{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T18:28:04Z","timestamp":1788632884028,"version":"build-2803163510"},"reference-count":52,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,9]],"date-time":"2025-07-09T00:00:00Z","timestamp":1752019200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health","award":["SG-2019-12368961"],"award-info":[{"award-number":["SG-2019-12368961"]}]},{"name":"Italian Ministry of Health","award":["1731651"],"award-info":[{"award-number":["1731651"]}]},{"name":"Italian Ministry of Health","award":["DSB.AD008.795"],"award-info":[{"award-number":["DSB.AD008.795"]}]},{"name":"Fondazione Regionale per la Ricerca Biomedica (Regione Lombardia)","award":["SG-2019-12368961"],"award-info":[{"award-number":["SG-2019-12368961"]}]},{"name":"Fondazione Regionale per la Ricerca Biomedica (Regione Lombardia)","award":["1731651"],"award-info":[{"award-number":["1731651"]}]},{"name":"Fondazione Regionale per la Ricerca Biomedica (Regione Lombardia)","award":["DSB.AD008.795"],"award-info":[{"award-number":["DSB.AD008.795"]}]},{"name":"Duchenne Parent Project ONLUS (Italy)","award":["SG-2019-12368961"],"award-info":[{"award-number":["SG-2019-12368961"]}]},{"name":"Duchenne Parent Project ONLUS (Italy)","award":["1731651"],"award-info":[{"award-number":["1731651"]}]},{"name":"Duchenne Parent Project ONLUS (Italy)","award":["DSB.AD008.795"],"award-info":[{"award-number":["DSB.AD008.795"]}]},{"name":"National Research Council","award":["SG-2019-12368961"],"award-info":[{"award-number":["SG-2019-12368961"]}]},{"name":"National Research Council","award":["1731651"],"award-info":[{"award-number":["1731651"]}]},{"name":"National Research Council","award":["DSB.AD008.795"],"award-info":[{"award-number":["DSB.AD008.795"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Targeting fibrosis in Duchenne muscular dystrophy (DMD)-associated cardiomyopathy is a critical outstanding clinical issue, as cardiac failure remains a leading cause of death despite advances in supportive care. This study evaluates the therapeutic efficacy of CSPG4-targeted chimeric antigen receptor (CAR) T cells in reducing cardiac fibrosis and improving heart function in a preclinical model of the disease. DMD is a progressive genetic disorder characterized by degeneration of skeletal and cardiac muscle. Cardiomyopathy, driven by fibrosis and chronic inflammation, is a leading contributor to mortality in affected patients. Proteoglycans such as CSPG4, critical regulators of extracellular matrix dynamics, are markedly overexpressed in dystrophic hearts and promote pathological remodeling. Current treatments do not adequately target the fibrotic and inflammatory processes underlying cardiac dysfunction. CSPG4-specific CAR-T cells were engineered and administered to dystrophic mice. Therapeutic efficacy was assessed through histological, molecular, and echocardiographic analyses evaluating cardiac fibrosis, inflammation, innervation, and overall function. Treatment with CSPG4 CAR-T cells preserved myocardial integrity, improved cardiac performance, and reduced both fibrosis and inflammatory markers. The therapy also restored cardiac innervation, indicating a reversal of neural remodeling commonly seen in muscular dystrophy-related cardiomyopathy. CSPG4-targeted CAR-T therapy offers a novel, cell-based strategy to mitigate cardiac remodeling in dystrophic hearts. By addressing core fibrotic and inflammatory drivers of disease, this approach represents a significant advancement in the development of precision immune therapies for muscular dystrophies and cardiovascular conditions.<\/jats:p>","DOI":"10.3390\/ijms26146590","type":"journal-article","created":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T12:46:33Z","timestamp":1752237993000},"page":"6590","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["CSPG4.CAR-T Cells Modulate Extracellular Matrix Remodeling in DMD Cardiomyopathy"],"prefix":"10.3390","volume":"26","author":[{"given":"Maria Grazia","family":"Ceraolo","sequence":"first","affiliation":[{"name":"Neurology Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, 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20054 Segrate, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salma","family":"Bousselmi","sequence":"additional","affiliation":[{"name":"Neurology Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"},{"name":"Ph.D. Program in Cellular and Molecular Biology, Department of Biology, University of Rome \u201cTor Vergata\u201d, Via della Ricerca Scientifica, 1, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4623-6839","authenticated-orcid":false,"given":"Andrea","family":"Soluri","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Cell Biology, National Research Council of Italy (IBBC-CNR), Via Ercole Ramarini, 32, 00015 Monterotondo, 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