{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T09:01:23Z","timestamp":1784883683232,"version":"3.55.0"},"reference-count":27,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>Background: Keratoconus is a progressive corneal ectasia characterised by extracellular matrix (ECM) loss and an emerging inflammatory component, for which no disease-modifying molecular therapy exists. Exosomes derived from limbal and mesenchymal stem cells are an attractive cell-free therapeutic modality, but the cargo that should be delivered is undefined, and no curated limbal stem-cell (LSC) exosome cargo dataset currently exists. Methods: We reanalysed a public keratoconus corneal RNA-sequencing dataset (GEO: GSE77938; discovery and replication cohorts) with DESeq2, defined a replicated differentially expressed gene (DEG) set, and performed Gene Ontology, KEGG and Reactome enrichment. A high-confidence protein\u2013protein interaction (PPI) network (STRING) identified hub genes. We integrated keratoconus disease-gene evidence (Open Targets Platform) and documented extracellular-vesicle cargo (ExoCarta, Vesiclepedia) and computed a transparent Cargo Prioritization Score (CPS) to nominate candidate LSC-exosome therapeutic cargo. Results: A total of 1677 DEGs were detected in discovery (152 up, 1525 down) and 1380 were replicated. Enrichment was dominated by extracellular matrix organisation; adaptive immune response; and mononuclear cell differentiation. Network analysis nominated ECM and immune hub genes. The CPS prioritised COL1A1, FN1, COL4A1, COL3A1, COL5A1, MMP1 as leading restoration-cargo candidates, all documented as EV cargo and present in the mesenchymal stem-cell EV reference proteome. Conclusions: This fully reproducible, real-data framework provides a ranked, evidence-traceable shortlist of candidate LSC-exosome cargo for keratoconus and an explicit account of current data gaps to guide experimental validation.<\/jats:p>","DOI":"10.3390\/bioengineering13080853","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T07:36:13Z","timestamp":1784878573000},"page":"853","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["An Integrative Bioinformatics Framework Nominates Candidate Limbal Stem-Cell Exosome Cargo for Keratoconus by Coupling Corneal Transcriptomics, Disease-Gene Evidence and Extracellular-Vesicle Repositories"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5527-690X","authenticated-orcid":false,"given":"Chun-Chieh","family":"Chao","sequence":"first","affiliation":[{"name":"Graduate Institute of Injury Prevention and Control, College of Public Health, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"Department of Emergency Medicine, Taipei Medical University Hospital, Taipei 110301, Taiwan"},{"name":"Department of Emergency Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsieh-Tsung Ethan","family":"Shen","sequence":"additional","affiliation":[{"name":"YD Bio Limited, Taipei 115603, Taiwan"},{"name":"Division of Clinical Cariology and Endodontology, Department of Oral Rehabilitation, School of Dentistry, Health Sciences University of Hokkaido, Tobetsu 061-0293, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3806-9719","authenticated-orcid":false,"given":"Bo-Xiang Benjamin","family":"Zhang","sequence":"additional","affiliation":[{"name":"YD Bio Limited, Taipei 115603, Taiwan"},{"name":"Division of Clinical Cariology and Endodontology, Department of Oral Rehabilitation, School of Dentistry, Health Sciences University of Hokkaido, Tobetsu 061-0293, Japan"},{"name":"Ph.D. Program in Medical Neuroscience, College of Medical Science and Technology, Taipei Medical University and National Health Research Institutes, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4840-7714","authenticated-orcid":false,"given":"Ting-Hsuan","family":"Chao","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, College of Letter and Science, University of California, Berkeley, CA 94720, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien-Yi","family":"Tu","sequence":"additional","affiliation":[{"name":"Executive Master Program of Business Administration in Biotechnology, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen-hsin","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Taipei Medical University Hospital, Taipei 110301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101559","DOI":"10.1016\/j.clae.2021.101559","article-title":"Keratoconus: An updated review","volume":"45","author":"Carracedo","year":"2022","journal-title":"Contact Lens Anterior Eye J. 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