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MSC derived from human adipose tissue were left untreated in resting state (rMSC), conditioned by PBMC (cMSC), or activated by the pro-inflammatory molecule interferon (IFN)-\u03b3 (\u03b3MSC), then compared for their gene expression profiles, phenotypes and functional capacities.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>RNA sequencing identified 244 differentially expressed genes in cMSC compared to rMSC, highlighting key immune mediators such as <jats:italic>CCL2<\/jats:italic>, <jats:italic>CCL11<\/jats:italic>,<jats:italic> DPP4<\/jats:italic>,<jats:italic> ICAM1<\/jats:italic>,<jats:italic> IL6<\/jats:italic>,<jats:italic> PDCD1LG2<\/jats:italic>,<jats:italic> TNFRSF11B<\/jats:italic>,<jats:italic> TNIP1<\/jats:italic>,<jats:italic> TNIP3<\/jats:italic> and <jats:italic>ZC3H12A<\/jats:italic> and pinpointing genes involved in matrix remodeling, paracrine and autocrine communications. Comparatively, 2089 genes were differentially expressed between rMSC and \u03b3MSC, highlighting host defense, anti-viral response, NF\u03baB signaling pathways modulated by IFN-\u03b3. Flow and mass cytometry analyses revealed upregulation of the surface markers CD26, CD54, and CD273 and intracellular molecules IDO1 and PTGS2 in cMSC. In contrast, IFN-\u03b3 activation predominantly increased HLA-related markers while also enhancing the homogeneity of the populations. Together, these results underlined the treatment dependence of transcriptomic and phenotypic signatures. Secretome profiling identified 6 categories of modulated proteins, out of which 22 molecules potentially involved in PBMC conditioning and 40 implicated in cMSC-mediated immunomodulation. Functionally, cMSC induced modulation in PBMC subsets, raising the proportions of lymphocyte populations (CD4 Treg, CD8, B memory), underlining the multimodal effect of conditioning. Also, both a direct cell-cell contact and cMSC supernatants significantly suppressed activated T-cell proliferation in vitro. To confirm immunomodulation efficacy in vivo, cMSC were administrated to our humanized mouse model of Myasthenia Gravis and the treatment significantly halved disease severity from 2 weeks post-injection.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>This integrative study establishes distinct conditioning signatures, suggests molecular mechanisms, and underscores the therapeutic potential of cMSC, offering a robust framework for advancing cell-based therapies in autoimmune diseases.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s13287-025-04534-9","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T10:26:17Z","timestamp":1754648777000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Mesenchymal stromal cells conditioned by peripheral blood mononuclear cells exert enhanced immunomodulation capacities and alleviate a model of Myasthenia Gravis"],"prefix":"10.1186","volume":"16","author":[{"given":"Alexandra C.","family":"Bayer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Pinz\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"You","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinthia","family":"Bergman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Dragin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lien","family":"Corneau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9rique","family":"Truffault","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dani\u00e8le","family":"No\u00ebl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Martinaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rozen","family":"Le Panse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Berrih-Aknin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0050-0219","authenticated-orcid":false,"given":"Jean-Thomas","family":"Vilquin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,8]]},"reference":[{"issue":"10","key":"4534_CR1","doi-asserted-by":"publisher","first-page":"1152","DOI":"10.1016\/j.jcyt.2017.07.001","volume":"19","author":"E Andreeva","year":"2017","unstructured":"Andreeva E, Bobyleva P, Gornostaeva A, Buravkova L. 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Cell Immunol. 2008;251(2):131\u20136.","journal-title":"Cell Immunol"}],"container-title":["Stem Cell Research &amp; Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13287-025-04534-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13287-025-04534-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13287-025-04534-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T19:43:27Z","timestamp":1757360607000},"score":1,"resource":{"primary":{"URL":"https:\/\/stemcellres.biomedcentral.com\/articles\/10.1186\/s13287-025-04534-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,8]]},"references-count":109,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["4534"],"URL":"https:\/\/doi.org\/10.1186\/s13287-025-04534-9","relation":{},"ISSN":["1757-6512"],"issn-type":[{"value":"1757-6512","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,8]]},"assertion":[{"value":"21 March 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 July 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 August 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Human adipose-derived MSC were obtained in the context of two successive clinical trials and used as res nullius. (1) The title of the aproved projects were ADIPOA (A Phase I, Prospective, bi-centric, single-arm, open-label, dose-escalating clinical trial to evaluate the safety of a single injection of autologous adipose derived mesenchymal stromal cells in the treatment of severe osteoarthritis of the nee joint) and ADIPOA-2 (A study evaluating the efficacy of a single injection of autologous adipose derived mesenchymal stromal cells in patients with knee osteoarthritis). (2) They were authorized by the Personal Protection Committee of Montpellier, France, UF 606-120203. (3) The registered numbers are NCT01585857 and NCT02838069. (4) The projects were approved on 12\/2011 and 09\/2016. According to the French laws and regulations, the patients provided written informed consent for use of their cells and were anonymized. AChR+MG thymic fragments were provided by medical collaborators with the authorization of a French Ethical Committee. (1) The title of the approved project was MYA-PATH (Constitution of a collection of biological resources for the study of pathologies that could lead to autoimmune myasthenia). (2) It was authorized by the Personal Protection Committee of Tours, Central West Region 1, France, IRB n\u00b0 IORG0008143 OMB: 0990\u2009\u2212\u20090279, (3) under agreement number 2019-A01482-55, (4) in date of 11\/20\/2019. The patients were undergoing thymectomy and gave written informed consent for the use of res nullius samples obtained during surgeries and anonymized according to the French laws and regulations. Whole blood bags were procured by the French Blood Establishment (EFS Ile de France) to prepare PBMC according to the convention CCPSL UNT\u2013 N\u00b0 18\/EFS\/033 authorized on 16\/08\/2018 between our Institutions. According to French laws and regulations (article R.1222-40\/2 of the Public Health Code), the EFS collect and distribute blood elements prepared from donors, whose gift is free and anonymous, and who gave written informed consent for their use. No further IRB was required. Animal experimentations have been designed to respect the 3R principles according to the Directive 2010\/63\/EU of the European Union and received the APAFIS authorizations number 02622.2 (Evaluation of cellular and pharmacological therapeutic strategies in the experimental mouse model of Myasthenia gravis, 20\/11\/2015) and number 30172 (Set up of cellular therapy strategies in two experimental mouse models of Myasthenia gravis, 21\/05\/2021), from the French Ministry of Higher Education and Research under agreement of the local Ethical Committee (CEEA 005, Charles Darwin). Experimentations were performed under supervision of personals authorized by French Authorities in the animal facility of the Sorbonne University (EU 0144, Agreement C-75-13-20).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing financial or personal interests that could have influenced the work reported in this article.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"437"}}