{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:36:52Z","timestamp":1787027812840,"version":"build-2736575974"},"reference-count":48,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T00:00:00Z","timestamp":1675382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education, Culture, Sports, Science, and Technology of Japan","award":["20K17983"],"award-info":[{"award-number":["20K17983"]}]},{"name":"Ministry of Education, Culture, Sports, Science, and Technology of Japan","award":["21H03313"],"award-info":[{"award-number":["21H03313"]}]},{"name":"Ministry of Education, Culture, Sports, Science, and Technology of Japan","award":["JP22bk0104143h0001"],"award-info":[{"award-number":["JP22bk0104143h0001"]}]},{"DOI":"10.13039\/100009619","name":"Project for Regenerative\/Cellular Medicine and Gene Therapies at the Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["20K17983"],"award-info":[{"award-number":["20K17983"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Project for Regenerative\/Cellular Medicine and Gene Therapies at the Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["21H03313"],"award-info":[{"award-number":["21H03313"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Project for Regenerative\/Cellular Medicine and Gene Therapies at the Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP22bk0104143h0001"],"award-info":[{"award-number":["JP22bk0104143h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Intervertebral disc (IVD) degeneration is a major cause of low back pain. However, treatments directly approaching the etiology of IVD degeneration and discogenic pain are not yet established. We previously demonstrated that intradiscal implantation of cell-free bioresorbable ultra-purified alginate (UPAL) gel promotes tissue repair and reduces discogenic pain, and a combination of ultra-purified, Good Manufacturing Practice (GMP)-compliant, human bone marrow mesenchymal stem cells (rapidly expanding clones; RECs), and the UPAL gel increasingly enhanced IVD regeneration in animal models. This study investigated the therapeutic efficacy of injecting a mixture of REC and UPAL non-gelling solution for discogenic pain and IVD regeneration in a rat caudal nucleus pulposus punch model. REC and UPAL mixture and UPAL alone suppressed not only the expression of TNF-\u03b1, IL-6, and TrkA (p &lt; 0.01, respectively), but also IVD degeneration and nociceptive behavior compared to punching alone (p &lt; 0.01, respectively). Furthermore, REC and UPAL mixture suppressed these expression levels and nociceptive behavior compared to UPAL alone (p &lt; 0.01, respectively). These results suggest that this minimally invasive treatment strategy with a single injection may be applied to treat discogenic pain and as a regenerative therapy.<\/jats:p>","DOI":"10.3390\/cells12030505","type":"journal-article","created":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T05:09:20Z","timestamp":1675400960000},"page":"505","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Injection of Ultra-Purified Stem Cells with Sodium Alginate Reduces Discogenic Pain in a Rat Model"],"prefix":"10.3390","volume":"12","author":[{"given":"Hisataka","family":"Suzuki","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, N15W7, Sapporo 060-8638, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4816-0807","authenticated-orcid":false,"given":"Katsuro","family":"Ura","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, N15W7, Sapporo 060-8638, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Ukeba","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, N15W7, Sapporo 060-8638, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Suyama","sequence":"additional","affiliation":[{"name":"PuREC\/Bio-Venture, Shimane University, Izumo 693-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5496-4046","authenticated-orcid":false,"given":"Norimasa","family":"Iwasaki","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, N15W7, Sapporo 060-8638, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masatoki","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Japan Tissue Engineering Co., Ltd. (J-TEC), Gamagori 443-0022, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumi","family":"Matsuzaki","sequence":"additional","affiliation":[{"name":"PuREC\/Bio-Venture, Shimane University, Izumo 693-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9841-5890","authenticated-orcid":false,"given":"Katsuhisa","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, N15W7, Sapporo 060-8638, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8635-4648","authenticated-orcid":false,"given":"Hideki","family":"Sudo","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, N15W7, Sapporo 060-8638, Japan"},{"name":"Department of Advanced Medicine for Spine and Spinal Cord Disorders, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, N15W7, Sapporo 060-8638, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1136\/annrheumdis-2013-204428","article-title":"The global burden of low back pain: Estimates from the Global Burden of Disease 2010 study","volume":"73","author":"Hoy","year":"2014","journal-title":"Ann. 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