{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T11:28:51Z","timestamp":1782991731877,"version":"3.54.5"},"reference-count":84,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Agency for the Promotion of Science and Technology","award":["PICT 2021-I-A-0807"],"award-info":[{"award-number":["PICT 2021-I-A-0807"]}]},{"name":"National Agency for the Promotion of Science and Technology","award":["PICT 2015-0152"],"award-info":[{"award-number":["PICT 2015-0152"]}]},{"DOI":"10.13039\/501100002923","name":"National Scientific and Technical Research Council","doi-asserted-by":"crossref","award":["PIP 2022-0763"],"award-info":[{"award-number":["PIP 2022-0763"]}],"id":[{"id":"10.13039\/501100002923","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100008056","name":"Florencio Fiorini Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008056","id-type":"DOI","asserted-by":"crossref"}]},{"name":"CAHTalizar 2023"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chronic hemophilic synovitis (CHS), driven by hemosiderin-laden macrophages from recurrent hemarthrosis, is a major cause of joint damage in hemophilia. Platelet-rich plasma (PRP) is a promising regenerative therapy for joint diseases. This study investigated PRP\u2019s ability to modulate macrophage polarization from a pro-inflammatory (M1) to a pro-resolving, tissue-repairing (M2) phenotype in CHS. We analyzed synovial fluid (SF) from CHS patients (N = 22), both pre- and post-PRP treatment. Ex vivo analysis revealed a predominant M1 profile with an increased proportion of CD11+CD14+CD64hi compared with CD206+ or CD163+ M2 macrophages in CHS SF. In vitro experiments showed that CHS SF skewed monocyte-derived macrophages toward an M1 inflammatory program, evaluated by flow cytometry, qPCR, and ELISA. However, adding PRP significantly modulated the pro-inflammatory macrophage program, promoting an M2 tissue repair profile. Furthermore, a random forest machine learning algorithm, applied to public scRNAseq data, confirmed PRP\u2019s macrophage reprogramming effect. Functional assays also showed increased TGF-\u03b2 secretion and macrophage fusion when challenged with neutrophil extracellular traps (NETs). A small patient follow-up cohort treated with intra-articular PRP showed similar results, including normalization of cellular content and reduced CD64\/CD206 expression. These findings indicate that PRP treatment effectively shifts SF-associated M1 macrophages to an M2-like phenotype, highlighting its potential as a therapeutic strategy for CHS.<\/jats:p>","DOI":"10.3390\/ijms262110616","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T13:15:14Z","timestamp":1762175714000},"page":"10616","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Platelet Releasate Reprograms Synovial Macrophages In Vitro: A New Approach in the Treatment of Hemophilic Synovitis"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2748-7587","authenticated-orcid":false,"given":"Paula","family":"Oneto","sequence":"first","affiliation":[{"name":"Institute of Experimental Medicine (IMEX), CONICET, National Academy of Medicine, Buenos Aires C1425AUM, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9185-2430","authenticated-orcid":false,"given":"Mar\u00eda Eulalia","family":"Landro","sequence":"additional","affiliation":[{"name":"Department of Traumatology, Juan A. Fern\u00e1ndez Hospital, Buenos Aires C1425AGP, Argentina"},{"name":"Haemophilia Foundation, Buenos Aires C1425BWE, Argentina"},{"name":"School of Medicine, Argentine Catholic University, Buenos Aires C1107AAZ, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9080-2108","authenticated-orcid":false,"given":"Martin Manuel","family":"Ledesma","sequence":"additional","affiliation":[{"name":"Institute of Experimental Medicine (IMEX), CONICET, National Academy of Medicine, Buenos Aires C1425AUM, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Etulain","sequence":"additional","affiliation":[{"name":"Institute of Experimental Medicine (IMEX), CONICET, National Academy of Medicine, Buenos Aires C1425AUM, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2612-2105","authenticated-orcid":false,"given":"Carla","family":"Daffunchio","sequence":"additional","affiliation":[{"name":"Department of Traumatology, Juan A. Fern\u00e1ndez Hospital, Buenos Aires C1425AGP, Argentina"},{"name":"Haemophilia Foundation, Buenos Aires C1425BWE, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo","family":"Cambiaggi","sequence":"additional","affiliation":[{"name":"Department of Traumatology, Juan A. Fern\u00e1ndez Hospital, Buenos Aires C1425AGP, Argentina"},{"name":"Haemophilia Foundation, Buenos Aires C1425BWE, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirta","family":"Schattner","sequence":"additional","affiliation":[{"name":"Institute of Experimental Medicine (IMEX), CONICET, National Academy of Medicine, Buenos Aires C1425AUM, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea Emilse","family":"Errasti","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, School of Medicine, University of Buenos Aires, Buenos Aires C1053ABH, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Horacio","family":"Caviglia","sequence":"additional","affiliation":[{"name":"Haemophilia Foundation, Buenos Aires C1425BWE, Argentina"},{"name":"School of Medicine, Argentine Catholic University, Buenos Aires C1107AAZ, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4428-8213","authenticated-orcid":false,"given":"Eugenio Antonio","family":"Carrera Silva","sequence":"additional","affiliation":[{"name":"Institute of Experimental Medicine (IMEX), CONICET, National Academy of Medicine, Buenos Aires C1425AUM, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Melchiorre, D., Manetti, M., and Matucci-Cerinic, M. 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