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An insufficiently inflammatory environment can fail to activate MSCs, and certain signals can impair their function. Obesity is on the rise worldwide, making it an additional factor to be considered prior to MSC therapy, as the microenvironment presents its own challenges. Elevated levels of serum free fatty acids, specifically palmitate, have the potential to affect MSC therapy. Palmitate-exposure has been shown to impair MSC immunomodulation of T cells in vitro. However, this is yet to be studied in the context of macrophages.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>MSCs from three independent donors were exposed to 0.4mM of palmitate for 6\u201324\u00a0h. Gene expression, protein production and functional capacity were then assessed in response to palmitate. A ceramide synthesis inhibitor (Fumonisin B1) and a CC-chemokine ligand 2 (CCL2)-neutralising antibody were further used to assess the impact of these components on palmitate-associated immunomodulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We demonstrated that palmitate-exposed MSCs have enhanced suppression of human monocyte-derived macrophage (MDM) production of tumour necrosis factor \u03b1 (TNF\u03b1), in a CCL2-dependent manner. We further elucidated parts of the pathway, such as ceramide synthesis, through which palmitate promotes this enhanced immunomodulation of macrophages.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Palmitate-exposed MSCs show enhanced immunomodulation of human MDMs, through the ceramide\/CCL2 axis in vitro.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13287-025-04536-7","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T18:28:35Z","timestamp":1754504915000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Palmitate enhances MSC immunomodulation of human macrophages via the ceramide\/CCL2 axis in vitro"],"prefix":"10.1186","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5343-7984","authenticated-orcid":false,"given":"Courteney","family":"Tunstead","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4265-6660","authenticated-orcid":false,"given":"Laura M.","family":"Bitterlich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3959-6158","authenticated-orcid":false,"given":"James A.","family":"Ankrum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5875-230X","authenticated-orcid":false,"given":"Andrew E.","family":"Hogan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7932-4256","authenticated-orcid":false,"given":"Karen","family":"English","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,6]]},"reference":[{"key":"4536_CR1","doi-asserted-by":"publisher","unstructured":"Galleu A, Riffo-Vasquez Y, Trento C, Lomas C, Dolcetti L, Cheung TS, et al. 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All patients gave written informed consent prior to partaking in the study. RoosterBio (company where the human BM-MSCs were purchased) has confirmed that there was initial ethical approval for collection of human cells, and that the donors had signed informed consent. RoosterBio state \u201cRoosterBio sources commercially available in vitro research only human bone marrow aspirate from qualified donors. All human bone marrow aspirate collections are from healthy adult consented donors. Collection protocols and the donor-informed consent document are approved by an Institutional Review Board (IRB)\u201d.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate statement"}},{"value":"The authors declare that they have not used AI-generated work in this manuscript.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Use of AI"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"435"}}