{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T02:21:26Z","timestamp":1775874086051,"version":"3.50.1"},"reference-count":82,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal intestinal tract and has characteristic hypertrophic adipose changes observed in the mesentery. To better understand the role of the mesentery in the pathophysiology of Crohn's disease (CD), we evaluated the immunomodulatory potential of mesenchymal stem cells (MSCs) and their secreted extracellular vesicles (EVs) derived from Crohn's patients. MSCs and EVs were isolated from the mesentery and subcutaneous tissues of CD patients and healthy individuals subcutaneous tissues, and were analysed for differentiation, cytokine expression, self\u2010renewal and proliferation. The varying capacity of these tissue\u2010derived MSCs and EVs to attenuate T\u2010cell activation was measured in in vitro and an in vivo murine model. RNA sequencing of inflamed Crohn's disease mesentery tissue revealed an enrichment of T\u2010cell activation compared to non\u2010inflamed subcutaneous tissue. MSCs and MSC\u2010derived EVs isolated from Crohn's mesentery lose their ability to attenuate DSS\u2010induced colitis compared to subcutaneous tissue\u2010derived cell or EV therapy. We found that treatment with subcutaneous isolated MSCs and their EV product compared to Crohn's mesentery MSCs or EVs, the inhibition of T\u2010cell proliferation and IFN\u2010\u03b3, IL\u201017a production increased, suggesting a non\u2010inflamed microenvironment allows for T\u2010cell inhibition by MSCs\/EVs. Our results demonstrate that Crohn's patient\u2010derived diseased mesentery tissue MSCs lose their immunosuppressive capacity in the treatment of colitis by distinct regulation of pathogenic T\u2010cell responses and\/or T\u2010cell infiltration into the colon.<\/jats:p>","DOI":"10.1111\/jcmm.17483","type":"journal-article","created":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T09:40:54Z","timestamp":1662025254000},"page":"4924-4939","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Effect of Crohn's disease mesenteric mesenchymal stem cells and their extracellular vesicles on T\u2010cell immunosuppressive capacity"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3220-7148","authenticated-orcid":false,"given":"Neda","family":"Dadgar","sequence":"first","affiliation":[{"name":"Department of Colorectal Surgery Digestive Disease Surgical Institute  Cleveland Ohio USA"},{"name":"Department of Inflammation and Immunity Lerner Research Institute  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Altemus","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Immunity Lerner Research Institute  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery Digestive Disease Surgical Institute  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy L.","family":"Lightner","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery Digestive Disease Surgical Institute  Cleveland Ohio USA"},{"name":"Department of Inflammation and Immunity Lerner Research Institute  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,9]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00462"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.09.009"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjx187"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/5173732"},{"issue":"3","key":"e_1_2_12_6_1","first-page":"154","article-title":"Biological properties of mesenchymal stem cells from different sources","volume":"2","author":"Via AG","year":"2012","journal-title":"Muscles Ligaments Tendons J"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-018-1750-x"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcyt.2016.03.291"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tec.2015.0017"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.3727\/096368912X657990"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.2337\/db10-0136"},{"issue":"3","key":"e_1_2_12_12_1","first-page":"110","article-title":"Isolation of mesenchymal stem cells from bone marrow wastes of spinal fusion procedure (TLIF) for low back pain patients and preparation of bone dusts for transplantable autologous bone graft with a serum glue","volume":"4","author":"Ichiyanagi T","year":"2010","journal-title":"Biosci Trends"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/14653240802398845"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22063023"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.30756"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izab151"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2009.104"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/scrt2"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01212"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23031854"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/iub.2385"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/brv.12608"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjaa179"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2005.10.027"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2007.0220"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.2006.0340"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-03-420612"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2016.05.055"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2016.142"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2019.08.033"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.2174\/13816128113199990416"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(98)70381-6"},{"issue":"3","key":"e_1_2_12_33_1","first-page":"253","article-title":"Inflammatory bowel disease. Considerations of etiology and pathogenesis","volume":"69","author":"Kirsner