{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:29:08Z","timestamp":1787243348476,"version":"build-2736575974"},"reference-count":68,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondazione Poliambulanza, Brescia and MIUR","award":["5x1000"],"award-info":[{"award-number":["5x1000"]}]},{"name":"Contributi per il funzionamento degli Enti privati che svolgono attivit\u00e0 di ricerca"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Mesenchymal stromal cells from the amniotic membrane (hAMSCs) counteract fibrosis progression, primarily via anti-inflammatory effects like promoting macrophage polarization toward an anti-inflammatory, pro-regenerative phenotype. Methods: We investigated hAMSCs\u2019 ability to prevent and halt lung fibrosis in a bleomycin-induced fibrosis murine model. We focused on their impact on recruitment and polarization of different macrophage populations, including SPARC- and CD169-expressing macrophages, implicated in resolving pulmonary inflammation and fibrosis. Results: hAMSCs, administered early (concomitant with bleomycin, during acute inflammation), or late (at day 7 post-bleomycin, during established fibrosis), showed anti-fibrotic activity, preserving alveolar area, reducing the extent of lung fibrosis, and decreasing \u03b1-SMA levels. These preventive and late anti-fibrotic effects of hAMSCs are associated with a context-dependent presence of distinct macrophage signatures. Early treatment reduced macrophage recruitment and increased levels of Arg1+\/iNOS\u2212 macrophages, curbing injury-induced inflammation. Late treatment uniquely increased the lung levels of CD169+ macrophages, suggesting their contribution to hAMSCs\u2019 anti-fibrotic effect. We hypothesized a potential involvement of lung CD169+ macrophages in promoting recruitment of regulatory T cells (Tregs) to the lungs. Although these macrophages can establish a CCL22-CCR4 axis with Tregs, and treatment effectively boosted Treg lung levels, the Treg increase is not directly attributable to higher CD169+ macrophage numbers, implying other potentially IL-10-driven mechanisms. Conclusions: hAMSC treatment effectively prevents and blocks lung fibrosis. These effects are associated with distinct lung macrophage marker profiles, suggesting a potential involvement of different macrophage populations in a time-dependent manner; thus highlighting administration timing\u2019s role in optimizing therapeutic synergy.<\/jats:p>","DOI":"10.3390\/pharmaceutics18081039","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:05:19Z","timestamp":1787241919000},"page":"1039","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Amniotic Mesenchymal Stromal Cell Administration Prevents and Stops Lung Fibrosis and Is Associated with Distinct Macrophage Signatures"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8617-1139","authenticated-orcid":false,"given":"Anna","family":"Cargnoni","sequence":"first","affiliation":[{"name":"Centro di Ricerca E. Menni, Fondazione Poliambulanza Istituto Ospedaliero, 25124 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serafina","family":"Farigu","sequence":"additional","affiliation":[{"name":"Centro di Ricerca E. Menni, Fondazione Poliambulanza Istituto Ospedaliero, 25124 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0721-3300","authenticated-orcid":false,"given":"Pietro","family":"Romele","sequence":"additional","affiliation":[{"name":"Centro di Ricerca E. Menni, Fondazione Poliambulanza Istituto Ospedaliero, 25124 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1229-9671","authenticated-orcid":false,"given":"Andrea","family":"Papait","sequence":"additional","affiliation":[{"name":"Department of Life Science and Public Health, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Fondazione Policlinico Universitario \u201cAgostino Gemelli\u201d, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Magatti","sequence":"additional","affiliation":[{"name":"Centro di Ricerca E. Menni, Fondazione Poliambulanza Istituto Ospedaliero, 25124 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6208-3583","authenticated-orcid":false,"given":"Antonietta","family":"Silini","sequence":"additional","affiliation":[{"name":"Centro di Ricerca E. Menni, Fondazione Poliambulanza Istituto Ospedaliero, 25124 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5211-6430","authenticated-orcid":false,"given":"Ornella","family":"Parolini","sequence":"additional","affiliation":[{"name":"Department of Life Science and Public Health, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"405","DOI":"10.3727\/096368909788809857","article-title":"Transplantation of Allogeneic and Xenogeneic Placenta-Derived Cells Reduces Bleomycin-Induced Lung Fibrosis","volume":"18","author":"Cargnoni","year":"2009","journal-title":"Cell Transplant."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1002\/sctm.20-0068","article-title":"Amniotic MSCs Reduce Pulmonary Fibrosis by Hampering Lung B-Cell Recruitment, Retention, and Maturation","volume":"9","author":"Cargnoni","year":"2020","journal-title":"Stem Cells Transl. 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