000074944 001__ 74944 000074944 005__ 20240104111812.0 000074944 0247_ $$2doi$$a10.1186/s12917-018-1556-3 000074944 0248_ $$2sideral$$a107712 000074944 037__ $$aART-2018-107712 000074944 041__ $$aeng 000074944 100__ $$0(orcid)0000-0001-9818-508X$$aBarrachina, L.$$uUniversidad de Zaragoza 000074944 245__ $$aAssessment of effectiveness and safety of repeat administration of proinflammatory primed allogeneic mesenchymal stem cells in an equine model of chemically induced osteoarthritis 000074944 260__ $$c2018 000074944 5060_ $$aAccess copy available to the general public$$fUnrestricted 000074944 5203_ $$aBackground: This study aimed at assessing the effectiveness and safety of repeated administrations of allogeneic bone marrow-derived mesenchymal stem cells (BM-MSCs) primed with tumor necrosis factor (TNF)-a and interferon-¿ in an equine model of chemically-induced osteoarthritis. Arthritis was induced in both radio-carpal (RC)-joints by amphotericin-B in 18 ponies, divided into three groups depending on the treatment injected: MSC-naïve (n=7), MSC-primed (n=7) and control (n=4). The study consisted of two phases and used one RC-joint of each animal in each phase, with four months time-lapse, in order to assess two end-points. Clinical, synovial, radiological and ultrasonographic follow-up was performed. At six months, animals were euthanized and both carpi were assessed by magnetic resonance imaging (MRI), gross anatomy, histopathology, histochemistry and gene expression. Results: Clinical and synovial inflammatory signs were quicker reduced in MSC-treated groups and repeated allogeneic administration did not produce adverse reactions, but MSC-primed group showed slight and transient local inflammation after second injection. Radiology and MRI did not show significant differences between treated and control groups, whereas ultrasonography suggested reduced synovial effusion in MSC-treated groups. Both MSC-treated groups showed enhanced cartilage gross appearance at two compared to six months (MSC-naïve, p<0.05). Cartilage histopathology did not reveal differences but histochemistry suggested delayed progression of proteoglycan loss in MSC-treated groups. Synovium histopathology indicated decreased inflammation (p<0.01) in MSC-primed and MSC-naïve at two and six months, respectively. At two months, cartilage from MSC-primed group significantly (p<0.05) upregulated collagen type II (COL2A1) and transforming growth factor (TGF)-ß1 and downregulated cyclooxygenase-2 and interleukin (IL)-1ß. At six months, MSC-treatments significantly downregulated TNFa (p<0.05), plus MSC-primed upregulated (p<0.05) COL2A1, aggrecan, cartilage oligomeric protein, tissue inhibitor of metalloproteinases-2 and TGF-ß1. In synovium, both MSC-treatments decreased (p<0.01) matrix metalloproteinase-13 expression at two months and MSC-primed also downregulated TNFa (p<0.05) and IL-1ß (p<0.01). Conclusions: Both MSC-treatments provided beneficial effects, mostly observed at short-term. Despite no huge differences between MSC-treatments, the findings suggested enhanced anti-inflammatory and regulatory potential of MSC-primed. While further research is needed to better understand these effects and clarify immunogenicity implications, these findings contribute to enlarge the knowledge about MSC therapeutics and how they could be influenced. 000074944 536__ $$9info:eu-repo/grantAgreement/ES/DGA/LAGENBIO-GROUP$$9info:eu-repo/grantAgreement/ES/MINECO/AGL2011-28609 000074944 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/ 000074944 590__ $$a1.792$$b2018 000074944 591__ $$aVETERINARY SCIENCES$$b33 / 141 = 0.234$$c2018$$dQ1$$eT1 000074944 592__ $$a0.848$$b2018 000074944 593__ $$aVeterinary (miscellaneous)$$c2018$$dQ1 000074944 593__ $$aMedicine (miscellaneous)$$c2018$$dQ1 000074944 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion 000074944 700__ $$0(orcid)0000-0002-1075-8267$$aRemacha, A.R.$$uUniversidad de Zaragoza 000074944 700__ $$0(orcid)0000-0001-7188-0461$$aRomero, A.$$uUniversidad de Zaragoza 000074944 700__ $$0(orcid)0000-0003-1286-4968$$aVitoria, A.$$uUniversidad de Zaragoza 000074944 700__ $$0(orcid)0000-0003-4489-3130$$aAlbareda, J.$$uUniversidad de Zaragoza 000074944 700__ $$0(orcid)0000-0003-2713-9232$$aPrades, M. 000074944 700__ $$aRoca, M. 000074944 700__ $$0(orcid)0000-0001-5740-0185$$aZaragoza, P.$$uUniversidad de Zaragoza 000074944 700__ $$0(orcid)0000-0002-8712-2275$$aVázquez, F.J.$$uUniversidad de Zaragoza 000074944 700__ $$0(orcid)0000-0003-3289-2675$$aRodellar, C.$$uUniversidad de Zaragoza 000074944 7102_ $$11001$$2420$$aUniversidad de Zaragoza$$bDpto. Anatom.,Embri.Genét.Ani.$$cÁrea Genética 000074944 7102_ $$11004$$2830$$aUniversidad de Zaragoza$$bDpto. Cirugía,Ginecol.Obstetr.$$cÁrea Traumatología y Ortopedia 000074944 7102_ $$11009$$2617$$aUniversidad de Zaragoza$$bDpto. Patología Animal$$cÁrea Medicina y Cirugía Animal 000074944 773__ $$g14, 1 (2018), 241 [17 pp]$$pBMC Vet. Res.$$tBMC VETERINARY RESEARCH$$x1746-6148 000074944 8564_ $$s6046013$$uhttps://zaguan.unizar.es/record/74944/files/texto_completo.pdf$$yVersión publicada 000074944 8564_ $$s92487$$uhttps://zaguan.unizar.es/record/74944/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000074944 909CO $$ooai:zaguan.unizar.es:74944$$particulos$$pdriver 000074944 951__ $$a2024-01-04-11:02:54 000074944 980__ $$aARTICLE