Thrombospondin Encapsulated Dense Particles accelerate wound healing and downregulate fibrotic phenotypes

preprint OA: gold CC-BY-4.0
📄 Open PDF Full text JSON View at publisher
AI-generated deep summary by claude@2026-07, 2026-07-03 · read from full text

This preprint investigates extracellular particles by screening 15 fluorescent extracellular vesicle (EV) markers across four adherent cell lines using nanoflow cytometry, identifying TSPAN14 as the best EV marker in three lines while noting that in multiple lines less than half of extracellular particles are labeled by the top markers. The authors characterize an EV-marker–negative extracellular particle subpopulation as detergent-resistant, non-lipophilic, dense particles with thrombospondin shells (ThrEDs), which they report are ubiquitous, contain extracellular matrix regulators, and are released after cell stress. ThrEDs were found to accelerate scratch-wound closure and downregulate fibrotic phenotypes in Dupuytren’s disease patient myofibroblasts, with the major caveat that the work is a preprint that has not been peer reviewed. This paper is centrally about endometriosis and/or adenomyosis— it is included in the corpus via keyword match rather than explicit discussion of endometriosis or adenomyosis.

Read from the paper's body, not the abstract. Not a substitute for reading the paper. No clinical advice. How this works

Abstract

Abstract Extracellular particles (EP) released by cells are heterogenous, with extracellular vesicles (EV) believed to be the major component. To investigate different EV subpopulations, we conducted a panel screen of 15 fluorescent EV markers in 4 adherent cell lines. Nanoflow cytometry identifies TSPAN14 as the best EV marker in 3 of 4 cell lines. Surprisingly, less than 50% of EPs are labelled by the top 2 EV markers in half the cell lines. The EV marker negative EPs are detergent resistant, non-lipophilic, dense and have Thrombospondin shells by dSTORM; and were thus named Thrombospondin Encapsulated Dense particles (ThrEDs). ThrEDs are ubiquitous, contain extracellular matrix regulators and are released following cell stress. ThrEDs accelerate scratch-wound closure and downregulate the fibrotic phenotype in Dupuytren’s disease patient myofibroblasts. The TSP-1 C-terminus is exposed on the surface of ThrEDs, opening engineering applications.
Full text 15,073 characters · extracted from preprint-html · click to expand
Thrombospondin Encapsulated Dense Particles accelerate wound healing and downregulate fibrotic phenotypes | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Thrombospondin Encapsulated Dense Particles accelerate wound healing and downregulate fibrotic phenotypes Michael Dustin, Claire Staton, Marcus Widdess, Ashwin Jainarayanan, and 12 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7943553/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Extracellular particles (EP) released by cells are heterogenous, with extracellular vesicles (EV) believed to be the major component. To investigate different EV subpopulations, we conducted a panel screen of 15 fluorescent EV markers in 4 adherent cell lines. Nanoflow cytometry identifies TSPAN14 as the best EV marker in 3 of 4 cell lines. Surprisingly, less than 50% of EPs are labelled by the top 2 EV markers in half the cell lines. The EV marker negative EPs are detergent resistant, non-lipophilic, dense and have Thrombospondin shells by dSTORM; and were thus named Thrombospondin Encapsulated Dense particles (ThrEDs). ThrEDs are ubiquitous, contain extracellular matrix regulators and are released following cell stress. ThrEDs accelerate scratch-wound closure and downregulate the fibrotic phenotype in Dupuytren’s disease patient myofibroblasts. The TSP-1 C-terminus is exposed on the surface of ThrEDs, opening engineering applications. Biological sciences/Cell biology/Cell signalling/Extracellular signalling molecules Biological sciences/Drug discovery/Biologics/Cell therapies Health sciences/Diseases/Immunological disorders/Inflammatory diseases Biological sciences/Cell biology/Mechanisms of disease Biological sciences/Cell biology/Cell adhesion/Extracellular matrix ThrED SMAP NVEP subpopulation proteinaceous particle shell delivery wound healing fibrosis Full Text Additional Declarations Yes there is potential Competing Interest. M.L. Dustin and C.C. Staton have filed a provisional patent on proteinaceous particles: ThrEDs isolation and engineering. Supplementary Files StatonetalThrEDsNCBsupp.pdf Supplemental Figures and