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Here, we compare two MSC priming strategies: coculture with regulatory T cell (Treg) or exposure to the proresolving mediator Resolvin E1 (RvE1) to enhance ectopic osteogenesis in mice. Both approaches enhance MSC\u2010mediated bone formation through distinct local and systemic immunomodulatory mechanisms. Treg priming promotes a regulated anti\u2010inflammatory environment characterized by reduced IL\u20106 protein levels (3.6\u2010fold), sustained IL\u201013 elevation up to 10 weeks (1.5\u2010fold compared with RvE1), early suppression of cytotoxic CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells and IFN\u2010\u03b3 production by CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells in lymph nodes, a &gt;25% reduction in fibrous capsule formation, and enhanced B cell activity, collectively supporting ossification. In contrast, RvE1 priming promotes early TNF\u2010\u03b1 and late granulocyte\u2010macrophage colony\u2010stimulating factor (GM\u2010CSF) production (1.2\u2010fold compared with Treg) within the scaffold, facilitating osteoblast maturation. Transcriptomic profiling revealed distinct osteogenic signatures, with amphiregulin uniquely upregulated in the Treg group (&gt;7\u2010fold). Using a Treg depletion model, we further demonstrate that RvE1 retains partial immunomodulatory capacity and supports matrix organization. Together, these findings underscore the versatility of immune modulation in directing MSC fate and highlight the potential of tailoring immunoregulatory strategies to optimize bone regeneration.\n                  <\/jats:p>","DOI":"10.1002\/advs.202518026","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T19:07:46Z","timestamp":1772996866000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Distinct Immunomodulatory Strategies Guide Mesenchymal Stromal\/Stem Cell\u2010Mediated Bone Regeneration"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0385-6157","authenticated-orcid":false,"given":"Salwa","family":"Suliman","sequence":"first","affiliation":[{"name":"Department of Clinical Dentistry Faculty of Medicine Centre For Translational Oral Research (TOR) University of Bergen  Bergen Norway"},{"name":"The ADA Forsyth Institute  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla Alvarez","family":"Rivas","sequence":"additional","affiliation":[{"name":"The ADA Forsyth Institute  Cambridge Massachusetts USA"},{"name":"Oral Biology Department School of Dental Medicine University at Buffalo  Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aashish","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Genome Core Facility Department of Clinical Science University of Bergen  Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora","family":"Marek","sequence":"additional","affiliation":[{"name":"Department of Clinical Dentistry Faculty of Medicine Centre For Translational Oral Research (TOR) University of Bergen  Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamal","family":"Mustafa","sequence":"additional","affiliation":[{"name":"Department of Clinical Dentistry Faculty of Medicine Centre For Translational Oral Research (TOR) University of Bergen  Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alpdogan","family":"Kantarci","sequence":"additional","affiliation":[{"name":"The ADA Forsyth Institute  Cambridge Massachusetts USA"},{"name":"Department of Developmental and Surgical Sciences School of Dentistry University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,5]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11914\u2010022\u201000742\u2010x"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/SCS.0000000000005250"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287\u2010018\u20100951\u20109"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s41232\u2010023\u201000279\u20101"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01954"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00562"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2013.0673"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577\u2010021\u201000519\u2010w"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/cei\/uxac076"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2015.00184"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010020\u201076038\u2010w"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2542"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.10.054"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2022.121604"},{"key":"e_1_2_10_16_1","first-page":"1","article-title":"Priming Approaches to Improve the Efficacy of Mesenchymal Stromal Cell\u2010Based Therapies","volume":"10","author":"Noronha N. 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