{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:55:00Z","timestamp":1790916900866,"version":"4.1.0"},"reference-count":38,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Multiple myeloma (MM) depends on a permissive bone marrow microenvironment that supports malignant plasma cell survival and disease progression. Bone marrow mesenchymal stromal cells (BM-MSCs) are key components of this niche, but the mechanisms by which they are recruited by MM cells remain unclear. Here, we show that the MM-derived secretome (MM-Sec) promotes BM-MSC wound closure and transwell migration-associated responses in vitro. A small extracellular vesicle (sEV)-enriched pellet was isolated from MM.1S-Sec by differential ultracentrifugation and characterized, and the relative contributions of the sEV-enriched fraction and sEV-depleted secretome (post-100,000\u00d7 g) to BM-MSC migration were assessed. The results show that the sEV-depleted secretome is more effective than the sEV-enriched fraction in promoting BM-MSC recruitment. Chemokine profiling of MM.1S-Sec identified CCL3 (MIP-1\u03b1) and CCL5 (RANTES) as abundant secreted factors and exploratory candidate contributors. Recombinant CCL3 and CCL5 increased the BM-MSC transwell migration response at high concentrations. Priming with MM.1S-Sec was associated with increased transwell migration-associated responses in the presence of CCL3 and CCL5. Together, these exploratory findings suggest that both vesicle-associated and soluble non-vesicular components may contribute to BM-MSC migration, while CCL3 and CCL5 may participate as candidate contributors within a broader network of soluble mediators. These findings identify secretome-mediated modulation of stromal migration as a relevant component of MM\u2013microenvironment crosstalk that warrants further mechanistic investigation.<\/jats:p>","DOI":"10.3390\/ijms27198763","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:01:19Z","timestamp":1790773279000},"page":"8763","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multiple Myeloma Cell-Derived Secretome Modulates Bone Marrow Mesenchymal Stromal Cell Migration In Vitro"],"prefix":"10.3390","volume":"27","author":[{"given":"Maria Jo\u00e3o","family":"Fernandes","sequence":"first","affiliation":[{"name":"i3S, Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal"},{"name":"ICBAS, Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"given":"Andrea","family":"Giestinhas","sequence":"additional","affiliation":[{"name":"i3S, Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal"},{"name":"INEB, Instituto de Engenharia Biom\u00e9dica, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"given":"Sara Reis","family":"Moura","sequence":"additional","affiliation":[{"name":"i3S, Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Maria Helena","family":"Vasconcelos","sequence":"additional","affiliation":[{"name":"i3S, Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal"},{"name":"Laborat\u00f3rio de Microbiologia, Faculdade de Farm\u00e1cia (FFUP), Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana Gomes","family":"Santos","sequence":"additional","affiliation":[{"name":"i3S, Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal"},{"name":"INEB, Instituto de Engenharia Biom\u00e9dica, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Jos\u00e9","family":"Oliveira","sequence":"additional","affiliation":[{"name":"i3S, Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal"},{"name":"INEB, Instituto de Engenharia 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Portugal"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41408-017-0037-4","article-title":"Pathogenesis of bone disease in multiple myeloma: From bench to bedside","volume":"8","author":"Terpos","year":"2018","journal-title":"Blood Cancer J."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Eisfeld, C., Kaj\u00fcter, H., M\u00f6ller, L., Wellmann, I., Shumilov, E., and Stang, A. 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