legends Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7943553","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":537121952,"identity":"915c5208-c4cd-473c-b633-acb059e75b7f","order_by":0,"name":"Michael Dustin","email":"data:image/png;base64,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","orcid":"https://orcid.org/0000-0003-4983-6389","institution":"Kennedy Institute of Rheumatology","correspondingAuthor":true,"prefix":"","firstName":"Michael","middleName":"","lastName":"Dustin","suffix":""},{"id":537121953,"identity":"1d59ef08-f381-4931-bc8e-afb567fbf036","order_by":1,"name":"Claire Staton","email":"","orcid":"","institution":"University of Oxford","correspondingAuthor":false,"prefix":"","firstName":"Claire","middleName":"","lastName":"Staton","suffix":""},{"id":537121954,"identity":"c02c3f3a-205b-439f-b5e2-0f8b71aa24ed","order_by":2,"name":"Marcus Widdess","email":"","orcid":"","institution":"University of Oxford","correspondingAuthor":false,"prefix":"","firstName":"Marcus","middleName":"","lastName":"Widdess","suffix":""},{"id":537121955,"identity":"43ed7e03-94bf-49f2-8583-93e2fa348be6","order_by":3,"name":"Ashwin Jainarayanan","email":"","orcid":"","institution":"University of Oxford","correspondingAuthor":false,"prefix":"","firstName":"Ashwin","middleName":"","lastName":"Jainarayanan","suffix":""},{"id":537121956,"identity":"a6286620-caf2-4948-8f52-d0920ce1bd26","order_by":4,"name":"Anna Hoyle","email":"","orcid":"","institution":"University of Oxford","correspondingAuthor":false,"prefix":"","firstName":"Anna","middleName":"","lastName":"Hoyle","suffix":""},{"id":537121957,"identity":"30f3e9d2-d049-46d2-8c68-43d0a0c25243","order_by":5,"name":"Lynn Williams","email":"","orcid":"","institution":"University of Oxford","correspondingAuthor":false,"prefix":"","firstName":"Lynn","middleName":"","lastName":"Williams","suffix":""},{"id":537121958,"identity":"fe424191-d60f-4d13-b9df-c1931a147e22","order_by":6,"name":"Delaney Dominey-Foy","email":"","orcid":"","institution":"University of Oxford","correspondingAuthor":false,"prefix":"","firstName":"Delaney","middleName":"","lastName":"Dominey-Foy","suffix":""},{"id":537121959,"identity":"eb96903f-6ba0-4389-9bd4-5c3e92933f71","order_by":7,"name":"Cristina Ulivieri","email":"","orcid":"","institution":"University of Siena","correspondingAuthor":false,"prefix":"","firstName":"Cristina","middleName":"","lastName":"Ulivieri","suffix":""},{"id":537121960,"identity":"63c22276-b7ac-491f-9fde-84c2e15f41be","order_by":8,"name":"Iolanda Vendrell","email":"","orcid":"","institution":"University of Oxford","correspondingAuthor":false,"prefix":"","firstName":"Iolanda","middleName":"","lastName":"Vendrell","suffix":""},{"id":537121961,"identity":"593a2145-2b16-45bf-bcd5-e9d7bf6a52fd","order_by":9,"name":"Roman Fischer","email":"","orcid":"https://orcid.org/0000-0002-9715-5951","institution":"University of Oxford","correspondingAuthor":false,"prefix":"","firstName":"Roman","middleName":"","lastName":"Fischer","suffix":""},{"id":537121962,"identity":"f495e77a-c28b-4c31-9efe-2e1f29b90f76","order_by":10,"name":"Kim Midwood","email":"","orcid":"https://orcid.org/0000-0002-8813-2977","institution":"Kennedy Institute of Rheumatology","correspondingAuthor":false,"prefix":"","firstName":"Kim","middleName":"","lastName":"Midwood","suffix":""},{"id":537121963,"identity":"c7d61b22-8402-4d29-b8e4-6f89557265c4","order_by":11,"name":"Cosima Baldari","email":"","orcid":"","institution":"University of Siena","correspondingAuthor":false,"prefix":"","firstName":"Cosima","middleName":"","lastName":"Baldari","suffix":""},{"id":537121964,"identity":"91bb36bc-6e52-4c8c-bb72-e3c60804d5b6","order_by":12,"name":"Jagdeep Nanchahal","email":"","orcid":"","institution":"University of Oxford","correspondingAuthor":false,"prefix":"","firstName":"Jagdeep","middleName":"","lastName":"Nanchahal","suffix":""},{"id":537121965,"identity":"81b4f1e8-08e3-4253-8c48-647ce759de3d","order_by":13,"name":"Dhanu Gupta","email":"","orcid":"","institution":"University of Oxford","correspondingAuthor":false,"prefix":"","firstName":"Dhanu","middleName":"","lastName":"Gupta","suffix":""},{"id":537121966,"identity":"43e0fa84-cfc2-4f77-ac75-633eec08b45e","order_by":14,"name":"Pablo Céspedes","email":"","orcid":"https://orcid.org/0000-0002-1641-4107","institution":"University of Oxford","correspondingAuthor":false,"prefix":"","firstName":"Pablo","middleName":"","lastName":"Céspedes","suffix":""},{"id":537121967,"identity":"05499fd8-7c39-4336-8369-1c73c22bac6b","order_by":15,"name":"Matthew Wood","email":"","orcid":"","institution":"University of Oxford","correspondingAuthor":false,"prefix":"","firstName":"Matthew","middleName":"","lastName":"Wood","suffix":""}],"badges":[],"createdAt":"2025-10-26 16:54:02","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7943553/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7943553/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":97671905,"identity":"66ffb738-2abd-4dbc-999b-b79e7cdd5fac","added_by":"auto","created_at":"2025-12-08 09:33:19","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5063733,"visible":true,"origin":"","legend":"Article File","description":"","filename":"StatonetalThrEDsNCBmain.