{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T15:35:59Z","timestamp":1781796959519,"version":"3.54.5"},"reference-count":71,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2021,10,19]],"date-time":"2021-10-19T00:00:00Z","timestamp":1634601600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI19\/00245, RD16\/0011\/0002 and RD16\/0011\/0004"],"award-info":[{"award-number":["PI19\/00245, RD16\/0011\/0002 and RD16\/0011\/0004"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Agencia Valenciana de Innovaci\u00f3n","award":["INNVA1\/2021\/29"],"award-info":[{"award-number":["INNVA1\/2021\/29"]}]},{"name":"Conselleria de Innovaci\u00f3n, Universidades, Ciencia y Sociedad Digital","award":["ACIF\/2018\/254, ACIF\/2017\/318, ACIF\/2020\/352 and BEFPI\/2020\/042"],"award-info":[{"award-number":["ACIF\/2018\/254, ACIF\/2017\/318, ACIF\/2020\/352 and BEFPI\/2020\/042"]}]},{"name":"European Union through the Operational Program of the European Regional Development Fund (FEDER) of the Valencian Community","award":["2014-2020"],"award-info":[{"award-number":["2014-2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) have therapeutic potential in the treatment of several immune disorders, including ulcerative colitis, owing to their regenerative and immunosuppressive properties. We recently showed that MSCs engineered to overexpress hypoxia-inducible factor 1-alpha and telomerase (MSC-T-HIF) and conditioned with pro-inflammatory stimuli release EVs (EVMSC-T-HIFC) with potent immunomodulatory activity. We tested the efficacy of EVMSC-T-HIFC to repolarize M1 macrophages (M\u03c61) to M2-like macrophages (M\u03c62-like) by analyzing surface markers and cytokines and performing functional assays in co-culture, including efferocytosis and T-cell proliferation. We also studied the capacity of EVMSC-T-HIFC to dampen the inflammatory response of activated endothelium and modulate fibrosis. Finally, we tested the therapeutic capacity of EVMSC-T-HIFC in an acute colitis model. EVMSC-T-HIFc induced the repolarization of monocytes from M\u03c61 to an M\u03c62-like phenotype, which was accompanied by reduced inflammatory cytokine release. EVMSC-T-HIFc-treated M\u03c61 had similar effects of immunosuppression on activated peripheral blood mononuclear cells (PBMC) as M\u03c62, and reduced the adhesion of PBMCs to activated endothelium. EVMSC-T-HIFc also prevented myofibroblast differentiation of TGF-\u03b2-treated fibroblasts. Finally, administration of EVMSC-T-HIFc promoted healing in a TNBS-induced mouse colitis model in terms of preserving colon length and intestinal mucosa architecture and altering the ratio of M\u03c61\/ M\u03c62 infiltration. In conclusion, EVMSC-T-HIFC have effective anti-inflammatory properties, making them potential therapeutic agents in cell free-based therapies for the treatment of Crohn\u2019s disease and likely other immune-mediated inflammatory diseases.<\/jats:p>","DOI":"10.3390\/ijms222011269","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T03:01:13Z","timestamp":1634698873000},"page":"11269","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["HIF-Overexpression and Pro-Inflammatory Priming in Human Mesenchymal Stromal Cells Improves the Healing Properties of Extracellular Vesicles in Experimental Crohn\u2019s Disease"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7671-4734","authenticated-orcid":false,"given":"Marta","family":"G\u00f3mez-Ferrer","sequence":"first","affiliation":[{"name":"Regenerative Medicine and Heart Transplantation Unit, Instituto de Investigaci\u00f3n Sanitaria La Fe, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Amaro-Prellezo","sequence":"additional","affiliation":[{"name":"Regenerative Medicine and Heart Transplantation Unit, Instituto de Investigaci\u00f3n Sanitaria La Fe, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6141-8484","authenticated-orcid":false,"given":"Akaitz","family":"Dorronsoro","sequence":"additional","affiliation":[{"name":"Regenerative Medicine and Heart Transplantation Unit, Instituto de Investigaci\u00f3n Sanitaria La Fe, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"S\u00e1nchez-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Regenerative Medicine and Heart Transplantation Unit, Instituto de Investigaci\u00f3n Sanitaria La Fe, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9456-5541","authenticated-orcid":false,"given":"\u00c1ngeles","family":"Vicente","sequence":"additional","affiliation":[{"name":"Secci\u00f3n Departamental de Biolog\u00eda Celular, Facultad de Medicina, Universidad Complutense de Madrid, 28040 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria, Hospital Cl\u00ednico San Carlos, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas","family":"Cos\u00edn-Roger","sequence":"additional","affiliation":[{"name":"Hospital Dr Peset, FISABIO, 46017 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Dolores","family":"Barrachina","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Facultad de Medicina, University of Valencia, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Carmen","family":"Baquero","sequence":"additional","affiliation":[{"name":"Servicio de Cirug\u00eda Oral y Maxilofacial, Hospital Universitari I Polit\u00e8cnic La Fe, Avenida Fernando Abril Martorell, 106, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3112-5944","authenticated-orcid":false,"given":"Jaris","family":"Valencia","sequence":"additional","affiliation":[{"name":"Secci\u00f3n Departamental de Biolog\u00eda Celular, Facultad de Medicina, Universidad Complutense de Madrid, 28040 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria, Hospital Cl\u00ednico San Carlos, 28040 Madrid, 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