{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:53:12Z","timestamp":1791417192180,"version":"4.3.3"},"reference-count":64,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T00:00:00Z","timestamp":1646611200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T00:00:00Z","timestamp":1646611200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870651"],"award-info":[{"award-number":["81870651"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81600723"],"award-info":[{"award-number":["81600723"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010041","name":"Tianjin Science and Technology Committee","doi-asserted-by":"publisher","award":["20YFZCSY00990"],"award-info":[{"award-number":["20YFZCSY00990"]}],"id":[{"id":"10.13039\/501100010041","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010041","name":"Tianjin Municipal Science and Technology Commission","doi-asserted-by":"crossref","award":["20JCZDJC00100"],"award-info":[{"award-number":["20JCZDJC00100"]}],"id":[{"id":"10.13039\/501100010041","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Stem Cell Res Ther"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Autoimmune uveitis\u00a0is\u00a0a\u00a0sight-threatening intraocular inflammation mainly caused by immune dysregulation. The development of safe and effective therapeutic approaches is urgently needed. Small extracellular vesicles (sEVs) derived from mesenchymal stem cells (MSCs) have been demonstrated to inhibit autoimmune responses; however, the immunosuppressive effect of MSC-sEVs is too weak for clinical transfer. In the current study, we investigated the therapeutic effect of IL-10-overexpressing MSC-sEVs (sEV-IL10) on experimental autoimmune uveitis (EAU) and studied\u00a0the underlying\u00a0mechanism.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Mice were randomly grouped and received a single tail vein injection of different sEVs (50\u00a0\u03bcg) or PBS on day 11 post-immunization. The clinical and histological scores were graded, and the percentage of T helper cell was measured. To investigate the effect of sEVs on the proliferation of T-cells and the differentiation of Th1, Th17 and Treg cells, T-cells were cocultured with sEVs under the corresponding culture conditions. After labeled with PKH-26, sEVs were traced both in vivo and in vitro.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Compared with normal or vector sEV-treated groups, mice in the sEV-IL10-treated group had lower clinical and histological scores with lower percentages of Th1 and Th17 cells in the eyes and higher percentages of Treg cells in the spleen and draining lymph nodes (LN). Furthermore,\u00a0sEV-IL10 enhanced the suppressive effect of MSC-sEVs on the proliferation of T-cells and differentiation of Th1 and Th17 cells, whereas upregulated the differentiation of Treg cells. Both in vivo and in vitro experiments demonstrated that MSC-sEVs were rapidly enriched in target tissues and internalized by T-cells.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>These results suggested that sEV-IL10 effectively ameliorates EAU by regulating the proliferation and differentiation of T-cells, indicating sEVs as a potential novel therapy for autoimmune uveitis or other autoimmune diseases.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13287-022-02780-9","type":"journal-article","created":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T09:02:58Z","timestamp":1646643778000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Effect of small extracellular vesicles derived from IL-10-overexpressing mesenchymal stem cells on experimental autoimmune