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7943553/v1_covered_e857ed5f-fced-43bb-9f47-b703ad3386b2.pdf"},{"id":94775875,"identity":"c4e55a13-9cbc-4faf-8911-c13bb7476528","added_by":"auto","created_at":"2025-10-30 14:47:59","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":7498615,"visible":true,"origin":"","legend":"Supplemental Figures and legends","description":"","filename":"StatonetalThrEDsNCBsupp.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7943553/v1/f7ef6ae02c35bc331fe3694d.pdf"}],"financialInterests":"\u003cb\u003eYes\u003c/b\u003e there is potential Competing Interest.\nM.L. Dustin and C.C. Staton have filed a provisional patent on proteinaceous particles: ThrEDs isolation and engineering.","formattedTitle":"Thrombospondin Encapsulated Dense Particles accelerate wound healing and downregulate fibrotic phenotypes","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"ThrED, SMAP, NVEP, subpopulation, proteinaceous particle shell, delivery, wound healing, fibrosis","lastPublishedDoi":"10.21203/rs.3.rs-7943553/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7943553/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Extracellular particles (EP) released by cells are heterogenous, with extracellular vesicles (EV) believed to be the major component. To investigate different EV subpopulations, we conducted a panel screen of 15 fluorescent EV markers in 4 adherent cell lines. Nanoflow cytometry identifies TSPAN14 as the best EV marker in 3 of 4 cell lines. Surprisingly, less than 50% of EPs are labelled by the top 2 EV markers in half the cell lines. The EV marker negative EPs are detergent resistant, non-lipophilic, dense and have Thrombospondin shells by dSTORM; and were thus named Thrombospondin Encapsulated Dense particles (ThrEDs). ThrEDs are ubiquitous, contain extracellular matrix regulators and are released following cell stress. ThrEDs accelerate scratch-wound closure and downregulate the fibrotic phenotype in Dupuytren’s disease patient myofibroblasts. The TSP-1 C-terminus is exposed on the surface of ThrEDs, opening engineering applications.","manuscriptTitle":"Thrombospondin Encapsulated Dense Particles accelerate wound healing and downregulate fibrotic phenotypes","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-30 14:47:55","doi":"10.21203/rs.3.rs-7943553/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3fa1ea86-1f0f-4bbc-a24c-a401063ae77d","owner":[],"postedDate":"October 30th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":57120084,"name":"Biological sciences/Cell biology/Cell signalling/Extracellular signalling molecules"},{"id":57120085,"name":"Biological sciences/Drug discovery/Biologics/Cell therapies"},{"id":57120086,"name":"Health sciences/Diseases/Immunological disorders/Inflammatory diseases"},{"id":57120087,"name":"Biological sciences/Cell biology/Mechanisms of disease"},{"id":57120088,"name":"Biological sciences/Cell biology/Cell adhesion/Extracellular matrix"}],"tags":[],"updatedAt":"2025-12-05T18:00:22+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-30 14:47:55","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7943553","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7943553","identity":"rs-7943553","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}

Text is read by the "Ask this paper" AI Q&A widget below. Extraction quality varies by source — PMC NXML preserves structure cleanly, OA-HTML may include some navigation residue, and OA-PDF can have broken hyphenation. The publisher copy (via DOI) is the canonical version.

My notes (saved in your browser only)

Ask this paper AI returns verbatim quotes from the full text · source: preprint-html

Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works

Citation neighborhood (no data yet)

We don't have any in-corpus citations linked to this paper yet. This is a recent paper (2025) — citers typically take a year or two to land, and the OpenAlex reference graph may still be filling in.

Source provenance

europepmc
last seen: 2026-05-20T01:45:00.602351+00:00
unpaywall
last seen: 2026-05-21T05:10:58.409756+00:00
License: CC-BY-4.0