{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T11:46:21Z","timestamp":1782301581530,"version":"3.54.5"},"reference-count":53,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T00:00:00Z","timestamp":1781913600000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100031478","name":"NextGenerationEU","doi-asserted-by":"publisher","award":["PNC\u2010E3\u20102022\u201023683269"],"award-info":[{"award-number":["PNC\u2010E3\u20102022\u201023683269"]}],"id":[{"id":"10.13039\/100031478","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100031478","name":"NextGenerationEU","doi-asserted-by":"publisher","award":["CUP code: F83C22002880001"],"award-info":[{"award-number":["CUP code: F83C22002880001"]}],"id":[{"id":"10.13039\/100031478","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JOR Spine"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Intervertebral disc degeneration (IDD) is frequently associated with chronic low back pain (LBP), which contributes significantly to disability, psychological distress, and reduced work capacity. Mesenchymal stromal cell (MSC)\u2010based treatments may offer a promising, less invasive alternative to conventional treatments for IDD. The MSC secretome has shown regenerative potential through paracrine and anti\u2010inflammatory mechanisms. In this study, we investigated the effects of the secretome isolated from interleukin\u20101\u03b2 (IL\u20101\u03b2)\u2010preconditioned bone marrow\u2010derived MSCs (BM\u2010MSCs) on human nucleus pulposus cells (hNPCs) adopting a 3D in\u00a0vitro culture model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The secretome (BM\u2010MSCsec) was collected from BM\u2010MSCs preconditioned with 10\u2009ng\/mL IL\u20101\u03b2. hNPCs were isolated, expanded, encapsulated in alginate beads, and stimulated with IL\u20101\u03b2 to mimic a pro\u2010inflammatory environment. These cells were then treated with either standard culture media (control group), IL\u20101\u03b2 alone, BM\u2010MSCsec, or IL\u20101\u03b2\u2009+\u2009BM\u2010MSCsec. We evaluated cell proliferation and viability via flow cytometry, nitrite and reactive oxygen species (ROS) levels using the H2DCFDA assay, glycosaminoglycan (GAG) content with the 1,9\u2010dimethylmethylene blue assay, gene expression of extracellular matrix (ECM) components and inflammatory markers via qPCR, and cell senescence through Western blot and \u03b2\u2010galactosidase staining.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      IL\u20101\u03b2 stimulation increased hNPC proliferation, nitrite release, ROS production, catabolic and inflammatory gene expression, and cell senescence. Treatment with BM\u2010MSCsec attenuated these effects, restoring proliferation to baseline levels, significantly reducing ROS and nitrite accumulation. BM\u2010MSCsec also upregulated anabolic genes (\n                      <jats:italic>ACAN<\/jats:italic>\n                      ,\n                      <jats:italic>COL2A1<\/jats:italic>\n                      ,\n                      <jats:italic>SOX9<\/jats:italic>\n                      ,\n                      <jats:italic>TIMP\u20101\/3<\/jats:italic>\n                      ), enhanced GAG production, and downregulated\n                      <jats:italic>IL\u20101\u03b2<\/jats:italic>\n                      ,\n                      <jats:italic>IL\u20106<\/jats:italic>\n                      ,\n                      <jats:italic>IL\u20108<\/jats:italic>\n                      ,\n                      <jats:italic>NOS2<\/jats:italic>\n                      ,\n                      <jats:italic>MMP\u20101<\/jats:italic>\n                      , and\n                      <jats:italic>MMP\u201013<\/jats:italic>\n                      expression. Furthermore, senescence was markedly reduced in BM\u2010MSCsec\u2013treated hNPCs, with decreased \u03b2\u2010galactosidase activity and lower p16 and p21 expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings support the potential of BM\u2010MSCsec as a cell\u2010free therapeutic strategy for IDD. The IL\u20101\u03b2\u2010preconditioned secretome reduced hNPC death and senescence, mitigated inflammation and oxidative stress, and promoted ECM preservation, highlighting its potential to counteract key processes driving IDD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jsp2.70199","type":"journal-article","created":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T09:16:21Z","timestamp":1781946981000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pre\u2010Conditioned Bone Marrow Mesenchymal Stromal Cell\u2010Derived Secretome Exerts an Anti\u2010Inflammatory Effect on Degenerative Nucleus Pulposus Cells In\u00a0Vitro"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2233-8171","authenticated-orcid":false,"given":"Veronica","family":"Tilotta","sequence":"first","affiliation":[{"name":"Laboratory for Regenerative Orthopaedics, Operative Research Unit of Orthopaedic and Trauma Surgery Fondazione Policlinico Universitario Campus Bio\u2010Medico  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Vadal\u00e0","sequence":"additional","affiliation":[{"name":"Laboratory for Regenerative Orthopaedics, Operative Research Unit of Orthopaedic and Trauma Surgery Fondazione Policlinico Universitario Campus Bio\u2010Medico  Rome Italy"},{"name":"Research Unit of Orthopaedic and Trauma Surgery, Departmental Faculty of Medicine and Surgery Universit\u00e0 Campus Bio\u2010Medico di Roma  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Ambrosio","sequence":"additional","affiliation":[{"name":"Laboratory for Regenerative Orthopaedics, Operative Research Unit of Orthopaedic and Trauma Surgery Fondazione Policlinico Universitario Campus Bio\u2010Medico  Rome Italy"},{"name":"Research Unit of Orthopaedic and Trauma Surgery, Departmental Faculty of Medicine and Surgery Universit\u00e0 Campus Bio\u2010Medico di Roma  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppina","family":"Di Giacomo","sequence":"additional","affiliation":[{"name":"Laboratory for Regenerative Orthopaedics, Operative Research Unit of Orthopaedic and Trauma Surgery Fondazione Policlinico Universitario Campus Bio\u2010Medico  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Cicione","sequence":"additional","affiliation":[{"name":"Laboratory for Regenerative Orthopaedics, Operative Research Unit of Orthopaedic and Trauma Surgery Fondazione Policlinico Universitario Campus Bio\u2010Medico  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8566-8952","authenticated-orcid":false,"given":"Fabrizio","family":"Russo","sequence":"additional","affiliation":[{"name":"Laboratory for Regenerative Orthopaedics, Operative Research Unit of Orthopaedic and Trauma Surgery Fondazione Policlinico Universitario Campus Bio\u2010Medico  Rome Italy"},{"name":"Research Unit of Orthopaedic and Trauma Surgery, Departmental Faculty of Medicine and Surgery Universit\u00e0 Campus Bio\u2010Medico di Roma  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rocco","family":"Papalia","sequence":"additional","affiliation":[{"name":"Laboratory for Regenerative Orthopaedics, Operative Research Unit of Orthopaedic and Trauma Surgery Fondazione Policlinico Universitario Campus Bio\u2010Medico  Rome Italy"},{"name":"Research Unit of Orthopaedic and Trauma Surgery, Departmental Faculty of Medicine and Surgery Universit\u00e0 Campus Bio\u2010Medico di Roma  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Denaro","sequence":"additional","affiliation":[{"name":"Laboratory for Regenerative Orthopaedics, Operative Research Unit of Orthopaedic and Trauma Surgery Fondazione Policlinico Universitario Campus Bio\u2010Medico  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,20]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/2192568218770769"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/app15126660"},{"key":"e_1_2_10_4_1","article-title":"Intervertebral Disc Degeneration and How It Leads to Low Back Pain","volume":"6","author":"Diwan A. 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