uveitis"],"prefix":"10.1186","volume":"13","author":[{"given":"Yongtao","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinjun","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaorong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4898-4152","authenticated-orcid":false,"given":"Xiaomin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,3,7]]},"reference":[{"issue":"1106","key":"2780_CR1","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1136\/postgradmedj-2017-134891","volume":"93","author":"U Krishna","year":"2017","unstructured":"Krishna U, Ajanaku D, Denniston AK, Gkika T. Uveitis: a sight-threatening disease which can impact all systems. Postgrad Med J. 2017;93(1106):766\u201373.","journal-title":"Postgrad Med J"},{"issue":"1","key":"2780_CR2","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/s12348-020-00202-6","volume":"10","author":"F Nicolela Susanna","year":"2020","unstructured":"Nicolela Susanna F, Pavesio C. A review of ocular adverse events of biological anti-TNF drugs. J Ophthalmic Inflamm Infect. 2020;10(1):11.","journal-title":"J Ophthalmic Inflamm Infect"},{"issue":"5","key":"2780_CR3","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1080\/14712598.2019.1595578","volume":"19","author":"S Touhami","year":"2019","unstructured":"Touhami S, Diwo E, Seve P, Trad S, Bielefeld P, Sene D, et al. Expert opinion on the use of biological therapy in non-infectious uveitis. Expert Opin Biol Ther. 2019;19(5):477\u201390.","journal-title":"Expert Opin Biol Ther"},{"key":"2780_CR4","doi-asserted-by":"publisher","first-page":"100967","DOI":"10.1016\/j.preteyeres.2021.100967","volume":"85","author":"JY Oh","year":"2021","unstructured":"Oh JY, Lee RH. Mesenchymal stromal cells for the treatment of ocular autoimmune diseases. Prog Retin Eye Res. 2021;85:100967.","journal-title":"Prog Retin Eye Res"},{"issue":"1","key":"2780_CR5","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1186\/s13287-021-02158-3","volume":"12","author":"C Yang","year":"2021","unstructured":"Yang C, Wu M, You M, Chen Y, Luo M, Chen Q. The therapeutic applications of mesenchymal stromal cells from human perinatal tissues in autoimmune diseases. Stem Cell Res Ther. 2021;12(1):103.","journal-title":"Stem Cell Res Ther"},{"issue":"6","key":"2780_CR6","doi-asserted-by":"publisher","first-page":"3143","DOI":"10.1167\/iovs.10-6334","volume":"52","author":"X Zhang","year":"2011","unstructured":"Zhang X, Ren X, Li G, Jiao C, Zhang L, Zhao S, et al. Mesenchymal stem cells ameliorate experimental autoimmune uveoretinitis by comprehensive modulation of systemic autoimmunity. Invest Ophthalmol Vis Sci. 2011;52(6):3143\u201352.","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"1","key":"2780_CR7","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1073\/pnas.1522905113","volume":"113","author":"JH Ko","year":"2016","unstructured":"Ko JH, Lee HJ, Jeong HJ, Kim MK, Wee WR, Yoon SO, et al. Mesenchymal stem\/stromal cells precondition lung monocytes\/macrophages to produce tolerance against allo- and autoimmunity in the eye. Proc Natl Acad Sci USA. 2016;113(1):158\u201363.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"7","key":"2780_CR8","doi-asserted-by":"publisher","first-page":"478","DOI":"10.2174\/1566524018666180207155614","volume":"17","author":"L Dong","year":"2018","unstructured":"Dong L, Chen X, Shao H, Bai L, Li X, Zhang X. Mesenchymal stem cells inhibited dendritic cells via the regulation of STAT1 and STAT6 phosphorylation in experimental autoimmune uveitis. Curr Mol Med. 2018;17(7):478\u201387.","journal-title":"Curr Mol Med"},{"issue":"2","key":"2780_CR9","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1167\/iovs.11-8211","volume":"53","author":"R Tasso","year":"2012","unstructured":"Tasso R, Ilengo C, Quarto R, Cancedda R, Caspi RR, Pennesi G. Mesenchymal stem cells induce functionally active T-regulatory lymphocytes in a paracrine fashion and ameliorate experimental autoimmune uveitis. Invest Ophthalmol Vis Sci. 2012;53(2):786\u201393.","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"1\u20132","key":"2780_CR10","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.bbrc.2017.10.097","volume":"494","author":"JH Ko","year":"2017","unstructured":"Ko JH, Lee HJ, Jeong HJ, Oh JY. Ly6C(hi) monocytes are required for mesenchymal stem\/stromal cell-induced immune tolerance in mice with experimental autoimmune uveitis. Biochem Biophys Res Commun. 