stem cells promote the angiogenesis of full-thickness wounds","volume":"11","author":"Huang","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.pharmthera.2014.02.013","article-title":"Mesenchymal stem\/stromal cells as a pharmacological and therapeutic approach to accelerate angiogenesis","volume":"143","author":"Bronckaers","year":"2014","journal-title":"Pharmacol. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1186\/s13287-017-0660-9","article-title":"Exosomes of human placenta-derived mesenchymal stem cells stimulate angiogenesis","volume":"8","author":"Komaki","year":"2017","journal-title":"Stem Cell Res. Ther."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Takeuchi, R., Katagiri, W., Endo, S., and Kobayashi, T. (2019). Exosomes from conditioned media of bone marrow-derived mesenchymal stem cells promote bone regeneration by enhancing angiogenesis. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0225472"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s11658-018-0133-x","article-title":"Limbal niche cells can reduce the angiogenic potential of cultivated oral mucosal epithelial cells","volume":"24","author":"Duan","year":"2019","journal-title":"Cell. Mol. Biol. Lett."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.jds.2020.03.007","article-title":"Dental pulp stem cells from human teeth with deep caries displayed an enhanced angiogenesis potential in vitro","volume":"16","author":"Chen","year":"2021","journal-title":"J. Dent. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"S12","DOI":"10.1016\/j.joen.2017.06.001","article-title":"Dental Pulp Stem Cells: Their Potential in Reinnervation and Angiogenesis by Using Scaffolds","volume":"43","author":"Lambrichts","year":"2017","journal-title":"J. Endod."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Youssef, A.R., Emara, R., Taher, M.M., Al-Allaf, F.A., Almalki, M., Almasri, M.A., and Siddiqui, S.S. (2019). Effects of mineral trioxide aggregate, calcium hydroxide, biodentine and Emdogain on osteogenesis, Odontogenesis, angiogenesis and cell viability of dental pulp stem cells. BMC Oral. Health, 19.","DOI":"10.1186\/s12903-019-0827-0"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Zaw, S.Y.M., Kaneko, T., Zaw, Z.C.T., Sone, P.P., Murano, H., Gu, B., Okada, Y., Han, P., Katsube, K.I., and Okiji, T. (2020). Crosstalk between dental pulp stem cells and endothelial cells augments angiogenic factor expression. Oral. Dis.","DOI":"10.1111\/odi.13341"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4141","DOI":"10.1364\/BOE.8.004141","article-title":"In-vivo imaging of the palisades of Vogt and the limbal crypts with sub-micrometer axial resolution optical coherence tomography","volume":"8","author":"Bizheva","year":"2017","journal-title":"Biomed. Opt. Express"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"8620172","DOI":"10.1155\/2018\/8620172","article-title":"The Role of Limbal Epithelial Stem Cells in Regulating Corneal (Lymph)angiogenic Privilege and the Micromilieu of the Limbal Niche following UV Exposure","volume":"2018","author":"Notara","year":"2018","journal-title":"Stem Cells Int."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"100768","DOI":"10.1016\/j.preteyeres.2019.07.001","article-title":"Immune reactions after modern lamellar (DALK, DSAEK, DMEK) versus conventional penetrating corneal transplantation","volume":"73","author":"Hos","year":"2019","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1515\/bc.2010.080","article-title":"Deletion of cathepsin H perturbs angiogenic switching, vascularization and growth of tumors in a mouse model of pancreatic islet cell cancer","volume":"391","author":"Gocheva","year":"2010","journal-title":"Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1080\/01902140802635517","article-title":"The chemokine CXCL16 is highly and constitutively expressed by human bronchial epithelial cells","volume":"35","author":"Day","year":"2009","journal-title":"Exp. Lung Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.7150\/thno.51507","article-title":"Metastatic colorectal cancer cells maintain the TGF\u03b2 program and use TGFBI to fuel angiogenesis","volume":"11","author":"Chiavarina","year":"2021","journal-title":"Theranostics"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1076\/ceyr.19.2.115.5325","article-title":"Heme oxygenase-1 gene expression as a stress index to ocular irritation","volume":"19","author":"Braunstein","year":"1999","journal-title":"Curr. Eye Res."},{"key":"ref_48","first-page":"858","article-title":"Complex role of heme oxygenase-1 in angiogenesis","volume":"6","author":"Dulak","year":"2004","journal-title":"Antioxid. Redox Signal."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2837","DOI":"10.1074\/jbc.275.4.2837","article-title":"Regulation of cyclooxygenase-2 by hypoxia and peroxisome proliferators in the corneal epithelium","volume":"275","author":"Bonazzi","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2612","DOI":"10.1016\/j.jcrs.2004.04.046","article-title":"Expression of cyclooxygenase-2 in corneal cells after photorefractive keratectomy and laser in situ keratomileusis in rabbits","volume":"30","author":"Miyamoto","year":"2004","journal-title":"J. Cataract. Refract. Surg."