{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T21:31:35Z","timestamp":1767648695272},"reference-count":23,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JNS"],"published-print":{"date-parts":[[2012,10]]},"abstract":"<jats:sec>\n<jats:title>Object<\/jats:title>\n<jats:p>CD133<jats:sup>+<\/jats:sup> cells have the potential to enhance histological and functional recovery from peripheral nerve injury. However, the number of CD133<jats:sup>+<\/jats:sup> cells safely obtained from human peripheral blood is extremely limited. To address this issue, the authors expanded CD133<jats:sup>+<\/jats:sup> cells derived from human peripheral blood using the serum-free expansion culture method and transplanted these ex vivo expanded cells into a model of sciatic nerve defect in rats. The purpose of this study was to determine the potential of ex vivo expanded CD133<jats:sup>+<\/jats:sup> cells to induce or enhance the repair of injured peripheral nerves.<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Phosphate-buffered saline (PBS group [Group 1]), 10<jats:sup>5<\/jats:sup> fresh CD133<jats:sup>+<\/jats:sup> cells (fresh group [Group 2]), 10<jats:sup>5<\/jats:sup> ex vivo expanded CD133<jats:sup>+<\/jats:sup> cells (expansion group [Group 3]), or 10<jats:sup>4<\/jats:sup> fresh CD133<jats:sup>+<\/jats:sup> cells (low-dose group [Group 4]) embedded in atelocollagen gel were transplanted into a silicone tube that was then used to bridge a 15-mm defect in the sciatic nerve of athymic rats (10 animals per group). At 8 weeks postsurgery, histological and functional evaluations of the regenerated tissues were performed.<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>After 1 week of expansion culture, the number of cells increased 9.6 \u00b1 3.3\u2013fold. Based on the fluorescence-activated cell sorting analysis, it was demonstrated that the initial freshly isolated CD133<jats:sup>+<\/jats:sup> cell population contained 93.22% \u00b1 0.30% CD133<jats:sup>+<\/jats:sup> cells and further confirmed that the expanded cells had a purity of 59.02% \u00b1 1.58% CD133<jats:sup>+<\/jats:sup> cells. However, the histologically and functionally regenerated nerves bridging the defects were recognized in all rats in Groups 2 and 3 and in 6 of 10 rats in Group 4. The nerves did not regenerate to bridge the defect in any of the rats in Group 1.<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>The authors' results show that ex vivo expanded CD133<jats:sup>+<\/jats:sup> cells derived from human peripheral blood have a therapeutic potential similar to fresh CD133<jats:sup>+<\/jats:sup> cells for peripheral nerve injuries. The ex vivo procedure that can be used to expand CD133<jats:sup>+<\/jats:sup> cells without reducing their function represents a novel method for developing cell therapy for nerve defects in a clinical setting.<\/jats:p><\/jats:sec>","DOI":"10.3171\/2012.7.jns111503","type":"journal-article","created":{"date-parts":[[2012,8,10]],"date-time":"2012-08-10T13:56:55Z","timestamp":1344607015000},"page":"787-794","source":"Crossref","is-referenced-by-count":9,"title":["The therapeutic potential of ex vivo expanded CD133+ cells derived from human peripheral blood for peripheral nerve injuries"],"prefix":"10.3171","volume":"117","author":[{"given":"Shin","family":"Ohtsubo","sequence":"first","affiliation":[{"name":"Departments of Orthopaedic Surgery and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masakazu","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"Departments of Orthopaedic Surgery and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naosuke","family":"Kamei","sequence":"additional","affiliation":[{"name":"Departments of Orthopaedic Surgery and"},{"name":"Division of Regeneration and Medicine, Hiroshima University Hospital;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasumu","family":"Kijima","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Sera Central Hospital, Hiroshima;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Osami","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Departments of Orthopaedic Surgery and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toru","family":"Sunagawa","sequence":"additional","affiliation":[{"name":"Anatomy and Histology, Graduate School of Biomedical Sciences, Hiroshima University;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukihito","family":"Higashi","sequence":"additional","affiliation":[{"name":"Division of Regeneration and Medicine, Hiroshima University Hospital;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haruchika","family":"Masuda","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Science, Tokai University School of Medicine, Isehara; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takayuki","family":"Asahara","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Science, Tokai University School of Medicine, Isehara; and"},{"name":"Group of Vascular Regeneration, Institute of Biomedical Research and Innovation, Kobe, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitsuo","family":"Ochi","sequence":"additional","affiliation":[{"name":"Departments of Orthopaedic Surgery and"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1754","reference":[{"key":"b1-jns111503","series-title":"Science","first-page":"964","article-title":"Isolation of putative progenitor endothelial cells for angiogenesis","volume":"275","author":"Asahara","year":"1997"},{"key":"b2-jns111503","series-title":"J Reconstr Microsurg","first-page":"439","article-title":"Effect of Schwann cells in the enhancement of peripheral-nerve regeneration","volume":"12","author":"Bryan","year":"1996"},{"key":"b3-jns111503","series-title":"Ann Neurol","first-page":"32","article-title":"Recovery from paralysis in adult rats using embryonic stem