2017;494(1\u20132):6\u201312.","journal-title":"Biochem Biophys Res Commun"},{"issue":"8","key":"2780_CR11","doi-asserted-by":"publisher","first-page":"1228","DOI":"10.1080\/09273948.2017.1343356","volume":"26","author":"Y Qin","year":"2018","unstructured":"Qin Y, Chan AM, Chang YL, Matynia A, Kouris NA, Kimbrel EA, et al. Human embryonic stem cell-derived mesenchymal stromal cells decrease the development of severe experimental autoimmune uveitis in B10.RIII mice. Ocul Immunol Inflamm. 2018;26(8):1228\u201336.","journal-title":"Ocul Immunol Inflamm"},{"key":"2780_CR12","doi-asserted-by":"publisher","first-page":"297","DOI":"10.3389\/fimmu.2012.00297","volume":"3","author":"E Eggenhofer","year":"2012","unstructured":"Eggenhofer E, Benseler V, Kroemer A, Popp FC, Geissler EK, Schlitt HJ, et al. Mesenchymal stem cells are short-lived and do not migrate beyond the lungs after intravenous infusion. Front Immunol. 2012;3:297.","journal-title":"Front Immunol"},{"issue":"1","key":"2780_CR13","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1161\/hc0102.101442","volume":"105","author":"C Toma","year":"2002","unstructured":"Toma C, Pittenger MF, Cahill KS, Byrne BJ, Kessler PD. Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart. Circulation. 2002;105(1):93\u20138.","journal-title":"Circulation"},{"issue":"4","key":"2780_CR14","doi-asserted-by":"publisher","first-page":"618","DOI":"10.3171\/2014.5.SPINE13992","volume":"21","author":"BJ Dlouhy","year":"2014","unstructured":"Dlouhy BJ, Awe O, Rao RC, Kirby PA, Hitchon PW. Autograft-derived spinal cord mass following olfactory mucosal cell transplantation in a spinal cord injury patient: case report. J Neurosurg Spine. 2014;21(4):618\u201322.","journal-title":"J Neurosurg Spine"},{"issue":"9411","key":"2780_CR15","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1016\/S0140-6736(04)15695-X","volume":"363","author":"PR Vulliet","year":"2004","unstructured":"Vulliet PR, Greeley M, Halloran SM, MacDonald KA, Kittleson MD. Intra-coronary arterial injection of mesenchymal stromal cells and microinfarction in dogs. Lancet. 2004;363(9411):783\u20134.","journal-title":"Lancet"},{"issue":"1","key":"2780_CR16","doi-asserted-by":"publisher","first-page":"1535750","DOI":"10.1080\/20013078.2018.1535750","volume":"7","author":"C Thery","year":"2018","unstructured":"Thery C, Witwer KW, Aikawa E, Alcaraz MJ, Anderson JD, Andriantsitohaina R, et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J Extracell Vesicles. 2018;7(1):1535750.","journal-title":"J Extracell Vesicles"},{"key":"2780_CR17","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1007\/978-1-4939-3584-0_7","volume":"1416","author":"M Gnecchi","year":"2016","unstructured":"Gnecchi M, Danieli P, Malpasso G, Ciuffreda MC. Paracrine mechanisms of mesenchymal stem cells in tissue repair. Methods Mol Biol. 2016;1416:123\u201346.","journal-title":"Methods Mol Biol"},{"issue":"7","key":"2780_CR18","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.3390\/jcm8071025","volume":"8","author":"Y Zhou","year":"2019","unstructured":"Zhou Y, Yamamoto Y, Xiao Z, Ochiya T. The immunomodulatory functions of mesenchymal stromal\/stem cells mediated via paracrine activity. J Clin Med. 2019;8(7):1025.","journal-title":"J Clin Med"},{"issue":"11","key":"2780_CR19","doi-asserted-by":"publisher","first-page":"1233","DOI":"10.1089\/scd.2013.0479","volume":"23","author":"B Zhang","year":"2014","unstructured":"Zhang B, Yin Y, Lai RC, Tan SS, Choo AB, Lim SK. Mesenchymal stem cells secrete immunologically active exosomes. Stem Cells Dev. 2014;23(11):1233\u201344.","journal-title":"Stem Cells Dev"},{"issue":"2","key":"2780_CR20","doi-asserted-by":"publisher","first-page":"1568","DOI":"10.3390\/molecules19021568","volume":"19","author":"Q Ge","year":"2014","unstructured":"Ge Q, Zhou Y, Lu J, Bai Y, Xie X, Lu Z. miRNA in plasma exosome is stable under different storage conditions. Molecules. 