{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T05:00:43Z","timestamp":1785474043834,"version":"3.56.0"},"reference-count":55,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["TR002380"],"award-info":[{"award-number":["TR002380"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"award":["TR002380"],"award-info":[{"award-number":["TR002380"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R21 AI152318"],"award-info":[{"award-number":["R21 AI152318"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R21 AI145356"],"award-info":[{"award-number":["R21 AI145356"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"award":["R21 AI152318"],"award-info":[{"award-number":["R21 AI152318"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R21 AI145356"],"award-info":[{"award-number":["R21 AI145356"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart Lung and Blood Institute","doi-asserted-by":"crossref","award":["R01 HL164520"],"award-info":[{"award-number":["R01 HL164520"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"award":["R01 HL164520"],"award-info":[{"award-number":["R01 HL164520"]}],"id":[{"id":"https:\/\/ror.org\/012pb6c26","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Stem cell-derived \u03b2 (SC-\u03b2) cells are a promising therapy for type 1 diabetes (T1D), but their long-term efficacy is limited by immune-mediated graft rejection. Platelet-derived exosome product (PEP) has emerged as a novel immunomodulatory agent, although its effect on SC-\u03b2 cell xenograft rejection remains unclear. Here, we evaluated PEP in stimulated human peripheral blood mononuclear cells (PBMCs) and in an immunocompetent mouse model of SC-\u03b2 cell transplantation under the kidney capsule. Immune-related gene expression was assessed by quantitative PCR, immune cell infiltration by immunofluorescence, and graft function by circulating human insulin. In vitro, PEP reduced NK-cell-associated gene expression, including NK1.1, EOMES, and KLRK1, and increased IL-10 expression. In vivo, untreated SC-\u03b2 cell xenografts showed progressive immune infiltration and loss of detectable human insulin by day 14, whereas PEP-treated grafts retained detectable insulin through day 14 across co-transplantation, pretreatment, and systemic administration strategies. PEP co-transplantation delayed, but did not prevent, xenograft rejection, with graft loss observed by day 21. This delay was associated with reduced NK1.1+ cell infiltration and lower expression of selected inflammatory and rejection-associated markers, including NK1.1, Nos2, and Nlrp3. These findings suggest that PEP modulates graft-associated immune responses and may serve as an adjunct immunomodulatory strategy for stem cell-based therapies for type 1 diabetes. Further studies are needed to evaluate sustained graft durability, safety, and translational efficacy.<\/jats:p>","DOI":"10.3390\/cells15151367","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T11:45:14Z","timestamp":1785325514000},"page":"1367","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Platelet-Derived Exosome Product Prolongs Stem Cell-Derived \u03b2-Cell Graft Survival and Is Associated with Reduced Nk Cell Infiltration and Immunomodulation"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1291-573X","authenticated-orcid":false,"given":"Zenith","family":"Khashim","sequence":"first","affiliation":[{"name":"Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9384-7827","authenticated-orcid":false,"given":"Swikriti","family":"Shrestha","sequence":"additional","affiliation":[{"name":"Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaimaa","family":"Hassoun","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7975-1365","authenticated-orcid":false,"given":"Ethan W.","family":"Law","sequence":"additional","affiliation":[{"name":"Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8991-3882","authenticated-orcid":false,"given":"Anna Marie R.","family":"Schornack","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Lacap","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle J.","family":"Beetler","sequence":"additional","affiliation":[{"name":"Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, MN 55905, USA"},{"name":"Department of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL 32224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7410-923X","authenticated-orcid":false,"given":"Gabriel J.","family":"Weigel","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL 32224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7336-517X","authenticated-orcid":false,"given":"Lauren T.","family":"Jennings","sequence":"additional","affiliation":[{"name":"Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Becher","sequence":"additional","affiliation":[{"name":"Rion Inc., Rochester, MN 55902, USA"},{"name":"Department of Cardiovascular Disease, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5882-709X","authenticated-orcid":false,"given":"Chris","family":"Paradise","sequence":"additional","affiliation":[{"name":"Rion Inc., Rochester, MN 55902, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atta","family":"Behfar","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Disease, Mayo Clinic, Rochester, MN 55905, USA"},{"name":"Van Cleve Cardiac Regenerative Medicine Program, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3093-1810","authenticated-orcid":false,"given":"DeLisa","family":"Fairweather","sequence":"additional","affiliation":[{"name":"Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, MN 55905, USA"},{"name":"Department of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL 32224, USA"},{"name":"Department of 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