{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:52:50Z","timestamp":1790841170367,"version":"4.1.0"},"reference-count":95,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,4,22]],"date-time":"2018-04-22T00:00:00Z","timestamp":1524355200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Bright Sparks Funding, Vetmeduni Vienna, Austria","award":["PP10014701"],"award-info":[{"award-number":["PP10014701"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>A combination of tissue engineering methods employing mesenchymal stem cells (MSCs) together with gene transfer takes advantage of innovative strategies and highlights a new approach for targeting osteoarthritis (OA) and other cartilage defects. Furthermore, the development of systems allowing tunable transgene expression as regulated by natural disease\u2010induced substances is highly desirable.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Bone marrow\u2010derived equine MSCs were transduced with a lentiviral vector expressing interleukin\u20101 receptor antagonist (IL\u20101Ra) gene under the control of an inducible nuclear factor\u2010kappa B\u2010responsive promoter and IL\u20101Ra production upon pro\u2010inflammatory cytokine stimulation [tumor necrosis factor (TNF)\u03b1, interleukin (IL)\u20101\u03b2] was analysed. To assess the biological activity of the IL\u20101Ra protein that was produced and the therapeutic effect of IL\u20101Ra\u2010expressing MSCs (MSC\/IL\u20101Ra), cytokine\u2010based two\u2010 and three\u2010dimensional\n                      <jats:italic>in vitro<\/jats:italic>\n                      models of osteoarthritis using equine chondrocytes were established and quantitative real\u2010time polymerase chain reaction (PCR) analysis was used to measure the gene expression of aggrecan, collagen IIA1, interleukin\u20101\u03b2, interleukin\u20106, interleukin\u20108, matrix metalloproteinase\u20101 and matrix metalloproteinase\u201013.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A dose\u2010dependent increase in IL\u20101Ra expression was found in MSC\/IL\u20101Ra cells upon TNF\u03b1 administration, whereas stimulation using IL\u20101\u03b2 did not lead to IL\u20101Ra production above the basal level observed in nonstimulated cells as a result of the existing feedback loop. Repeated cycles of induction allowed on\/off modulation of transgene expression.\n                      <jats:italic>In vitro<\/jats:italic>\n                      analyses revealed that IL\u20101Ra protein present in the conditioned medium from MSC\/IL\u20101Ra cells blocks OA onset in cytokine\u2010treated equine chondrocytes and co\u2010cultivation of MSC\/IL\u20101Ra cells with osteoarthritic spheroids alleviates the severity of the osteoarthritic changes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Thus, pro\u2010inflammatory cytokine induced IL\u20101Ra protein expression from genetically modified MSCs might represent a promising strategy for osteoarthritis treatment.<\/jats:p>\n                  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