2014;19(2):1568\u201375.","journal-title":"Molecules"},{"key":"2780_CR21","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.canlet.2020.05.004","volume":"486","author":"M Chinnappan","year":"2020","unstructured":"Chinnappan M, Srivastava A, Amreddy N, Razaq M, Pareek V, Ahmed R, et al. Exosomes as drug delivery vehicle and contributor of resistance to anticancer drugs. Cancer Lett. 2020;486:18\u201328.","journal-title":"Cancer Lett"},{"issue":"1","key":"2780_CR22","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1016\/j.biotechadv.2017.12.010","volume":"36","author":"AA Farooqi","year":"2018","unstructured":"Farooqi AA, Desai NN, Qureshi MZ, Librelotto DRN, Gasparri ML, Bishayee A, et al. Exosome biogenesis, bioactivities and functions as new delivery systems of natural compounds. Biotechnol Adv. 2018;36(1):328\u201334.","journal-title":"Biotechnol Adv"},{"issue":"3","key":"2780_CR23","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1007\/s10266-018-0395-9","volume":"107","author":"K Ren","year":"2019","unstructured":"Ren K. Exosomes in perspective: a potential surrogate for stem cell therapy. Odontology. 2019;107(3):271\u201384.","journal-title":"Odontology"},{"issue":"1","key":"2780_CR24","doi-asserted-by":"publisher","first-page":"4323","DOI":"10.1038\/s41598-017-04559-y","volume":"7","author":"L Bai","year":"2017","unstructured":"Bai L, Shao H, Wang H, Zhang Z, Su C, Dong L, et al. Effects of mesenchymal stem cell-derived exosomes on experimental autoimmune uveitis. Sci Rep. 2017;7(1):4323.","journal-title":"Sci Rep"},{"issue":"4\u20135","key":"2780_CR25","first-page":"217","volume":"13","author":"A Nasef","year":"2007","unstructured":"Nasef A, Chapel A, Mazurier C, Bouchet S, Lopez M, Mathieu N, et al. Identification of IL-10 and TGF-beta transcripts involved in the inhibition of T-lymphocyte proliferation during cell contact with human mesenchymal stem cells. Gene Expr. 2007;13(4\u20135):217\u201326.","journal-title":"Gene Expr"},{"issue":"6","key":"2780_CR26","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1093\/intimm\/10.6.807","volume":"10","author":"LV Rizzo","year":"1998","unstructured":"Rizzo LV, Xu H, Chan CC, Wiggert B, Caspi RR. IL-10 has a protective role in experimental autoimmune uveoretinitis. Int Immunol. 1998;10(6):807\u201314.","journal-title":"Int Immunol"},{"issue":"10","key":"2780_CR27","doi-asserted-by":"publisher","first-page":"16786","DOI":"10.1002\/jcb.28937","volume":"120","author":"R Jian","year":"2019","unstructured":"Jian R, Yang M, Xu F. Lentiviral-mediated silencing of mast cell-expressed membrane protein 1 promotes angiogenesis of rats with cerebral ischemic stroke. J Cell Biochem. 2019;120(10):16786\u201397.","journal-title":"J Cell Biochem"},{"issue":"4","key":"2780_CR28","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","volume":"25","author":"KJ Livak","year":"2001","unstructured":"Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25(4):402\u20138.","journal-title":"Methods"},{"key":"2780_CR29","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1007\/978-1-60761-720-4_22","volume":"900","author":"RK Agarwal","year":"2012","unstructured":"Agarwal RK, Silver PB, Caspi RR. Rodent models of experimental autoimmune uveitis. Methods Mol Biol. 2012;900:443\u201369.","journal-title":"Methods Mol Biol"},{"issue":"2","key":"2780_CR30","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1158\/1541-7786.MCR-18-0891","volume":"17","author":"A Gonda","year":"2019","unstructured":"Gonda A, Kabagwira