{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T15:11:01Z","timestamp":1778598661175,"version":"3.51.4"},"reference-count":85,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Grants-in-Aid for Challenging Research","award":["15K15759"],"award-info":[{"award-number":["15K15759"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Cell Transplant"],"published-print":{"date-parts":[[2021,1,1]]},"abstract":"<jats:p>Cleft lip and palate is a congenital disorder including cleft lip, and\/or cleft palate, and\/or alveolar cleft, with high incidence.The alveolar cleft causes morphological and functional abnormalities. To obtain bone bridge formation and continuous structure between alveolar clefts, surgical interventions are performed from infancy to childhood. However, desirable bone bridge formation is not obtained in many cases. Regenerative medicine using mesenchymal stem cells (MSCs) is expected to be a useful strategy to obtain sufficient bone bridge formation between alveolar clefts. In this study, we examined the effect of human umbilical cord-derived MSCs by transplantation into a rat experimental alveolar cleft model. Human umbilical cords were digested enzymatically and the isolated cells were collected (UC-EZ cells). Next, CD146-positive cells were enriched from UC-EZ cells by magnetic-activated cell sorting (UC-MACS cells). UC-EZ and UC-MACS cells showed MSC gene\/protein expression, in vitro. Both cells had multipotency and could differentiate to osteogenic, chondrogenic, and adipogenic lineages under the differentiation-inducing media. However, UC-EZ cells lacked Sox2 expression and showed the lower ratio of MSCs than UC-MACS cells. Thus, UC-MACS cells were transplanted with hydroxyapatite and collagen (HA + Col) into alveolar cleft model to evaluate bone formation in vivo. The results of micro computed tomography and histological staining showed that UC-MACS cells with HA + Col induced more abundant bone formation between the experimental alveolar clefts than HA + Col implantation only. Cells immunopositive for osteopontin were accumulated along the bone surface and some of them were embedded in the bone. Cells immunopositive for human-specific mitochondria were aligned along the newly formed bone surface and in the new bone, suggesting that UC-MACS cells contributed to the bone bridge formation between alveolar clefts. These findings indicate that human umbilical cords are reliable bioresource and UC-MACS cells are useful for the alveolar cleft regeneration.<\/jats:p>","DOI":"10.1177\/0963689720975391","type":"journal-article","created":{"date-parts":[[2021,2,13]],"date-time":"2021-02-13T07:27:44Z","timestamp":1613201264000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":25,"title":["Regeneration in Experimental Alveolar Bone Defect Using Human Umbilical Cord Mesenchymal Stem Cells"],"prefix":"10.1177","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8999-0607","authenticated-orcid":false,"given":"Akiko","family":"Toyota","sequence":"first","affiliation":[{"name":"Division of Orthodontics, Department of Human Development and Fostering, Meikai University School of Dentistry, Saitama, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rei","family":"Shinagawa","sequence":"additional","affiliation":[{"name":"Division of Orthodontics, Department of Human Development and Fostering, Meikai University School of Dentistry, Saitama, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikiko","family":"Mano","sequence":"additional","affiliation":[{"name":"Division of Orthodontics, Department of Human Development and Fostering, Meikai University School of Dentistry, Saitama, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuyuki","family":"Tokioka","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, Saitama Medical University, Saitama, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoto","family":"Suda","sequence":"additional","affiliation":[{"name":"Division of Orthodontics, Department of Human Development and Fostering, Meikai University School of Dentistry, Saitama, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2021,2,12]]},"reference":[{"key":"bibr1-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60695-4"},{"key":"bibr2-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2933"},{"key":"bibr3-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1177\/1055665618774019"},{"key":"bibr4-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-6343.2007.00398.x"},{"key":"bibr5-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajodo.2014.06.002"},{"issue":"7","key":"bibr6-0963689720975391","first-page":"11","volume":"98","author":"Panamonta V","year":"2015","journal-title":"J Med Assoc Thai"},{"key":"bibr7-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31447"},{"key":"bibr8-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcms.2015.02.019"},{"key":"bibr9-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajoms.2013.04.017"},{"key":"bibr10-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/583416"},{"key":"bibr11-0963689720975391","doi-asserted-by":"publisher","DOI":"10.5999\/aps.2017.44.3.202"},{"issue":"2","key":"bibr12-0963689720975391","first-page":"e2175","volume":"10","author":"Kalaiarasi R","year":"2018","journal-title":"Cureus"},{"key":"bibr13-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1097\/00006534-195904000-00003"},{"key":"bibr14-0963689720975391","first-page":"246","volume":"12","author":"Millard DR","year":"1964","journal-title":"Cleft Palate J"},{"key":"bibr15-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1097\/00000637-198006000-00012"},{"key":"bibr16-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1002\/bjs.1800259715"},{"key":"bibr17-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1097\/00006534-198678060-00002"},{"issue":"2","key":"bibr18-0963689720975391","first-page":"87","volume":"30","author":"Boyne PJ","year":"1972","journal-title":"J Oral Surg"},{"key":"bibr19-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9416(76)90258-X"},{"key":"bibr20-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1097\/00000637-198612000-00005"},{"key":"bibr21-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1597\/1545-1569_1995_032_0420_cwasab_2.3.co_2"},{"key":"bibr22-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1093\/ejo\/20.3.299"},{"key":"bibr23-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1097\/scs.0b013e31814e059b"},{"key":"bibr24-0963689720975391","doi-asserted-by":"publisher","DOI":"10.3109\/02844316709022841"},{"key":"bibr25-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1597\/1545-1569_2001_038_0193_pnomip_2.0.co_2"},{"key":"bibr26-0963689720975391","first-page":"1309","volume-title":"Comprehensive