000087835 001__ 87835 000087835 005__ 20240104111813.0 000087835 0247_ $$2doi$$a10.1186/s13287-020-1571-8 000087835 0248_ $$2sideral$$a116252 000087835 037__ $$aART-2020-116252 000087835 041__ $$aeng 000087835 100__ $$0(orcid)0000-0001-9818-508X$$aBarrachina Porcar, Laura$$uUniversidad de Zaragoza 000087835 245__ $$aAllo-antibody production after intraarticular administration of mesenchymal stem cells (MSCs) in an equine osteoarthritis model: effect of repeated administration, MSC inflammatory stimulation, and equine leukocyte antigen (ELA) compatibility 000087835 260__ $$c2020 000087835 5060_ $$aAccess copy available to the general public$$fUnrestricted 000087835 5203_ $$aBackground Antibody production after allogeneic administration of mesenchymal stem cells (MSCs) could impact their clinical application. Proinflammatory priming of MSCs can potentiate their regulatory ability in vivo but increased expression of major histocompatibility complex (MHC) might augment their immunogenicity, potentially leading to immune memory thus limiting repeated allogeneic administration. This study aimed at evaluating the production of cytotoxic allo-antibodies directed against donor’s ELA (equine leukocyte antigen) in mismatched and halfmatched horses receiving repeated intraarticular administration of stimulated MSCs (MSC-primed) and unstimulated MSCs (MSC-naïve) in pathologic joints. Methods From available stored samples from a previous in vivo study, cells from one donor and serially collected sera (five time-points) from three groups of recipients were used based on their ELA haplotypes to perform microcytotoxicity assays: Group 1 recipients mismatched with the donor that received MSC-naïve (naïve-mismatched recipients); Group 2 recipients mismatched with the donor that received MSC-primed (primed-mismatched recipients); Group 3 recipients halfmatched with the donor (sharing 1/2 haplotypes) that received MSC-primed (primed-halfmatched recipients). Sera from recipients (neat, 1:2 and 1:16 dilution) were tested against target cells from the donor (cryopreserved and expanded MSC-naïve and MSC-primed) or from one animal presenting the same ELA haplotypes than the donor (fresh peripheral blood lymphocytes as control). Results One to three weeks after first MSC administration, all recipient groups produced allo-antibodies regardless of MSC received (naïve or primed) and matching degree with donor. However, secondary response after MSC re-exposure was less evident in halfmatched recipients (MSC-primed) than in mismatched ones (both MSC-naïve and MSC-primed). Recipients of MSC-primed (both mismatched and halfmatched) tended towards developing lower antibody response than MSC-naïve recipients in vivo, but MSC-primed were targeted to death in higher percentage in vitro in the microcytoxicity assay. Conclusions After first intraarticular allogeneic administration, the immunomodulatory profile of MSC-primed would have led to lower antibody production, but these antibodies would target more easily MSC-primed after second injection (re-exposure), likely because of their higher MHC expression. 000087835 536__ $$9info:eu-repo/grantAgreement/ES/DGA/A19-17R$$9info:eu-repo/grantAgreement/ES/MINECO/AGL2017-84411-P 000087835 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/ 000087835 590__ $$a6.832$$b2020 000087835 591__ $$aCELL & TISSUE ENGINEERING$$b7 / 29 = 0.241$$c2020$$dQ1$$eT1 000087835 591__ $$aMEDICINE, RESEARCH & EXPERIMENTAL$$b24 / 140 = 0.171$$c2020$$dQ1$$eT1 000087835 591__ $$aCELL BIOLOGY$$b45 / 195 = 0.231$$c2020$$dQ1$$eT1 000087835 592__ $$a1.599$$b2020 000087835 593__ $$aBiochemistry, Genetics and Molecular Biology (miscellaneous)$$c2020$$dQ1 000087835 593__ $$aMolecular Medicine$$c2020$$dQ1 000087835 593__ $$aMedicine (miscellaneous)$$c2020$$dQ1 000087835 593__ $$aCell Biology$$c2020$$dQ1 000087835 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion 000087835 700__ $$0(orcid)0000-0002-1481-9805$$aCequier Soler, Alina$$uUniversidad de Zaragoza 000087835 700__ $$0(orcid)0000-0001-7188-0461$$aRomero Lasheras, Antonio$$uUniversidad de Zaragoza 000087835 700__ $$0(orcid)0000-0003-1286-4968$$aVitoria Moraiz, Arantza$$uUniversidad de Zaragoza 000087835 700__ $$0(orcid)0000-0001-5740-0185$$aZaragoza Fernández, Pilar$$uUniversidad de Zaragoza 000087835 700__ $$0(orcid)0000-0002-8712-2275$$aVázquez Bringas, Francisco José$$uUniversidad de Zaragoza 000087835 700__ $$0(orcid)0000-0003-3289-2675$$aRodellar Penella, Clementina$$uUniversidad de Zaragoza 000087835 7102_ $$11001$$2420$$aUniversidad de Zaragoza$$bDpto. Anatom.,Embri.Genét.Ani.$$cÁrea Genética 000087835 7102_ $$11009$$2617$$aUniversidad de Zaragoza$$bDpto. Patología Animal$$cÁrea Medicina y Cirugía Animal 000087835 773__ $$g11 (2020), 52 [12 pp.]$$pStem cell res. ther.$$tStem cell research & therapy$$x1757-6512 000087835 8564_ $$s904822$$uhttps://zaguan.unizar.es/record/87835/files/texto_completo.pdf$$yVersión publicada 000087835 8564_ $$s48165$$uhttps://zaguan.unizar.es/record/87835/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000087835 909CO $$ooai:zaguan.unizar.es:87835$$particulos$$pdriver 000087835 951__ $$a2024-01-04-11:03:34 000087835 980__ $$aARTICLE