J, Senthil GN, Wall NR. Internalization of exosomes through receptor-mediated endocytosis. Mol Cancer Res. 2019;17(2):337\u201347.","journal-title":"Mol Cancer Res"},{"key":"2780_CR31","doi-asserted-by":"publisher","first-page":"149","DOI":"10.3389\/fcell.2020.00149","volume":"8","author":"A Gowen","year":"2020","unstructured":"Gowen A, Shahjin F, Chand S, Odegaard KE, Yelamanchili SV. Mesenchymal stem cell-derived extracellular vesicles: challenges in clinical applications. Front Cell Dev Biol. 2020;8:149.","journal-title":"Front Cell Dev Biol"},{"key":"2780_CR32","doi-asserted-by":"publisher","first-page":"8825771","DOI":"10.1155\/2020\/8825771","volume":"2020","author":"AG Zhao","year":"2020","unstructured":"Zhao AG, Shah K, Cromer B, Sumer H. Mesenchymal stem cell-derived extracellular vesicles and their therapeutic potential. Stem Cells Int. 2020;2020:8825771.","journal-title":"Stem Cells Int"},{"issue":"1","key":"2780_CR33","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1186\/s13287-020-02025-7","volume":"11","author":"Y Li","year":"2020","unstructured":"Li Y, Altemus J, Lightner AL. Mesenchymal stem cells and acellular products attenuate murine induced colitis. Stem Cell Res Ther. 2020;11(1):515.","journal-title":"Stem Cell Res Ther"},{"issue":"3","key":"2780_CR34","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1002\/stem.2759","volume":"36","author":"S Fujii","year":"2018","unstructured":"Fujii S, Miura Y, Fujishiro A, Shindo T, Shimazu Y, Hirai H, et al. Graft-versus-host disease amelioration by human bone marrow mesenchymal stromal\/stem cell-derived extracellular vesicles is associated with peripheral preservation of Naive T cell populations. Stem Cells. 2018;36(3):434\u201345.","journal-title":"Stem Cells"},{"issue":"5","key":"2780_CR35","doi-asserted-by":"publisher","first-page":"1399","DOI":"10.7150\/thno.21072","volume":"8","author":"S Cosenza","year":"2018","unstructured":"Cosenza S, Toupet K, Maumus M, Luz-Crawford P, Blanc-Brude O, Jorgensen C, et al. Mesenchymal stem cells-derived exosomes are more immunosuppressive than microparticles in inflammatory arthritis. Theranostics. 2018;8(5):1399\u2013410.","journal-title":"Theranostics"},{"issue":"5","key":"2780_CR36","doi-asserted-by":"publisher","first-page":"1214","DOI":"10.1016\/j.stemcr.2017.04.008","volume":"8","author":"T Shigemoto-Kuroda","year":"2017","unstructured":"Shigemoto-Kuroda T, Oh JY, Kim DK, Jeong HJ, Park SY, Lee HJ, et al. MSC-derived extracellular vesicles attenuate immune responses in two autoimmune murine models: type 1 diabetes and uveoretinitis. Stem Cell Reports. 2017;8(5):1214\u201325.","journal-title":"Stem Cell Reports"},{"issue":"5","key":"2780_CR37","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1177\/0271678X17708917","volume":"38","author":"L Otero-Ortega","year":"2018","unstructured":"Otero-Ortega L, de Frutos MCG, Laso-Garcia F, Rodriguez-Frutos B, Medina-Gutierrez E, Lopez JA, et al. Exosomes promote restoration after an experimental animal model of intracerebral hemorrhage. J Cereb Blood Flow Metab. 2018;38(5):767\u201379.","journal-title":"J Cereb Blood Flow Metab"},{"issue":"5","key":"2780_CR38","doi-asserted-by":"publisher","first-page":"1055","DOI":"10.3892\/ijmm.2014.1663","volume":"33","author":"C Grange","year":"2014","unstructured":"Grange C, Tapparo M, Bruno S, Chatterjee D, Quesenberry PJ, Tetta C, et al. Biodistribution of mesenchymal stem cell-derived extracellular vesicles in a model of acute kidney injury monitored by optical imaging. Int J Mol Med. 2014;33(5):1055\u201363.","journal-title":"Int J Mol Med"},{"issue":"2","key":"2780_CR39","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/S0009-9236(97)90065-5","volume":"62","author":"RD Huhn","year":"1997","unstructured":"Huhn RD, Radwanski E, Gallo J, Affrime MB, Sabo R, Gonyo G, et al. Pharmacodynamics of subcutaneous recombinant