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"S46","DOI":"10.1097\/ICO.0b013e31812f6a71","article-title":"Effects of topical antiglaucoma medications on corneal epithelium as evaluated by gene expression patterns","volume":"26","author":"Okada","year":"2007","journal-title":"Cornea"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"242ra284","DOI":"10.1126\/scitranslmed.3008455","article-title":"COX-2 inhibition potentiates antiangiogenic cancer therapy and prevents metastasis in preclinical models","volume":"6","author":"Xu","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1076\/ceyr.19.4.300.5301","article-title":"The effect of selective cyclooxygenase-2 inhibitor on corneal angiogenesis in the rat","volume":"19","author":"Yamada","year":"1999","journal-title":"Curr. Eye Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.preteyeres.2010.01.002","article-title":"Novel aspects of corneal angiogenic and lymphangiogenic privilege","volume":"29","author":"Ellenberg","year":"2010","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.jtos.2019.06.001","article-title":"Thrombospondin-1 in ocular surface health and disease","volume":"17","author":"Foulsham","year":"2019","journal-title":"Ocul. Surf."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1016\/j.bbrc.2004.01.146","article-title":"Thrombospondin-1 accelerates wound healing of corneal epithelia","volume":"315","author":"Uno","year":"2004","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_57","first-page":"1735","article-title":"Thrombospondin 1 and type I repeat peptides of thrombospondin 1 specifically induce apoptosis of endothelial cells","volume":"57","author":"Guo","year":"1997","journal-title":"Cancer Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1084\/jem.20092277","article-title":"Thrombospondin 1 inhibits inflammatory lymphangiogenesis by CD36 ligation on monocytes","volume":"208","author":"Cursiefen","year":"2011","journal-title":"J. Exp. Med."},{"key":"ref_59","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_60","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/j.exer.2007.08.020","article-title":"Characterization of extracellular matrix components in the limbal epithelial stem cell compartment","volume":"85","author":"Dietrich","year":"2007","journal-title":"Exp. Eye Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s00418-002-0485-0","article-title":"Expression of IFI 16 in epithelial cells and lymphoid tissues","volume":"119","author":"Wei","year":"2003","journal-title":"Histochem. Cell. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"25381","DOI":"10.1038\/srep25381","article-title":"Up-regulation of Interferon-inducible protein 16 contributes to psoriasis by modulating chemokine production in keratinocytes","volume":"6","author":"Cao","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"F915","DOI":"10.1152\/ajprenal.00534.2017","article-title":"Expression of soluble epoxide hydrolase in renal tubular epithelial cells regulates macrophage infiltration and polarization in IgA nephropathy","volume":"315","author":"Wang","year":"2018","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Reisdorf, W.C., Xie, Q., Zeng, X., Xie, W., Rajpal, N., Hoang, B., Burgert, M.E., Kumar, V., Hurle, M.R., and Rajpal, D.K. (2019). Preclinical evaluation of EPHX2 inhibition as a novel treatment for inflammatory bowel disease. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0215033"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/j.exer.2008.02.001","article-title":"Topical interleukin-1 receptor antagonist inhibits inflammatory cell infiltration into the cornea","volume":"86","author":"Stapleton","year":"2008","journal-title":"Exp. Eye Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1016\/S0016-5085(98)70021-6","article-title":"Differential expression of interleukin 1 receptor antagonist isoforms in human intestinal epithelial cells","volume":"115","author":"Holt","year":"1998","journal-title":"Gastroenterology"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1136\/gut.46.3.350","article-title":"Human intestinal epithelial cells secrete interleukin-1 receptor antagonist and interleukin-8 but not interleukin-1 or interleukin-6","volume":"46","author":"Daig","year":"2000","journal-title":"Gut"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/0020-7292(95)02366-K","article-title":"Interleukin-1 receptor antagonist expression in epithelial cells of human endometrium","volume":"49","author":"Fukuda","year":"1995","journal-title":"Int. J. Gynaecol. Obstet."