{"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":1782301581523,"version":"3.54.5"},"reference-count":104,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/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\/100010663","name":"H2020 European Research Council","doi-asserted-by":"publisher","award":["ERC\u20102019\u2010CoG\u2010864104; INTEGRATE"],"award-info":[{"award-number":["ERC\u20102019\u2010CoG\u2010864104; INTEGRATE"]}],"id":[{"id":"10.13039\/100010663","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 (IVD) degeneration is the primary cause of low back pain (LBP). Disease progression is characterized by a shift in extracellular matrix homeostasis towards degradation over regeneration, a process that is a key target of emerging therapeutic strategies. Our laboratory has previously identified the dual delivery of FLR\u2010miRNA\u2010149\u20105p mimic and 221\u20103p inhibitor as being beneficial in generating an anti\u2010catabolic regenerative niche. Cell therapies have likewise demonstrated potential, though the most suitable cell source has been debated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>In this study, we explored the stimulation of nucleus pulposus and bone marrow derived stem cells with our therapeutic miRNA pair, with the aim of identifying the most suitable cell population for delivery to the IVD. Culture systems of increasing complexity ranging from monolayer to ex\u00a0vivo organ culture were employed using caprine cells and IVD organs due to their physiological relevance to humans.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We demonstrated the maintenance of our previously reported anti\u2010catabolic niche, with significant downregulation of matrix degrading factors, ADAMTS5 and MMP13 and pro\u2010inflammatory cytokines, TNF and IL\u20101\u03b2. Furthermore, delivery of dual\u2010miRNA stimulated nucleus pulposus cells in an organ culture model of mild IVD degeneration significantly upregulated the matrix markers, SOX9 and aggrecan. However, this matrix response was not identified in dual\u2010miRNA\u2010bone marrow derived stem cells delivered to goat IVD organs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Taken together, these findings highlight the potential of nucleus pulposus cells as a regenerative cell source when combined with FLR\u2010miRNA\u2010149\u20105p mimic and 221\u20103p inhibitor for the treatment of LBP.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jsp2.70198","type":"journal-article","created":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T04:14:21Z","timestamp":1780719261000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparative Analysis of Dual\u2010\n                    <scp>miRNA<\/scp>\n                    Mediated Stimulation of Nucleus Pulposus and Bone Marrow Derived Stem Cells for Intervertebral Disc Repair"],"prefix":"10.1002","volume":"9","author":[{"given":"Tara N\u00ed","family":"N\u00e9ill","sequence":"first","affiliation":[{"name":"Trinity Centre for Biomedical Engineering, Trinity Biomedical Sciences Institute Trinity College Dublin, The University of Dublin  Dublin Ireland"},{"name":"Discipline of Mechanical, Manufacturing and Biomedical Engineering, School of Engineering, Trinity College Dublin The University of Dublin  Dublin Ireland"},{"name":"Advanced Materials and Bioengineering Research (AMBER) Centre Royal College of Surgeons in Ireland &amp; 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Trinity College Dublin, The University of Dublin  Dublin Ireland"},{"name":"National Spinal Injuries Unit Mater Misericordiae University Hospital  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2030-8005","authenticated-orcid":false,"given":"Fergal J.","family":"O'Brien","sequence":"additional","affiliation":[{"name":"Trinity Centre for Biomedical Engineering, Trinity Biomedical Sciences Institute Trinity College Dublin, The University of Dublin  Dublin Ireland"},{"name":"Discipline of Mechanical, Manufacturing and Biomedical Engineering, School of Engineering, Trinity College Dublin The University of Dublin  Dublin Ireland"},{"name":"Advanced Materials and Bioengineering Research (AMBER) Centre Royal College of Surgeons in Ireland &amp; Trinity College Dublin, The University of Dublin  Dublin Ireland"},{"name":"Tissue Engineering Research Group, Department of Anatomy and Regenerative Medicine RCSI  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline M.","family":"Curtin","sequence":"additional","affiliation":[{"name":"Trinity Centre for Biomedical Engineering, Trinity Biomedical Sciences Institute Trinity College Dublin, The University of Dublin  Dublin Ireland"},{"name":"Discipline of Mechanical, Manufacturing and Biomedical Engineering, School of Engineering, Trinity College Dublin The University of Dublin  Dublin Ireland"},{"name":"Advanced Materials and Bioengineering Research (AMBER) Centre Royal College of Surgeons in Ireland &amp; 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