human interleukin-10 in healthy volunteers. Clin Pharmacol Ther. 1997;62(2):171\u201380.","journal-title":"Clin Pharmacol Ther"},{"issue":"7","key":"2780_CR40","doi-asserted-by":"publisher","first-page":"1761","DOI":"10.1021\/acs.accounts.9b00109","volume":"52","author":"OG de Jong","year":"2019","unstructured":"de Jong OG, Kooijmans SAA, Murphy DE, Jiang L, Evers MJW, Sluijter JPG, et al. Drug delivery with extracellular vesicles: from imagination to innovation. Acc Chem Res. 2019;52(7):1761\u201370.","journal-title":"Acc Chem Res"},{"key":"2780_CR41","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1016\/j.addr.2020.04.004","volume":"159","author":"OM Elsharkasy","year":"2020","unstructured":"Elsharkasy OM, Nordin JZ, Hagey DW, de Jong OG, Schiffelers RM, Andaloussi SE, et al. Extracellular vesicles as drug delivery systems: Why and how? Adv Drug Deliv Rev. 2020;159:332\u201343.","journal-title":"Adv Drug Deliv Rev"},{"issue":"7","key":"2780_CR42","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1016\/j.tibtech.2017.03.004","volume":"35","author":"NL Syn","year":"2017","unstructured":"Syn NL, Wang L, Chow EK, Lim CT, Goh BC. Exosomes in cancer nanomedicine and immunotherapy: prospects and challenges. Trends Biotechnol. 2017;35(7):665\u201376.","journal-title":"Trends Biotechnol"},{"issue":"33","key":"2780_CR43","doi-asserted-by":"publisher","first-page":"8521","DOI":"10.1016\/j.biomaterials.2013.07.102","volume":"34","author":"Q Peng","year":"2013","unstructured":"Peng Q, Zhang S, Yang Q, Zhang T, Wei XQ, Jiang L, et al. Preformed albumin corona, a protective coating for nanoparticles based drug delivery system. Biomaterials. 2013;34(33):8521\u201330.","journal-title":"Biomaterials"},{"issue":"2","key":"2780_CR44","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/j.jconrel.2007.11.009","volume":"126","author":"T Ishida","year":"2008","unstructured":"Ishida T, Kashima S, Kiwada H. The contribution of phagocytic activity of liver macrophages to the accelerated blood clearance (ABC) phenomenon of PEGylated liposomes in rats. J Control Release. 2008;126(2):162\u20135.","journal-title":"J Control Release"},{"issue":"1","key":"2780_CR45","first-page":"75","volume":"1846","author":"KB Johnsen","year":"2014","unstructured":"Johnsen KB, Gudbergsson JM, Skov MN, Pilgaard L, Moos T, Duroux M. A comprehensive overview of exosomes as drug delivery vehicles\u2014endogenous nanocarriers for targeted cancer therapy. Biochim Biophys Acta. 2014;1846(1):75\u201387.","journal-title":"Biochim Biophys Acta"},{"key":"2780_CR46","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.jconrel.2015.03.033","volume":"207","author":"MJ Haney","year":"2015","unstructured":"Haney MJ, Klyachko NL, Zhao Y, Gupta R, Plotnikova EG, He Z, et al. Exosomes as drug delivery vehicles for Parkinson\u2019s disease therapy. J Control Release. 2015;207:18\u201330.","journal-title":"J Control Release"},{"key":"2780_CR47","doi-asserted-by":"publisher","first-page":"6917","DOI":"10.2147\/IJN.S264498","volume":"15","author":"Y Zhang","year":"2020","unstructured":"Zhang Y, Bi J, Huang J, Tang Y, Du S, Li P. Exosome: a review of its classification, isolation techniques, storage, diagnostic and targeted therapy applications. Int J Nanomed. 2020;15:6917\u201334.","journal-title":"Int J Nanomed"},{"issue":"4","key":"2780_CR48","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1038\/nbt.1807","volume":"29","author":"L Alvarez-Erviti","year":"2011","unstructured":"Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, Wood MJ. