{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T18:14:37Z","timestamp":1793643277271,"version":"4.5.1"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:p>\n                    Metabolic syndrome (MetS) profoundly changes the contents of mesenchymal stem cells and mesenchymal stem cells\u2013derived extracellular vesicles (EVs). The anti-inflammatory TGF-\u03b2 (transforming growth factor-\u03b2) is selectively enriched in EVs from Lean but not from MetS pigs, but the functional impact of this endowment remains unknown. We hypothesized that Lean-EVs more effectively induce regulatory T cells in injured kidneys. Five groups of pigs (n=7 each) were studied after 16 weeks of diet-induced MetS and unilateral renal artery stenosis (RAS; MetS+RAS). Two groups of MetS+RAS were treated 4 weeks earlier with an intrarenal injection of either Lean-EVs or MetS-EVs. MetS+RAS had lower renal volume, renal blood flow, and glomerular filtration rate than MetS pigs. Compared with Lean-EVs, MetS-EVs were less effective in improving renal function and decreasing tubular injury and fibrosis in MetS+RAS. Lean-EVs upregulated TGF-\u03b2 expression in stenotic kidney and increased regulatory T cells numbers more prominently. Furthermore, markedly upregulated anti-inflammatory M2 macrophages reduced proinflammatory M1 macrophages, and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells were detected in stenotic kidneys treated with Lean-EVs compared with MetS-EVs, and renal vein levels of interleukin-1\u03b2 were reduced. In vitro, coculture of Lean-EVs with activated T cells led to greater TGF-\u03b2-dependent regulatory T cells induction than did MetS-EVs. Therefore, the beneficial effects of mesenchymal stem cells\u2013derived EVs on injured kidneys might be partly mediated by their content of TGF-\u03b2 signaling components, which permitting increased Treg preponderance. Modulating EV cargo and transforming their functionality might be useful for renal repair.\n                  <\/jats:p>","DOI":"10.1161\/hypertensionaha.119.14546","type":"journal-article","created":{"date-parts":[[2020,3,30]],"date-time":"2020-03-30T05:00:21Z","timestamp":1585544421000},"page":"1223-1232","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":62,"title":["Mesenchymal Stem Cell\u2013Derived Extracellular Vesicles Induce Regulatory T Cells to Ameliorate Chronic Kidney Injury"],"prefix":"10.1161","volume":"75","author":[{"given":"Turun","family":"Song","sequence":"first","affiliation":[{"name":"From the Division of Nephrology and Hypertension (T.S., A.E., X.Z., Y.Z., J.D.K., H.T., K.L.J., J.R.W., L.O.L.), Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Eirin","sequence":"additional","affiliation":[{"name":"From the Division of Nephrology and Hypertension (T.S., A.E., X.Z., Y.Z., J.D.K., H.T., K.L.J., J.R.W., L.O.L.), Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyang","family":"Zhu","sequence":"additional","affiliation":[{"name":"From the Division of Nephrology and Hypertension (T.S., A.E., X.Z., Y.Z., J.D.K., H.T., K.L.J., J.R.W., L.O.L.), Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhao","sequence":"additional","affiliation":[{"name":"From the Division of Nephrology and Hypertension (T.S., A.E., X.Z., Y.Z., J.D.K., H.T., K.L.J., J.R.W., L.O.L.), Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James D.","family":"Krier","sequence":"additional","affiliation":[{"name":"From the Division of Nephrology and Hypertension (T.S., A.E., X.Z., Y.Z., J.D.K., H.T., K.L.J., J.R.W., L.O.L.), Mayo Clinic, Rochester, 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