{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T15:15:03Z","timestamp":1788534903900,"version":"build-2803163510"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"vor","delay-in-days":17,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015938","name":"Hillman Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015938","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001607","name":"Eye and Ear Foundation of Pittsburgh","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001607","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institutes of Health (NIH) Regenerative Medicine Innovation Project","award":["U01 EY035252"],"award-info":[{"award-number":["U01 EY035252"]}]},{"name":"Research to Prevent Blindness and National Eye Institute","award":["P30"],"award-info":[{"award-number":["P30"]}]},{"name":"Research to Prevent Blindness and National Eye Institute","award":["EY008098"],"award-info":[{"award-number":["EY008098"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Human corneal stromal stem cells (hCSSCs), which exhibit mesenchymal stem cell (MSC) features, prevent fibrotic scarring and promote regeneration of injured stromal tissue, thereby restoring corneal clarity in mice. These therapeutic effects rely on hCSSCs\u2019 ability to respond to early inflammatory cues, suppress chronic neutrophil infiltration, and inhibit fibrosis. In this study, we examined the responses of hCSSCs to transient pro-inflammatory M1 stimulation and characterized the exosomes (Exo) they secreted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We evaluated the expression of full-length protein-coding human TGFB3 mRNA molecules in purified Exo, and investigated Exo uptake, induction of human transforming growth factor \u03b23 (hTGF\u03b23) protein expression, and the effects of different hTGF\u03b23\/\u03b21 ratios on myofibroblast generation from human corneal stromal keratocytes (CSKs) and stromal fibroblasts (SFs). The anti-scarring effect of hCSSC-Exo enriched in TGFB3 mRNA was assessed in a mouse model of acute corneal stromal injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our results showed that hCSSC-Exo contained TGFB3 mRNA transcripts, and their abundance increased following pro-inflammatory M1 stimulation. Exo uptake enhanced hTGF\u03b23 protein expression in hCSKs, and a higher hTGF\u03b23\/\u03b21 ratio in hCSKs and hSFs suppressed expression of \u03b1-smooth muscle actin and TGF\u03b21-induced myofibroblast differentiation. In vivo, topical treatment with M1-primed hCSSC-Exo reduced corneal opacity compared with sham-treated controls. Notably, hCSSC-Exo enriched with TGFB3 mRNA demonstrated greater scar-reducing and wound-healing efficacy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>M1-primed hCSSC-Exo containing protein-coding TGFB3 mRNA significantly inhibited corneal opacity and promoted scar-free healing in injured mouse corneas. These findings support the anti-fibrotic and regenerative potential of hCSSC-Exo, which can be developed as a cell-free therapeutic strategy for corneal fibrosis and scarring.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/stcltm\/szag079","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T11:50:26Z","timestamp":1786535426000},"source":"Crossref","is-referenced-by-count":0,"title":["M1-primed human corneal stromal stem cell-derived exosomes delivering protein-coding transforming growth factor-\u03b23 RNA promote corneal regeneration"],"prefix":"10.1093","volume":"15","author":[{"given":"Mithun","family":"Santra","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Corneal Regeneration Lab, University of Pittsburgh School of Medicine , Pittsburgh, PA 15219,","place":["United 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States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Chandran","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Corneal Regeneration Lab, University of Pittsburgh School of Medicine , Pittsburgh, PA 15219,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia T","family":"Coelho","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Corneal Regeneration Lab, University of Pittsburgh School of Medicine , Pittsburgh, PA 15219,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ella J","family":"Dewald","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Corneal Regeneration Lab, University of Pittsburgh School of Medicine , Pittsburgh, PA 15219,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Pittsburgh School of Medicine , Pittsburgh, PA 15219,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha L","family":"Funderburgh","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Corneal Regeneration Lab, University of Pittsburgh School of Medicine , Pittsburgh, PA 15219,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepinder K","family":"Dhaliwal","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Corneal Regeneration Lab, University of Pittsburgh School of Medicine , Pittsburgh, PA 15219,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin D","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Pittsburgh School of Medicine , Pittsburgh, PA 15219,","place":["United States"]},{"name":"Department of Bioengineering, University of Pittsburgh , Pittsburgh, PA 15219,","place":["United States"]},{"name":"Institute for Synthetic Biology, University of Pittsburgh , Pittsburgh, PA 15219,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishal","family":"Jhanji","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Corneal Regeneration Lab, University of Pittsburgh School of Medicine , Pittsburgh, PA 15219,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8445-3669","authenticated-orcid":false,"given":"Gary H F","family":"Yam","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Corneal Regeneration Lab, University of Pittsburgh School of Medicine , Pittsburgh, PA 15219,","place":["United 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