{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T03:49:19Z","timestamp":1793245759276,"version":"4.5.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T00:00:00Z","timestamp":1643328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioeng. Biotechnol."],"abstract":"<jats:p>\n                    Mesenchymal stem\/stromal cell (MSC)\u2013based therapies for low back pain and intervertebral disc (IVD) degeneration have been emerging, despite the poor knowledge of their full mechanism of action. As failure of the annulus fibrosus (AF) is often associated with IVD herniation and inflammation, the objective of the present study was to investigate the impact of the MSC secretome on human AF cells exposed to mechanical loading and a pro-inflammatory environment. Human AF cells isolated from IVD biopsies from patients with adolescent idiopathic scoliosis (AIS) or disc degeneration (DD) were exposed to physiological cyclic tensile strain (CTS) for 72\u00a0h in a custom-made device, with or without interleukin (IL)-1\u03b2 medium supplementation. AF cells stimulated with CTS + IL-1\u03b2 were then treated with secretome from IL-1\u03b2\u2013preconditioned MSCs for 48\u00a0h. AF cell metabolic activity, gene expression, protein secretion, matrix metalloproteinase (MMP) activity, and tissue inhibitor of MMPs (TIMP) concentration were evaluated. Expanded AF cells from AIS and DD patients revealed similar metabolic activity and gene expression profiles. CTS stimulation upregulated collagen type I (\n                    <jats:italic>COL1A1<\/jats:italic>\n                    ) expression, while IL-1\u03b2 significantly stimulated\n                    <jats:italic>IL-6<\/jats:italic>\n                    ,\n                    <jats:italic>IL-8<\/jats:italic>\n                    ,\n                    <jats:italic>MMP-1<\/jats:italic>\n                    , and\n                    <jats:italic>MMP-3<\/jats:italic>\n                    gene expression and prostaglandin E\n                    <jats:sub>2<\/jats:sub>\n                    production by AF cells but downregulated\n                    <jats:italic>COL1A1<\/jats:italic>\n                    . The combination of CTS + IL-1\u03b2 had a similar outcome as IL-1\u03b2 alone, accompanied by a significant upregulation of elastin. The MSC secretome did not show any immunomodulatory effect on CTS + IL-1\u03b2\u2013stimulated AF cells but significantly decreased\n                    <jats:italic>MMP-1<\/jats:italic>\n                    , MMP-2,\n                    <jats:italic>MMP-3<\/jats:italic>\n                    , and\n                    <jats:italic>MMP-9<\/jats:italic>\n                    , while increasing the production of TIMP-1. The obtained results demonstrate a stronger impact of the inflammatory milieu on human AF cells than upper physiologic mechanical stress. In addition, a new MSC mechanism of action in degenerated IVD consisting of the modulation of AF MMP activity was also evidenced, contributing to the advancement of knowledge in AF tissue metabolism.\n                  <\/jats:p>","DOI":"10.3389\/fbioe.2021.802789","type":"journal-article","created":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T01:38:46Z","timestamp":1643333926000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Interleukin-1\u03b2 More Than Mechanical Loading Induces a Degenerative Phenotype in Human Annulus Fibrosus Cells, Partially Impaired by Anti-Proteolytic Activity of Mesenchymal Stem Cell Secretome"],"prefix":"10.3389","volume":"9","author":[{"given":"Raquel M.","family":"Gon\u00e7alves","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taryn","family":"Saggese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyao","family":"Yong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joana R.","family":"Ferreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Ignatius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Joachim","family":"Wilke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia","family":"Neidlinger-Wilke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graciosa Q.","family":"Teixeira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"804","DOI":"10.1089\/scd.2012.0179","article-title":"The Presence of Local Mesenchymal Progenitor Cells in Human Degenerated Intervertebral Discs and Possibilities to Influence These In Vitro: a Descriptive Study in Humans","volume":"22","author":"Brisby","year":"2013","journal-title":"Stem Cell Development."},{"key":"B2","doi-asserted-by":"publisher","first-page":"2123","DOI":"10.1038\/onc.2013.154","article-title":"Macrophages Stimulate Gastric and Colorectal Cancer Invasion through EGFR Y1086, C-Src, Erk1\/2 and Akt Phosphorylation and smallGTPase Activity","volume":"33","author":"Cardoso","year":"2014","journal-title":"Oncogene."},{"key":"B3","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1007\/s12015-012-9364-9","article-title":"IL1\u03b2 Induces Mesenchymal Stem Cells Migration and Leucocyte Chemotaxis Through NF-\u039ab","volume":"8","author":"Carrero","year":"2012","journal-title":"Stem Cell Rev Rep."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1826","DOI":"10.1097\/brs.0b013e3181132a9d","article-title":"Elastin Content Correlates with Human Disc Degeneration in the Anulus Fibrosus and Nucleus Pulposus","volume":"32","author":"Cloyd","year":"2007","journal-title":"Spine."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.5966\/sctm.2016-0033","article-title":"Systemic Delivery of Bone Marrow Mesenchymal Stem Cells for In Situ Intervertebral Disc Regeneration","volume":"6","author":"Cunha","year":"2017","journal-title":"Stem Cell Transl. 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