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol. 2011;29(4):341\u20135.","journal-title":"Nat Biotechnol"},{"key":"2780_CR49","doi-asserted-by":"publisher","first-page":"34562","DOI":"10.1038\/srep34562","volume":"6","author":"B Yu","year":"2016","unstructured":"Yu B, Shao H, Su C, Jiang Y, Chen X, Bai L, et al. Exosomes derived from MSCs ameliorate retinal laser injury partially by inhibition of MCP-1. Sci Rep. 2016;6:34562.","journal-title":"Sci Rep"},{"issue":"1","key":"2780_CR50","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1021\/acs.molpharmaceut.8b00901","volume":"16","author":"CK Das","year":"2019","unstructured":"Das CK, Jena BC, Banerjee I, Das S, Parekh A, Bhutia SK, et al. Exosome as a novel shuttle for delivery of therapeutics across biological barriers. Mol Pharm. 2019;16(1):24\u201340.","journal-title":"Mol Pharm"},{"issue":"6","key":"2780_CR51","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1038\/ncb1596","volume":"9","author":"H Valadi","year":"2007","unstructured":"Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007;9(6):654\u20139.","journal-title":"Nat Cell Biol"},{"key":"2780_CR52","doi-asserted-by":"publisher","first-page":"105663","DOI":"10.1016\/j.intimp.2019.05.048","volume":"74","author":"L Guo","year":"2019","unstructured":"Guo L, Lai P, Wang Y, Huang T, Chen X, Luo C, et al. Extracellular vesicles from mesenchymal stem cells prevent contact hypersensitivity through the suppression of Tc1 and Th1 cells and expansion of regulatory T cells. Int Immunopharmacol. 2019;74:105663.","journal-title":"Int Immunopharmacol"},{"issue":"11","key":"2780_CR53","doi-asserted-by":"publisher","first-page":"9433","DOI":"10.1002\/jcb.27260","volume":"119","author":"S Nojehdehi","year":"2018","unstructured":"Nojehdehi S, Soudi S, Hesampour A, Rasouli S, Soleimani M, Hashemi SM. Immunomodulatory effects of mesenchymal stem cell-derived exosomes on experimental type-1 autoimmune diabetes. J Cell Biochem. 2018;119(11):9433\u201343.","journal-title":"J Cell Biochem"},{"issue":"5","key":"2780_CR54","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1007\/s12975-017-0599-2","volume":"9","author":"RL Webb","year":"2018","unstructured":"Webb RL, Kaiser EE, Scoville SL, Thompson TA, Fatima S, Pandya C, et al. Human neural stem cell extracellular vesicles improve tissue and functional recovery in the murine thromboembolic stroke model. Transl Stroke Res. 2018;9(5):530\u20139.","journal-title":"Transl Stroke Res"},{"issue":"2","key":"2780_CR55","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1007\/s00125-015-3808-0","volume":"59","author":"E Favaro","year":"2016","unstructured":"Favaro E, Carpanetto A, Caorsi C, Giovarelli M, Angelini C, Cavallo-Perin P, et al. Human mesenchymal stem cells and derived extracellular vesicles induce regulatory dendritic cells in type 1 diabetic patients. Diabetologia. 2016;59(2):325\u201333.","journal-title":"Diabetologia"},{"issue":"4","key":"2780_CR56","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1007\/s12026-016-8798-6","volume":"64","author":"W Chen","year":"2016","unstructured":"Chen W, Huang Y, Han J, Yu L, Li Y, Lu Z, et al. Immunomodulatory effects of mesenchymal stromal cells-derived exosome. Immunol Res. 2016;64(4):831\u201340.","journal-title":"Immunol Res"},{"issue":"11","key":"2780_CR57","doi-asserted-by":"publisher","first-page":"1374","DOI":"10.1089\/scd.2014.0563","volume":"24","author":"AVG de Andrade","year":"2015","unstructured":"de Andrade AVG, Bertolino G, Riewaldt J, Bieback K, Karbanova J, Odendahl M, et al. Extracellular vesicles secreted by bone marrow- and adipose tissue-derived mesenchymal stromal cells fail to suppress lymphocyte proliferation. Stem Cells Dev. 2015;24(11):1374\u20136.","journal-title":"Stem Cells Dev."