cells","volume":"60","author":"Deshpande","year":"2006"},{"key":"b4-jns111503","series-title":"J Hematother Stem Cell Res","first-page":"827","article-title":"A functional hierarchy among the CD34+ hematopoietic cells based on in vitro proliferative and differentiative potential of AC133+CD34(bright) and AC133(dim\/)-CD34+ human cord blood cells","volume":"9","author":"Goussetis","year":"2000"},{"key":"b5-jns111503","series-title":"Microsurgery","first-page":"96","article-title":"A new artificial nerve graft containing rolled Schwann cell monolayers","volume":"21","author":"Hadlock","year":"2001"},{"key":"b6-jns111503","series-title":"J Am Coll Cardiol","first-page":"1441","article-title":"Impaired progenitor cell activity in age-related endothelial dysfunction","volume":"45","author":"Heiss","year":"2005"},{"key":"b7-jns111503","series-title":"Circulation","first-page":"1311","article-title":"Dose-dependent contribution of CD34-positive cell transplantation to concurrent vasculogenesis and cardiomyogenesis for functional regenerative recovery after myocardial infarction","volume":"113","author":"Iwasaki","year":"2006"},{"key":"b8-jns111503","series-title":"Stem Cells","first-page":"2857","article-title":"Intramuscular transplantation of G-CSFmobilized CD34+ cells in patients with critical limb ischemia: a phase I\/IIa, multicenter, single-blinded, dose-escalation clinical trial","volume":"27","author":"Kawamoto","year":"2009"},{"key":"b9-jns111503","series-title":"J Neurosurg","first-page":"758","article-title":"Regeneration of peripheral nerve after transplantation of CD133+ cells derived from human peripheral blood. Laboratory investigation","volume":"110","author":"Kijima","year":"2009"},{"key":"b10-jns111503","series-title":"Stem Cells Dev","first-page":"229","article-title":"Identification of the adult human hemangioblast","volume":"13","author":"Loges","year":"2004"},{"key":"b11-jns111503","series-title":"Plast Reconstr Surg","first-page":"419","article-title":"Clinical nerve reconstruction with a bioabsorbable polyglycolic acid tube","volume":"85","author":"Mackinnon","year":"1990"},{"key":"b12-jns111503","series-title":"Blood","first-page":"3075","article-title":"Numerous growth factors, cytokines, and chemokines are secreted by human CD34+ cells, myeloblasts, erythroblasts, and megakaryoblasts and regulate normal hematopoiesis in an autocrine\/paracrine manner","volume":"97","author":"Majka","year":"2001"},{"key":"b13-jns111503","series-title":"Stem Cells Trans Med","article-title":"Development of serum-free quality and quantity control culture of colony forming endothelial progenitor cell expansion for vasculogenesis","author":"Masuda","year":"2012"},{"key":"b14-jns111503","series-title":"Am J Pathol","first-page":"1440","article-title":"Therapeutic potential of vasculogenesis and osteogenesis promoted by peripheral blood CD34-positive cells for functional bone healing","volume":"169","author":"Matsumoto","year":"2006"},{"key":"b15-jns111503","series-title":"Brain Res","first-page":"17","article-title":"Transplanted neuronal progenitor cells in a peripheral nerve gap promote nerve repair","volume":"974","author":"Murakami","year":"2003"},{"key":"b16-jns111503","series-title":"Blood","first-page":"952","article-title":"Expression of VEGFR-2 and AC133 by circulating human CD34+ cells identifies a population of functional endothelial precursors","volume":"95","author":"Peichev","year":"2000"},{"key":"b17-jns111503","series-title":"Nat Med","first-page":"702","article-title":"Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration","volume":"9","author":"Rafii","year":"2003"},{"key":"b18-jns111503","series-title":"Neurosci Lett","first-page":"200","article-title":"Rat bone marrow mesenchymal stem cells express glial markers and stimulate nerve regeneration","volume":"362","author":"Tohill","year":"2004"},{"key":"b19-jns111503","series-title":"Trends Cardiovasc Med","first-page":"318","article-title":"Endothelial progenitor cells functional characterization","volume":"14","author":"Urbich","year":"2004"},{"key":"b20-jns111503","series-title":"Circ Res","first-page":"E1","article-title":"Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease","volume":"89","author":"Vasa","year":"2001"},{"key":"b21-jns111503","series-title":"Exp Neurol","first-page":"251","article-title":"Neurogenesis in the ependymal layer of the adult rat 3rd ventricle","volume":"192","author":"Xu","year":"2005"},{"key":"b22-jns111503","series-title":"Chin J Traumatol","first-page":"77","article-title":"Differentiation of adult human bone marrow mesenchymal stem cells into Schwannlike cells in vitro","volume":"8","author":"Yang","year":"2005"},{"key":"b23-jns111503","series-title":"Blood","first-page":"5002","article-title":"AC133, a novel marker for human hematopoietic stem and progenitor cells","volume":"90","author":"Yin","year":"1997"}],"container-title":["Journal of Neurosurgery"],"original-title":[],"link":[{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg\/117\/4\/article-p787.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg\/117\/4\/article-p787.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg\/117\/4\/article-p787.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,26]],"date-time":"2023-03-26T23:39:56Z","timestamp":1679873996000},"score":1,"resource":{"primary":{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg\/117\/4\/article-p787.xml"}},"subtitle":["Laboratory investigation"],"short-title":[],"issued":{"date-parts":[[2012,10]]},"references-count":23,"journal-issue":{"issue":"4"},"URL":"https:\/\/doi.org\/10.3171\/2012.7.jns111503","relation":{},"ISSN":["0022-3085","1933-0693"],"issn-type":[{"value":"0022-3085","type":"print"},{"value":"1933-0693","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,10]]}}}