JB","year":"1978","journal-title":"Am J Gastroenterol"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02239143"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-5699(97)01000-1"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.32.4.403"},{"issue":"2","key":"e_1_2_12_37_1","first-page":"S1","article-title":"Auto\u2010immunity, allergy and inflammation","volume":"135","year":"2015","journal-title":"J Invest Dermatol"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1106442"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v23.i33.6016"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/718617"},{"key":"e_1_2_12_41_1","unstructured":"RachmilewitzD KarmeliF TakabayashiK RazE.Amelioration of experimental colitis by probiotics is due to the immunostimulatory effects of its DNA. 2002. WB Saunders Co independence square west curtis center STE 300 Philadelphia\u2026. p A398\u2010A398."},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1254"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1615253114"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.11-8008"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1500139"},{"key":"e_1_2_12_46_1","first-page":"55","article-title":"Isolation, characterization, differentiation, and application of adipose\u2010derived stem cells","volume":"123","author":"Kuhbier JW","year":"2010","journal-title":"Adv Biochem Eng Biotechnol"},{"issue":"1","key":"e_1_2_12_47_1","first-page":"140","article-title":"Comparative characterization of mesenchymal stem cells from human umbilical cord tissue and bone marrow","volume":"16","author":"Lu LL","year":"2008","journal-title":"Zhongguo Shi Yan Xue Ye Xue Za Zhi"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4652(199603)166:3<585::AID-JCP13>3.0.CO;2-6"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/83.11.775"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.10.3838"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2018.00639"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjz090"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0192949"},{"issue":"6","key":"e_1_2_12_54_1","first-page":"1085","article-title":"Evidence of IL\u201017 producing innate lymphoid cells in peripheral blood from patients with enteropathic spondyloarthritis","volume":"34","author":"Triggianese P","year":"2016","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.4252\/wjsc.v11.i9.618"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.26765"},{"issue":"1","key":"e_1_2_12_57_1","first-page":"108","article-title":"Differentiation potential of human mesenchymal stem cells derived from adipose tissue and bone marrow to sinus node\u2010like cells","volume":"5","author":"Yang J","year":"2012","journal-title":"Mol Med Rep"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/216806"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00694"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1102942"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v17.i4.459"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1132"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2015.327"},{"issue":"1","key":"e_1_2_12_64_1","first-page":"1","article-title":"Immunomodulatory effects of mesenchymal stem cells in peripheral nerve injury","volume":"13","author":"Li X","year":"2022","journal-title":"Stem Cell Research & Therapy"},{"key":"e_1_2_12_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep26851"},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01191"},{"key":"e_1_2_12_67_1","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0000000000000714"},{"key":"e_1_2_12_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11582"},{"key":"e_1_2_12_69_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.02.016"},{"key":"e_1_2_12_70_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.157.3.1261"},{"key":"e_1_2_12_71_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.2575"},{"key":"e_1_2_12_72_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.00651"},{"key":"e_1_2_12_73_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-019-1152-x"},{"key":"e_1_2_12_74_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-016-0363-7"},{"key":"e_1_2_12_75_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0121534"},{"key":"e_1_2_12_76_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.001720"},{"key":"e_1_2_12_77_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.112.114173"},{"key":"e_1_2_12_78_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.24486"},{"key":"e_1_2_12_79_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12015-016-9677-1"},{"key":"e_1_2_12_80_1","doi-asserted-by":"publisher","DOI":"10.1111\/boc.201400081"},{"key":"e_1_2_12_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2016.09.016"},{"key":"e_1_2_12_82_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2017.12"},{"key":"e_1_2_12_83_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.2564"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.17483","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jcmm.17483","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.17483","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T10:22:51Z","timestamp":1692440571000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.17483"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9]]},"references-count":82,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2022,10]]}},"alternative-id":["10.1111\/jcmm.17483"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.17483","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"value":"1582-1838","type":"print"},{"value":"1582-4934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9]]},"assertion":[{"value":"2022-04-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}