{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T04:38:01Z","timestamp":1789447081268,"version":"build-2803163510"},"reference-count":56,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,4,4]],"date-time":"2016-04-04T00:00:00Z","timestamp":1459728000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["279174 EC"],"award-info":[{"award-number":["279174 EC"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Modulation of innate immune responses in rheumatoid arthritis and other immune\u2010mediated disorders is of critical importance in the clinic since a growing body of information has shown the key contribution of dysregulated innate responses in the progression of the disease. Mesenchymal stromal cells (MSCs) are the focus of intensive efforts worldwide due to their key role in tissue regeneration and modulation of inflammation. In this study, we define innate immune responses occurring during the early course of treatment with a single dose of expanded adipose\u2010derived MSCs (eASCs) in established collagen\u2010induced arthritis. eASCs delay the progression of the disease during the early phase of the disease. This is accompanied by a transient induction of Ly6C<jats:sup>+<\/jats:sup> monocytes that differentiate into IL10<jats:sup>+<\/jats:sup>F4\/80<jats:sup>+<\/jats:sup> cells in arthritic mice. Strikingly, the induced IL10<jats:sup>+<\/jats:sup>F4\/80<jats:sup>+<\/jats:sup> myeloid cells preferentially accumulated in the draining lymph nodes. This effect was accompanied with a concomitant declining of their frequencies in the spleens. Our results show that eASCs attenuate the arthritic process by inducing an early innate cell signature that involves a transient induction of Ly6C<jats:sup>+<\/jats:sup> monocytes in periphery that differentiate into IL10<jats:sup>+<\/jats:sup>F4\/80<jats:sup>+<\/jats:sup> macrophages. Our findings demonstrate that early regulatory innate cell responses, involving the monocyte compartment, are targeted by the eASCs during the onset of collagen\u2010induced inflammation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/iid3.106","type":"journal-article","created":{"date-parts":[[2016,4,4]],"date-time":"2016-04-04T09:07:47Z","timestamp":1459760867000},"page":"213-224","source":"Crossref","is-referenced-by-count":25,"title":["Adipose\u2010derived mesenchymal stromal cells modulate experimental autoimmune arthritis by inducing an early regulatory innate cell signature"],"prefix":"10.1002","volume":"4","author":[{"given":"Mercedes","family":"Lopez\u2010Santalla","sequence":"first","affiliation":[{"name":"Hematopoietic Innovative Therapies Division Centro de Investigaciones Energ\u00e9ticas, Medioambientales y Tecnol\u00f3gicas (CIEMAT) and Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBER\u2010ER) Madrid Spain"},{"name":"Advanced Therapy Unit Centro de Investigaciones Energ\u00e9ticas, Medioambientales y Tecnol\u00f3gicas (CIEMAT) and Instituto de Investigaci\u00f3n Sanitaria Fundaci\u00f3n Jim\u00e9nez D\u00edaz (IIS\u2010FJD, UAM) Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramon","family":"Menta","sequence":"additional","affiliation":[{"name":"TiGenix SAU Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Manche\u00f1o\u2010Corvo","sequence":"additional","affiliation":[{"name":"TiGenix SAU Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Lopez\u2010Belmonte","sequence":"additional","affiliation":[{"name":"FARMACROS Albacete Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"DelaRosa","sequence":"additional","affiliation":[{"name":"TiGenix SAU Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan A.","family":"Bueren","sequence":"additional","affiliation":[{"name":"Hematopoietic Innovative Therapies Division Centro de Investigaciones Energ\u00e9ticas, Medioambientales y Tecnol\u00f3gicas (CIEMAT) and Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBER\u2010ER) Madrid Spain"},{"name":"Advanced Therapy Unit Centro de Investigaciones Energ\u00e9ticas, Medioambientales y Tecnol\u00f3gicas (CIEMAT) and Instituto de Investigaci\u00f3n Sanitaria Fundaci\u00f3n Jim\u00e9nez D\u00edaz (IIS\u2010FJD, UAM) Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilfried","family":"Dalemans","sequence":"additional","affiliation":[{"name":"TiGenix NV Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleuterio","family":"Lombardo","sequence":"additional","affiliation":[{"name":"TiGenix SAU Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina I.","family":"Garin","sequence":"additional","affiliation":[{"name":"Hematopoietic Innovative Therapies Division Centro de Investigaciones Energ\u00e9ticas, Medioambientales y Tecnol\u00f3gicas (CIEMAT) and Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBER\u2010ER) Madrid Spain"},{"name":"Advanced Therapy Unit Centro de Investigaciones Energ\u00e9ticas, Medioambientales y Tecnol\u00f3gicas (CIEMAT) and Instituto de Investigaci\u00f3n Sanitaria Fundaci\u00f3n Jim\u00e9nez D\u00edaz (IIS\u2010FJD, UAM) Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,4,4]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1004965"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2012.23"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.3109\/03009742.2012.716450"},{"key":"e_1_2_7_5_1","first-page":"1","article-title":"Myeloid\u2010derived suppressor cells have a proinflammatory role in the pathogenesis of autoimmune arthritis","author":"Guo C.","year":"2014","journal-title":"Ann. Rheum. Dis"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2015.02.001"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1203535"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-013-9783-z"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201444799"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2506"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/274314"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2013.168"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.132639"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2013.0023"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2011-200985"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.berh.2014.10.023"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.141804"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2009.123463"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.3727\/096368911X582769c"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-015-1040-9"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2010.09.009"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.4252\/wjsc.v6.i5.526"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204147"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.24405"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2008.101881"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.2113"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0897.2011.01069.x"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12015-014-9562-8"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2008.168534"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1905"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24162"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2013.093864"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1401776"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1402139"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1400857"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2012-302152"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39069"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2011.08.014"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.22511"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.08.026"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.10.004"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1109"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-201703"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-202450"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204816"},{"key":"e_1_2_7_46_1","first-page":"1","article-title":"Preclinical characterisation of the GM\u2010CSF receptor as a therapeutic target in rheumatoid arthritis","author":"Greven D. E.","year":"2014","journal-title":"Ann. Rheum. Dis"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0114962"},{"key":"e_1_2_7_48_1","first-page":"148","article-title":"The life and fate of mesenchymal stem cells","volume":"19","author":"Eggenhofer E.","year":"2014","journal-title":"Front Immunol"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1432"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-11-317321"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-07-2921"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.3727\/096368909X479677"},{"key":"e_1_2_7_53_1","first-page":"297","article-title":"Mesenchymal stem cells are short\u2010lived and do not migrate beyond the lungs after intravenous infusion","volume":"26","author":"Eggenhofer E.","year":"2012","journal-title":"Front Immunol"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2013.06.006"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2013.090092"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-202990"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.30326"}],"container-title":["Immunity, Inflammation and Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fiid3.106","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fiid3.106","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/iid3.106","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/iid3.106","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/iid3.106","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T15:22:14Z","timestamp":1694359334000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/iid3.106"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,4,4]]},"references-count":56,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2016,6]]}},"alternative-id":["10.1002\/iid3.106"],"URL":"https:\/\/doi.org\/10.1002\/iid3.106","archive":["Portico"],"relation":{},"ISSN":["2050-4527","2050-4527"],"issn-type":[{"value":"2050-4527","type":"print"},{"value":"2050-4527","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,4,4]]}}}