},{"issue":"3","key":"2780_CR58","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1089\/scd.2018.0097","volume":"28","author":"SK Crain","year":"2019","unstructured":"Crain SK, Robinson SR, Thane KE, Davis AM, Meola DM, Barton BA, et al. Extracellular vesicles from Wharton\u2019s jelly mesenchymal stem cells suppress CD4 expressing T cells through transforming growth factor beta and adenosine signaling in a canine model. Stem Cells Dev. 2019;28(3):212\u201326.","journal-title":"Stem Cells Dev"},{"key":"2780_CR59","doi-asserted-by":"publisher","first-page":"556","DOI":"10.3389\/fimmu.2014.00556","volume":"5","author":"R Blazquez","year":"2014","unstructured":"Blazquez R, Sanchez-Margallo FM, de la Rosa O, Dalemans W, Alvarez V, Tarazona R, et al. Immunomodulatory potential of human adipose mesenchymal stem cells derived exosomes on in vitro stimulated T cells. Front Immunol. 2014;5:556.","journal-title":"Front Immunol"},{"issue":"2","key":"2780_CR60","doi-asserted-by":"publisher","first-page":"270","DOI":"10.7150\/thno.16154","volume":"7","author":"M Monguio-Tortajada","year":"2017","unstructured":"Monguio-Tortajada M, Roura S, Galvez-Monton C, Pujal JM, Aran G, Sanjurjo L, et al. Nanosized UCMSC-derived extracellular vesicles but not conditioned medium exclusively inhibit the inflammatory response of stimulated T cells: implications for nanomedicine. Theranostics. 2017;7(2):270\u201384.","journal-title":"Theranostics"},{"issue":"6","key":"2780_CR61","doi-asserted-by":"publisher","first-page":"6670","DOI":"10.1021\/acsnano.9b01004","volume":"13","author":"M Riazifar","year":"2019","unstructured":"Riazifar M, Mohammadi MR, Pone EJ, Yeri A, Lasser C, Segaliny AI, et al. Stem cell-derived exosomes as nanotherapeutics for autoimmune and neurodegenerative disorders. ACS Nano. 2019;13(6):6670\u201388.","journal-title":"ACS Nano"},{"key":"2780_CR62","doi-asserted-by":"publisher","first-page":"5356760","DOI":"10.1155\/2017\/5356760","volume":"2017","author":"F Mao","year":"2017","unstructured":"Mao F, Wu Y, Tang X, Kang J, Zhang B, Yan Y, et al. Exosomes derived from human umbilical cord mesenchymal stem cells relieve inflammatory bowel disease in mice. Biomed Res Int. 2017;2017:5356760.","journal-title":"Biomed Res Int"},{"issue":"9","key":"2780_CR63","doi-asserted-by":"publisher","first-page":"1747","DOI":"10.1007\/s00018-019-03035-2","volume":"76","author":"H Kahroba","year":"2019","unstructured":"Kahroba H, Hejazi MS, Samadi N. Exosomes: from carcinogenesis and metastasis to diagnosis and treatment of gastric cancer. Cell Mol Life Sci. 2019;76(9):1747\u201358.","journal-title":"Cell Mol Life Sci"},{"issue":"4","key":"2780_CR64","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1038\/nrm.2017.125","volume":"19","author":"G van Niel","year":"2018","unstructured":"van Niel G, D\u2019Angelo G, Raposo G. Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol. 2018;19(4):213\u201328.","journal-title":"Nat Rev Mol Cell Biol"}],"container-title":["Stem Cell Research &amp; Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13287-022-02780-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13287-022-02780-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13287-022-02780-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,11]],"date-time":"2022-11-11T02:04:50Z","timestamp":1668132290000},"score":1,"resource":{"primary":{"URL":"https:\/\/stemcellres.biomedcentral.com\/articles\/10.1186\/s13287-022-02780-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,7]]},"references-count":64,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["2780"],"URL":"https:\/\/doi.org\/10.1186\/s13287-022-02780-9","relation":{},"ISSN":["1757-6512"],"issn-type":[{"value":"1757-6512","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,7]]},"assertion":[{"value":"11 November 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 February 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 March 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The animal studies were approved by the Laboratory Animal Care and Use Committee of Tianjin Medical University Eye Hospital (TMUEC) (No. TJYY2019103022).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors have declared that no competing interest exists.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"100"}}