Intravenous and intranasal Muse cell administration delivers cognitive and histologic improvements in an Alzheimer’s disease model

Intravenous and intranasal Muse cell administration delivers cognitive and histologic improvements in an Alzheimer’s disease model | 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 Brief Communication Intravenous and intranasal Muse cell administration delivers cognitive and histologic improvements in an Alzheimer’s disease model Mari Dezawa, Keitaro Shiraishi, Yoshihiro Kushida, Yasumasa Kuroda, and 10 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8958458/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Mesenchymal stromal cells (MSCs) contain several percentages of SSEA-3+ pluripotent-like Muse cells. We compared human bone marrow–derived Muse cells with MSC controls delivered intravenously (IV) or intranasally (IN) in 3 month old 5xFAD mice without immunosuppression. Light sheet imaging of mCherry labeled cells showed markedly greater brain retention of Muse cells at day 7 after IN delivery compared with MSCs. At 16 weeks, human cells, detected by anti–human mitochondria, human nuclear Ku80, and Alu ddPCR, were highly persistent in both Muse groups with neural and microglial marker expression. Muse treatment reduced amyloid β plaque burden and preserved pre-onset Y maze and Morris water maze performance through 16 weeks, with similar outcomes after IV and IN delivery. These findings support further evaluation of IN Muse cell delivery for AD cell therapy. Health sciences/Diseases/Neurological disorders/Dementia/Alzheimer's disease Biological sciences/Stem cells/Adult stem cells/Mesenchymal stem cells Full Text Additional Declarations Yes there is potential Competing Interest. MuseCell Innovations PTE Ltd (MCI, Singapore) holds exclusive licensing and patents for Muse Cells. A statement of ethics approval: while this is not a human study, our study was approved by the Ethics Committees of Toyama University (No. A2021med-252 and No. G2021med-60) and Tohoku University (No. 2025NdA-024) for the animal study, as mentioned in the Method file, not in the main text.A statement on participant consent: Since our study is neither a human study nor a clinical study, participant consent is not required. Supplementary Files SuppleMov2Muse1dayC.mp4 Three-dimensional light sheet imaging of intranasally injected mCherry-hMuse cells in the brain at day 1 SuppleMovMSC1dayC.mp4 Three-dimensional light sheet imaging of intranasally injected mCherry-hMSCs in the brain at day 1 ExtendedDataFVXXX.pdf Extended Data SuppeMov3MSC7daysC.mp4 Three-dimensional light sheet imaging of intranasally injected mCherry-hMSCs in the brain at day 7 SuppleMov4Muse7daysC.mp4 Three-dimensional light sheet imaging of intranasally injected mCherry-hMuse cells in the brain at day 7 Cite Share Download PDF Status: Under Review 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. 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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-8958458","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Brief Communication","associatedPublications":[],"authors":[{"id":596905571,"identity":"ad90e8b3-512d-41ab-9ee4-f2185a585486","order_by":0,"name":"Mari 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