{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T06:52:43Z","timestamp":1781679163834,"version":"3.54.5"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002809","name":"Generalitat de Catalunya","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Spanish Ministry of Science and Innovation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014181","name":"Junta de Extremadura","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014181","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100023924","name":"Vocational Training","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100023924","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002701","name":"Ministry of Education","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002701","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:p>\n                    Effective immunosuppression in large animal models is essential for successful preclinical assessment of cell-based therapies in the allo- or xeno-transplantation setting. Pigs, due to their physiological and immunological similarity to humans, are widely used in translational research. However, direct, longitudinal comparisons of immunosuppressive strategies in swine are scarce, limiting the development of safe and reliable protocols. To address this gap, we performed a head-to-head comparison of two immunosuppressive regimens in pigs (\n                    <jats:italic>n<\/jats:italic>\n                    =\u202f8; 4 animals per group) to identify a protocol that achieves robust immune modulation with minimal systemic toxicity. Protocol I consisted of an intravenous induction with mycophenolate mofetil (MMF) and methylprednisolone, followed by oral MMF and tacrolimus. Protocol II included intravenous abatacept and methylprednisolone, two booster doses of abatacept, and daily oral cyclosporine A. Both regimens were administered for 6\u202fweeks, followed by a four-week recovery period. Statistical analyses included normality testing (Shapiro\u2013Wilk), multiple t-tests or Mann\u2013Whitney tests with false discovery rate correction for between-group comparisons, and two-way repeated measures ANOVA or mixed-effects models for longitudinal analysis. Both protocols induced lymphopenia without systemic toxicity but exhibited distinct immunological profiles. Protocol I promoted rapid and reversible lymphocyte suppression, whereas Protocol II induced a slower onset with sustained inhibitory signaling. Phenotypic analysis revealed dynamic shifts within lymphocyte populations, including a decline in the CD4\/CD8 ratio that did not reach statistical significance. CD21\n                    <jats:sup>+<\/jats:sup>\n                    lymphocytes were differentially affected: Protocol I maintained higher levels after an initial transient decrease, while Protocol II showed a progressive reduction with significant differences at multiple time points. These findings highlight that co-stimulation blockade combined with calcineurin inhibition enforces deeper functional suppression, whereas MMF\/tacrolimus-based therapy allows partial recovery of immune compartments. This direct comparative analysis provides a critical framework for designing targeted immunosuppressive strategies for translational models.\n                  <\/jats:p>","DOI":"10.3389\/fvets.2026.1816404","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T05:57:38Z","timestamp":1781675858000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A pilot study investigating the comparison of immunological responses to two immunosuppressive regimens in a porcine model"],"prefix":"10.3389","volume":"13","author":[{"given":"Mar\u00eda","family":"Pulido","sequence":"first","affiliation":[{"name":"Jesus Us\u00f3n Minimally Invasive Surgery Centre","place":["C\u00e1ceres, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"B\u00e1ez-D\u00edaz","sequence":"additional","affiliation":[{"name":"Jesus Us\u00f3n Minimally Invasive Surgery Centre","place":["C\u00e1ceres, Spain"]},{"name":"Banc de Sang i Teixits (BST), Musculoskeletal Tissue Engineering Group, Vall d'Hebron Research Institute (VHIR), Departament de Medicina, Universitat Aut\u00f2noma de Barcelona","place":["Barcelona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ver\u00f3nica","family":"\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Jesus Us\u00f3n Minimally Invasive Surgery Centre","place":["C\u00e1ceres, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F\u00e1tima","family":"V\u00e1zquez-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Jesus Us\u00f3n Minimally Invasive Surgery Centre","place":["C\u00e1ceres, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaquim","family":"Vives","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Program and Program for Clinical Translation of Regenerative Medicine in Catalonia-P-CMR[C], Bellvitge Institute for Biomedical Research (IDIBELL), Catalan Institution for Research and Advanced Studies (ICREA)","place":["Barcelona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angel","family":"Raya","sequence":"additional","affiliation":[{"name":"Biomedical Research Network Centre in Bioengineering, Nanomaterials, and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III","place":["Madrid, Spain"]},{"name":"Immunology Unit, Department of Physiology, Universidad de Extremadura","place":["C\u00e1ceres, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier G","family":"Casado","sequence":"additional","affiliation":[{"name":"Banc de Sang i Teixits (BST), Musculoskeletal Tissue Engineering Group, Vall d'Hebron Research Institute (VHIR), Departament de Medicina, Universitat Aut\u00f2noma de Barcelona","place":["Barcelona, Spain"]},{"name":"Institute of Molecular Pathology Biomarkers, Universidad de Extremadura","place":["C\u00e1ceres, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco Miguel","family":"S\u00e1nchez-Margallo","sequence":"additional","affiliation":[{"name":"Jesus Us\u00f3n Minimally Invasive Surgery Centre","place":["C\u00e1ceres, Spain"]},{"name":"Banc de Sang i Teixits (BST), Musculoskeletal Tissue Engineering Group, Vall d'Hebron Research Institute (VHIR), Departament de Medicina, Universitat Aut\u00f2noma de Barcelona","place":["Barcelona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ver\u00f3nica","family":"Cris\u00f3stomo","sequence":"additional","affiliation":[{"name":"Jesus Us\u00f3n Minimally Invasive Surgery Centre","place":["C\u00e1ceres, Spain"]},{"name":"Banc de Sang i Teixits (BST), Musculoskeletal Tissue Engineering Group, Vall d'Hebron Research Institute (VHIR), Departament de Medicina, Universitat Aut\u00f2noma de Barcelona","place":["Barcelona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"L\u00f3pez","sequence":"additional","affiliation":[{"name":"Jesus Us\u00f3n Minimally Invasive Surgery Centre","place":["C\u00e1ceres, Spain"]},{"name":"Banc de Sang i Teixits (BST), Musculoskeletal Tissue Engineering Group, Vall d'Hebron Research Institute (VHIR), Departament de Medicina, Universitat Aut\u00f2noma de Barcelona","place":["Barcelona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"ref1","first-page":"335","volume-title":"Adv Exp Med Biol","author":"Bergen","year":"2022"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1038\/laban.935","article-title":"Common swine models of cardiovascular disease for research and training","volume":"45","author":"Cris\u00f3stomo","year":"2016","journal-title":"Lab 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