Cleft Care","author":"Hoppper RA","year":"2015"},{"issue":"3","key":"bibr27-0963689720975391","first-page":"201","volume":"39","author":"Mano M","year":"2014","journal-title":"J Jpn Cleft Palate Assoc"},{"key":"bibr28-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1097\/01.prs.0000304604.89450.ae"},{"key":"bibr29-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1597\/1545-1569_1998_035_0077_rnfabg_2.3.co_2"},{"key":"bibr30-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1097\/01.prs.0000302461.56820.c9"},{"issue":"1","key":"bibr31-0963689720975391","first-page":"12","volume":"59","author":"Kawakami S","year":"2000","journal-title":"Orthodontic waves"},{"key":"bibr32-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1016\/j.oooo.2017.04.003"},{"key":"bibr33-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1053\/joms.2000.16623"},{"key":"bibr34-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1016\/j.bjoms.2007.12.010"},{"key":"bibr35-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5411.143"},{"key":"bibr36-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2005-0342"},{"key":"bibr37-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1007\/s10266-012-0075-0"},{"key":"bibr38-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2016.0330"},{"issue":"5","key":"bibr39-0963689720975391","first-page":"267","volume":"4","author":"Friedenstein AJ","year":"1976","journal-title":"Exp Hematol"},{"key":"bibr40-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1172\/JCI10413"},{"key":"bibr41-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.21200"},{"key":"bibr42-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.21-1-105"},{"key":"bibr43-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2007-1028"},{"issue":"5","key":"bibr44-0963689720975391","first-page":"5129","volume":"8","author":"Zhang J","year":"2015","journal-title":"Int J Clin Exp Pathol"},{"key":"bibr45-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0076153"},{"key":"bibr46-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2004-0013"},{"key":"bibr47-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1155\/2009\/789526"},{"key":"bibr48-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-60761-999-4_5"},{"key":"bibr49-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2005-0546"},{"key":"bibr50-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2006-0709"},{"key":"bibr51-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-010-0665-2"},{"issue":"3","key":"bibr52-0963689720975391","doi-asserted-by":"crossref","first-page":"e0120593","DOI":"10.1371\/journal.pone.0120593","volume":"10","author":"Wang KX","year":"2015","journal-title":"PLoS One"},{"key":"bibr53-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1177\/1535370214539225"},{"issue":"10","key":"bibr54-0963689720975391","doi-asserted-by":"crossref","first-page":"e0122465","DOI":"10.1371\/journal.pone.0122465","volume":"10","author":"Ali H","year":"2015","journal-title":"PLoS One"},{"key":"bibr55-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1016\/j.jos.2016.01.007"},{"key":"bibr56-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1097\/PRS.0b013e3181bf8024"},{"key":"bibr57-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcms.2014.07.001"},{"key":"bibr58-0963689720975391","doi-asserted-by":"publisher","DOI":"10.4252\/wjsc.v6.i2.195"},{"key":"bibr59-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1093\/ejo\/cjs060"},{"key":"bibr60-0963689720975391","doi-asserted-by":"publisher","DOI":"10.4103\/ijps.IJPS_84_18"},{"key":"bibr61-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1590\/1679-775720130127"},{"key":"bibr62-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199708073370602"},{"key":"bibr63-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2008.02891.x"},{"key":"bibr64-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9896(199909)189:1<4::AID-PATH332>3.0.CO;2-P"},{"key":"bibr65-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2008.03.004"},{"key":"bibr66-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2003.18.4.696"},{"key":"bibr67-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.08.025"},{"key":"bibr68-0963689720975391","doi-asserted-by":"publisher","DOI":"10.4161\/cc.11.2.18858"},{"key":"bibr69-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1002\/stem.312"},{"key":"bibr70-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1007\/s10439-013-0807-5"},{"key":"bibr71-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0213374"},{"key":"bibr72-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2014.11.024"},{"key":"bibr73-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.11.019"},{"key":"bibr74-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1186\/1477-7827-4-8"},{"key":"bibr75-0963689720975391","doi-asserted-by":"publisher","DOI":"10.5966\/sctm.2015-0109"},{"key":"bibr76-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1038\/srep12721"},{"key":"bibr77-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-017-0592-4"},{"key":"bibr78-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2015.02.011"},{"key":"bibr79-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2016.10.039"},{"key":"bibr80-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2012.113"},{"issue":"1","key":"bibr81-0963689720975391","first-page":"91","volume":"55","author":"Tsuchiya A","year":"2008","journal-title":"J Med Dent Sci"},{"key":"bibr82-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2013.09.002"},{"key":"bibr83-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.b.33814"},{"key":"bibr84-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/4258613"},{"key":"bibr85-0963689720975391","doi-asserted-by":"publisher","DOI":"10.1210\/er.2012-1026"}],"container-title":["Cell Transplantation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0963689720975391","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/0963689720975391","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0963689720975391","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T15:38:35Z","timestamp":1777390715000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/0963689720975391"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,1]]},"references-count":85,"alternative-id":["10.1177\/0963689720975391"],"URL":"https:\/\/doi.org\/10.1177\/0963689720975391","relation":{},"ISSN":["0963-6897","1555-3892"],"issn-type":[{"value":"0963-6897","type":"print"},{"value":"1555-3892","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,1]]},"article-number":"0963689720975391"}}