000148531 001__ 148531
000148531 005__ 20250120165541.0
000148531 0247_ $$2doi$$a10.1016/j.vetimm.2016.02.007
000148531 0248_ $$2sideral$$a93501
000148531 037__ $$aART-2016-93501
000148531 041__ $$aeng
000148531 100__ $$0(orcid)0000-0001-9818-508X$$aBarrachina, Laura$$uUniversidad de Zaragoza
000148531 245__ $$aEffect of inflammatory environment on equine bone marrow derived mesenchymal stem cells immunogenicity and immunomodulatory properties
000148531 260__ $$c2016
000148531 5060_ $$aAccess copy available to the general public$$fUnrestricted
000148531 5203_ $$aMesenchymal stem cells (MSCs) are being investigated for the treatment of equine joint diseases because of their regenerative potential. Recently, the focus mainly has addressed to their immunomodulatory capacities. Inflammation plays a central role in joint pathologies, since the release of proinflammatory mediators to the synovial fluid (SF) leads to the activation of enzymatic degradation of the cartilage. MSCs can modulate the local immune environment through direct or paracrine interaction with immune cells, suppressing their proliferation and re-addressing their functions. Proinflammatory molecules can induce MSC immunoregulatory potential, but they could also increase the expression of immunogenic molecules. Studying the effect of inflammatory environment on MSC immunomodulation and immunogenicity profiles is mandatory to improve cellular therapies. The aim of this study was to analyse the response of equine bone marrow MSCs (eBM-MSCs) to three inflammatory conditions. Equine BM-MSCs from three animals were exposed to: (a) 20% allogeneic inflammatory SF (SF); (b) 50 ng/ml of TNFa and IFN¿ (CK50) and (c) 20 ng/ml of TNFa and IFN¿ (CK20). After 72 h of exposure, expression of immunogenic and immunomodulation-related molecules, including cell-to-cell contact and paracrine signalling molecules, were analysed by RT-qPCR and flow cytometry. The gene expression of adhesion molecules was upregulated whereas MSC migration-related genes were downregulated by all inflammatory conditions tested. CK culture conditions significantly upregulated the expression of COX-2, iNOS, IDO and IL-6. MHC-I gene expression was upregulated by all conditions, whereas MHC-II was upregulated only after CK priming. The expression of CD40 did not significantly change, whereas the ligand, CD40L, was downregulated in CK conditions. Flow cytometry showed an increase in the percentage of positive cells and mean fluorescence intensity (MFI) of the MHC-I and MHC-II molecules at CK50 conditions, supporting the gene expression results. These outcomes reinforce the change of the immunophenotype of the eBM-MSCs according to the surrounding conditions. Inflammatory synovial environment did not lead to significant changes, so the environment found by eBM-MSCs when they are intraarticular administered may not be enough to activate their immunomodulatory potential. CK priming at tested doses enhances the immunoregulatory profile of eBM-MSCs, which may promote a therapeutic benefit. Even if CK priming induced an upregulation of MHC expression, costimulatory molecule expression however was not upregulated, suggesting that immunogenicity might not be increased. This study provides a better understanding about the behaviour of eBM-MSCs inside the inflamed joint and constitutes a first step to improve MSC-based therapies for equine joint diseases.
000148531 536__ $$9info:eu-repo/grantAgreement/ES/MICINN/AGL2011-28609
000148531 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
000148531 590__ $$a1.718$$b2016
000148531 591__ $$aVETERINARY SCIENCES$$b26 / 135 = 0.193$$c2016$$dQ1$$eT1
000148531 591__ $$aIMMUNOLOGY$$b125 / 149 = 0.839$$c2016$$dQ4$$eT3
000148531 592__ $$a0.741$$b2016
000148531 593__ $$aVeterinary (miscellaneous)$$c2016$$dQ1
000148531 593__ $$aImmunology$$c2016$$dQ3
000148531 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion
000148531 700__ $$0(orcid)0000-0002-1075-8267$$aRemacha, Ana Rosa$$uUniversidad de Zaragoza
000148531 700__ $$0(orcid)0000-0001-7188-0461$$aRomero, Antonio$$uUniversidad de Zaragoza
000148531 700__ $$0(orcid)0000-0002-8712-2275$$aVázquez, Francisco José$$uUniversidad de Zaragoza
000148531 700__ $$0(orcid)0000-0003-4489-3130$$aAlbareda, Jorge$$uUniversidad de Zaragoza
000148531 700__ $$aPrades, Marta
000148531 700__ $$0(orcid)0000-0002-4495-8857$$aRanera, Beatriz
000148531 700__ $$0(orcid)0000-0001-5740-0185$$aZaragoza, Pilar$$uUniversidad de Zaragoza
000148531 700__ $$0(orcid)0000-0001-6016-4726$$aMartín-Burriel, Inmaculada$$uUniversidad de Zaragoza
000148531 700__ $$0(orcid)0000-0003-3289-2675$$aRodellar, Clementina$$uUniversidad de Zaragoza
000148531 7102_ $$11001$$2420$$aUniversidad de Zaragoza$$bDpto. Anatom.,Embri.Genét.Ani.$$cÁrea Genética
000148531 7102_ $$11004$$2830$$aUniversidad de Zaragoza$$bDpto. Cirugía,Ginecol.Obstetr.$$cÁrea Traumatología y Ortopedia
000148531 7102_ $$11009$$2617$$aUniversidad de Zaragoza$$bDpto. Patología Animal$$cÁrea Medicina y Cirugía Animal
000148531 773__ $$g171 (2016), 57-65$$pVet. immunol. immunopathol.$$tVETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY$$x0165-2427
000148531 8564_ $$s423902$$uhttps://zaguan.unizar.es/record/148531/files/texto_completo.pdf$$yPostprint
000148531 8564_ $$s1138414$$uhttps://zaguan.unizar.es/record/148531/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint
000148531 909CO $$ooai:zaguan.unizar.es:148531$$particulos$$pdriver
000148531 951__ $$a2025-01-20-14:52:28
000148531 980__ $$aARTICLE