{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T19:41:10Z","timestamp":1775850070502,"version":"3.50.1"},"reference-count":0,"publisher":"Forum Multimedia Publishing LLC","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["eCM"],"abstract":"<jats:p>Mesenchymal stem\/stromal cells (MSCs) have been increasingly used in clinical trials for low-back pain (LBP) and intervertebral disc (IVD) degeneration with promising results. Their action mechanisms are not fully understood, but they reduce IVD pro-inflammatory markers in a pro-inflammatory\/degenerative IVD microenvironment. In this study the therapeutic potential of the MSC secretome, as an alternative cell-free approach for treating degenerated IVDs, was examined. Human bone marrow-derived MSC secretome (MSCsec) was collected after 48 h of preconditioning in IL-1\u03b2 (10 ng\/mL) and low oxygen (6 % O2), mimicking the degenerative IVD. IL-1\u03b2-pre-conditioning of MSCs increased secretion of pro-inflammatory markers hIL-6, hIL-8, hMCP-1, etc. The therapeutic effect of MSCsec was tested in a pro-inflammatory\/degenerative IVD ex vivo model. MSCsec down-regulated IVD gene expression of pro-inflammatory cytokines (bIL-6, bIL-8) and matrix degrading enzyme bMMP1, while bMMP3 and bTIMP2 were up-regulated, at 48 h. After 14 d, MSCsec-treated IVDs revealed increased aggrecan deposition, although no differences in other ECM components were observed. Protein analysis of the MSCsec-treated IVD supernatant revealed a significant increase of CXCL1, MCP-1, MIP-3\u03b1, IL-6, IL-8 and GRO \u03b1\/\u03b2\/\u03b3 (related to TNF, NOD-like receptor and neutrophil chemotaxis signalling), and a decrease of IFN-\u03b3, IL-10, IL-4, IL-5 and TNF-\u03b1 (associated with T-cell receptor signalling). MSCsec-treated IVD supernatants did not promote angiogenesis and neurogenesis in vitro. Overall, MSCsec can be a safe therapeutic approach, presenting a strong immunomodulatory role in degenerated IVD while potentiating aggrecan deposition, which can open new perspectives on the use of MSCsec as a cell-based\/ cell-free therapeutic approach to LBP.<\/jats:p>","DOI":"10.22203\/ecm.v041a28","type":"journal-article","created":{"date-parts":[[2021,4,20]],"date-time":"2021-04-20T14:35:55Z","timestamp":1618929355000},"page":"431-543","source":"Crossref","is-referenced-by-count":29,"title":["IL-1\u03b2-pre-conditioned mesenchymal stem\/stromal cells\u2019 secretome modulates the inflammatory response and aggrecan deposition in intervertebral disc"],"prefix":"10.22203","volume":"41","author":[{"name":"I3S \u2013 Rua Alfredo Allen 208, 4200-135 Porto, Portugal","sequence":"first","affiliation":[]},{"given":"JR","family":"Ferreira","sequence":"first","affiliation":[]},{"given":"GQ","family":"Teixeira","sequence":"additional","affiliation":[]},{"given":"e","family":"Neto","sequence":"additional","affiliation":[]},{"given":"c","family":"Ribeiro-Machado","sequence":"additional","affiliation":[]},{"given":"AM","family":"Silva","sequence":"additional","affiliation":[]},{"given":"J","family":"Caldeira","sequence":"additional","affiliation":[]},{"given":"C","family":"Leite Pereira","sequence":"additional","affiliation":[]},{"given":"S","family":"Bidarra","sequence":"additional","affiliation":[]},{"given":"AF","family":"Maia","sequence":"additional","affiliation":[]},{"given":"M","family":"Lamghari","sequence":"additional","affiliation":[]},{"given":"MA","family":"Barbosa","sequence":"additional","affiliation":[]},{"given":"RM","family":"Gon\u00e7alves","sequence":"additional","affiliation":[]}],"member":"39461","published-online":{"date-parts":[[2021,4,20]]},"container-title":["European Cells and Materials"],"original-title":[],"link":[{"URL":"https:\/\/www.ecmjournal.org\/papers\/vol041\/pdf\/v041a28.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,20]],"date-time":"2021-04-20T14:35:56Z","timestamp":1618929356000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ecmjournal.org\/papers\/vol041\/pdf\/v041a28.pdf"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,20]]},"references-count":0,"URL":"https:\/\/doi.org\/10.22203\/ecm.v041a28","relation":{},"subject":[],"published":{"date-parts":[[2021,4,20]]}}}