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1006\/cyto.1998.0451","article-title":"The human intracellular interleukin 1 receptor antagonist promoter appropriately regulates gene expression in keratinocytes and gastrointestinal epithelial cells in vivo","volume":"11","author":"Gabay","year":"1999","journal-title":"Cytokine"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/0014-4835(92)90197-Z","article-title":"Expression of interleukin-1\u03b1, interleukin-1\u03b2, and an interleukin-1 receptor antagonist in human retinal pigment epithelial cells","volume":"55","author":"Jaffe","year":"1992","journal-title":"Exp. Eye Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1165\/ajrcmb.21.3.3549","article-title":"Interleukin-1 receptor antagonist inhibits interleukin-8 expression in A549 respiratory epithelial cells infected in vitro with a replication-deficient recombinant adenovirus vector","volume":"21","author":"Schwarz","year":"1999","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1083\/jcb.133.4.921","article-title":"Inactivation of the integrin beta 6 subunit gene reveals a role of epithelial integrins in regulating inflammation in the lung and skin","volume":"133","author":"Huang","year":"1996","journal-title":"J. Cell Biol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.cyto.2014.07.253","article-title":"Antithrombin III, but not C1 esterase inhibitor reduces inflammatory response in lipopolysaccharide-stimulated human monocytes in an ex-vivo whole blood setting","volume":"70","author":"Kellner","year":"2014","journal-title":"Cytokine"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1182\/blood.V95.4.1117.002k12_1117_1123","article-title":"Recombinant human antithrombin III improves survival and attenuates inflammatory responses in baboons lethally challenged with Escherichia coli","volume":"95","author":"Minnema","year":"2000","journal-title":"Blood"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/S0168-8278(02)00059-4","article-title":"Antithrombin III prevents concanavalin A-induced liver injury through inhibition of macrophage inflammatory protein-2 release and production of prostacyclin in mice","volume":"36","author":"Nakamura","year":"2002","journal-title":"J. Hepatol."},{"key":"ref_76","first-page":"1553","article-title":"Inhibitory effects of antithrombin III against leukocyte rolling and infiltration during endotoxin-induced uveitis in rats","volume":"42","author":"Yamashiro","year":"2001","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.1016\/j.ajpath.2016.04.014","article-title":"Lung Epithelial Cell-Specific Expression of Human Lysosomal Acid Lipase Ameliorates Lung Inflammation and Tumor Metastasis in Lipa(\u2212\/\u2212) Mice","volume":"186","author":"Zhao","year":"2016","journal-title":"Am. J. Pathol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1159\/000023904","article-title":"Expression of histamine receptors in nasal epithelial cells and endothelial cells--the effects of sex hormones","volume":"115","author":"Hamano","year":"1998","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.1007\/s11095-007-9309-1","article-title":"Histamine-induced myosin light chain phosphorylation breaks down the barrier integrity of cultured corneal epithelial cells","volume":"24","author":"Guo","year":"2007","journal-title":"Pharm. Res."},{"key":"ref_80","first-page":"2562","article-title":"Human corneal epithelial cell functional responses to inflammatory agents and their antagonists","volume":"39","author":"Sharif","year":"1998","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_81","first-page":"550","article-title":"Design of eudragit RL nanoparticles by nanoemulsion method as carriers for ophthalmic drug delivery of ketotifen fumarate","volume":"19","author":"Soltani","year":"2016","journal-title":"Iran. J. Basic Med. Sci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2002732","DOI":"10.1183\/13993003.02732-2020","article-title":"The antimicrobial peptide S100A8\/A9 produced by airway epithelium functions as a potent and direct regulator of macrophage phenotype and function","volume":"59","author":"Durlanik","year":"2022","journal-title":"Eur. Respir. J."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"12564","DOI":"10.1038\/s41598-018-30021-8","article-title":"UV light-blocking contact lenses protect against short-term UVB-induced limbal stem cell niche damage and inflammation","volume":"8","author":"Notara","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1186\/s13287-019-1435-2","article-title":"Intra-pancreatic tissue-derived mesenchymal stromal cells: A promising therapeutic potential with anti-inflammatory and pro-angiogenic profiles","volume":"10","author":"Khiatah","year":"2019","journal-title":"Stem Cell Res. Ther."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2776","DOI":"10.1038\/s41598-022-06824-1","article-title":"Human adipose mesenchymal stem cells modulate inflammation and angiogenesis through exosomes","volume":"12","author":"Heo","year":"2022","journal-title":"Sci. Rep."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/13\/1731\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:01:59Z","timestamp":1760126519000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/13\/1731"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,27]]},"references-count":85,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["cells12131731"],"URL":"https:\/\/doi.org\/10.3390\/cells12131731","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,27]]}}}