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We utilized an ovine IVDD model and intradiscal heterologous MSCs to determine therapeutic efficacy at different stages of IVDD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methodology<\/jats:title><jats:p>Three nonoperated control (NOC) sheep were used for MSC isolation. In 36 sheep, 6\u2009\u00d7\u200920\u2009mm annular lesions were made at three spinal levels using customized blades\/scalpel handles, and IVDD was allowed to develop for 4 weeks in the Early (EA) and late Acute (LA) groups, or 12\u2009weeks in the chronic (EST) group. Lesion IVDs received injections of 10\u2009\u00d7\u200910<jats:sup>6<\/jats:sup>MSCs or PBS, and after 8 (EA), 22 (LA) or 14 (EST) weeks recuperation the sheep were sacrificed. Longitudinal lateral radiographs were used to determine disc heights. IVD glycosaminoglycan (GAG) and hydroxyproline contents were quantified using established methods. An Instron materials testing machine and customized jigs analyzed IVD (range of motion, neutral zone [NZ] and stiffness) in flexion\/extension, lateral bending and axial rotation. qRTPCR gene profiles of key anabolic and catabolic matrix molecules were undertaken. Toluidine blue and hematoxylin and eosin stained IVD sections were histopathologically scoring by two blinded observers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>IVDD significantly reduced disc heights. MSC treatment restored 95% to 100% of disc height, maximally improved NZ and stiffness in flexion\/extension and lateral bending in the EST group, restoring GAG levels. With IVDD qRTPCR demonstrated elevated catabolic gene expression (<jats:italic>MMP2\/3\/9\/13, ADAMTS4\/5<\/jats:italic>) in the PBS IVDs and expession normalization in MSC\u2010treated IVDs. Histopathology degeneracy scores were close to levels of NOC IVDs in MSC IVDs but IVDD developed in PBS injected IVDs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Administered MSCs produced recovery in degenerate IVDs, restored disc height, composition, biomechanical properties, down regulated MMPs and fibrosis, strongly supporting the efficacy of MSCs for disc repair.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jsp2.1037","type":"journal-article","created":{"date-parts":[[2018,9,18]],"date-time":"2018-09-18T07:49:35Z","timestamp":1537256975000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Efficacy of administered mesenchymal stem cells in the initiation and co\u2010ordination of repair processes by resident disc cells in an ovine (<scp><i>Ovis aries<\/i><\/scp>) large destabilizing lesion model of experimental disc degeneration"],"prefix":"10.1002","volume":"1","author":[{"given":"Cindy C.","family":"Shu","sequence":"first","affiliation":[{"name":"Raymond Purves Bone and Joint Research Laboratory, Kolling Institute, Northern Sydney Local Health District St. Leonards New South Wales Australia"},{"name":"Faculty of Medicine and Health University of Sydney, Royal North Shore Hospital St. Leonards New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Dart","sequence":"additional","affiliation":[{"name":"University of SydneyVeterinary Teaching Hospital Camden New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Bell","sequence":"additional","affiliation":[{"name":"University of SydneyVeterinary Teaching Hospital Camden New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Dart","sequence":"additional","affiliation":[{"name":"University 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