{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T21:36:09Z","timestamp":1789940169084,"version":"4.0.1"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2015,2,4]],"date-time":"2015-02-04T00:00:00Z","timestamp":1423008000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,7,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>\u2003<\/jats:title>\n                  <jats:p>Bone engineering of localized craniofacial osseous defects or deficiencies by stem cell therapy offers strong prospects to improve treatment predictability for patient care. The aim of this phase 1\/2 randomized, controlled clinical trial was to evaluate reconstruction of bone deficiencies of the maxillary sinus with transplantation of autologous cells enriched with CD90+ stem cells and CD14+ monocytes. Thirty human participants requiring bone augmentation of the maxillary sinus were enrolled. Patients presenting with 50% to 80% bone deficiencies of the maxillary sinus were randomized to receive either stem cells delivered onto a \u03b2-tricalcium phosphate scaffold or scaffold alone. Four months after treatment, clinical, radiographic, and histologic analyses were performed to evaluate de novo engineered bone. At the time of alveolar bone core harvest, oral implants were installed in the engineered bone and later functionally restored with dental tooth prostheses. Radiographic analyses showed no difference in the total bone volume gained between treatment groups; however, density of the engineered bone was higher in patients receiving stem cells. Bone core biopsies showed that stem cell therapy provided the greatest benefit in the most severe deficiencies, yielding better bone quality than control patients, as evidenced by higher bone volume fraction (BVF; 0.5 versus 0.4; p\u2009=\u20090.04). Assessment of the relation between degree of CD90+ stem cell enrichment and BVF showed that the higher the CD90 composition of transplanted cells, the greater the BVF of regenerated bone (r\u2009=\u20090.56; p\u2009=\u20090.05). Oral implants were placed and restored with functionally loaded dental restorations in all patients and no treatment-related adverse events were reported at the 1-year follow-up. These results provide evidence that cell-based therapy using enriched CD90+ stem cell populations is safe for maxillary sinus floor reconstruction and offers potential to accelerate and enhance tissue engineered bone quality in other craniofacial bone defects and deficiencies (Clinicaltrials.gov NCT00980278). \u00a9 2015 American Society for Bone and Mineral Research. \u00a9 2015 American Society for Bone and Mineral Research<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/jbmr.2464","type":"journal-article","created":{"date-parts":[[2015,2,4]],"date-time":"2015-02-04T21:09:34Z","timestamp":1423084174000},"page":"1206-1216","source":"Crossref","is-referenced-by-count":99,"title":["Bone Engineering of Maxillary Sinus Bone Deficiencies Using Enriched CD90+ Stem Cell Therapy: A Randomized Clinical Trial"],"prefix":"10.1093","volume":"30","author":[{"given":"Darnell","family":"Kaigler","sequence":"first","affiliation":[{"name":"Department of Biomedical EngineeringCollege of EngineeringUniversity of MichiganAnn ArborMIUSA"},{"name":"Center for Oral Health ResearchAnn ArborMIUSA"},{"name":"Department of Periodontics and Oral MedicineUniversity of Michigan School of DentistryAnn ArborMIUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo","family":"Avila-Ortiz","sequence":"additional","affiliation":[{"name":"Department of Periodontics and Oral MedicineUniversity of Michigan School of DentistryAnn ArborMIUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suncica","family":"Travan","sequence":"additional","affiliation":[{"name":"Center for Oral Health ResearchAnn ArborMIUSA"},{"name":"Department of Periodontics and Oral MedicineUniversity of Michigan School of DentistryAnn ArborMIUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrei D","family":"Taut","sequence":"additional","affiliation":[{"name":"Department of Periodontics and Oral MedicineUniversity of Michigan School of DentistryAnn ArborMIUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Padial-Molina","sequence":"additional","affiliation":[{"name":"Department of Periodontics and Oral MedicineUniversity of Michigan School of DentistryAnn ArborMIUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Rudek","sequence":"additional","affiliation":[{"name":"Department of Periodontics and Oral MedicineUniversity of Michigan School of DentistryAnn ArborMIUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Oral Health ResearchAnn ArborMIUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Lanis","sequence":"additional","affiliation":[{"name":"Center for Oral Health ResearchAnn ArborMIUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William V","family":"Giannobile","sequence":"additional","affiliation":[{"name":"Department of Biomedical EngineeringCollege of EngineeringUniversity of MichiganAnn ArborMIUSA"},{"name":"Center for Oral Health ResearchAnn ArborMIUSA"},{"name":"Department of Periodontics and Oral MedicineUniversity of Michigan School of DentistryAnn ArborMIUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,2,4]]},"reference":[{"issue":"5","key":"2024020319050762100_jbmr2464-bib-0001","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1542\/pir.35.5.177","article-title":"Cleft lip palate","volume":"35","author":"Abbott","year":"2014","journal-title":"Pediatr Rev."},{"issue":"5","key":"2024020319050762100_jbmr2464-bib-0002","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1111\/j.1600-051X.2005.00692.x","article-title":"Healing of extraction sockets and surgically produced\u2014augmented and non-augmented\u2014defects in the alveolar ridge. An experimental study in the dog","volume":"32","author":"Cardaropoli","year":"2005","journal-title":"J Clin Periodontol"},{"issue":"1","key":"2024020319050762100_jbmr2464-bib-0003","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1097\/ID.0b013e3182435ffd","article-title":"Augmentation of the anterior maxilla with intraoral onlay grafts for implant placement","volume":"21","author":"Greenberg","year":"2012","journal-title":"Implant Dent."},{"issue":"5","key":"2024020319050762100_jbmr2464-bib-0004","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1902\/jop.2005.76.5.821","article-title":"Treatment options following single-rooted tooth removal: a literature review and proposed hierarchy of treatment selection","volume":"76","author":"Fugazzotto","year":"2005","journal-title":"J Periodontol."},{"issue":"Suppl","key":"2024020319050762100_jbmr2464-bib-0005","first-page":"43","article-title":"Bone quantity and quality: are they relevant predictors of implant outcomes?","volume":"16","author":"Stanford","year":"2003","journal-title":"Int J Prosthodont."},{"key":"2024020319050762100_jbmr2464-bib-0006","first-page":"CD003607","article-title":"Interventions for replacing missing teeth: bone augmentation techniques for dental implant treatment","volume":"3","author":"Esposito","year":"2008","journal-title":"Cochrane Database Syst Rev."},{"issue":"3","key":"2024020319050762100_jbmr2464-bib-0007","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1902\/jop.2007.060048","article-title":"Bone augmentation techniques","volume":"78","author":"McAllister","year":"2007","journal-title":"J Periodontol."},{"issue":"21","key":"2024020319050762100_jbmr2464-bib-0008","doi-asserted-by":"crossref","first-page":"3053","DOI":"10.1016\/j.biomaterials.2008.03.012","article-title":"Cell based bone tissue engineering in jaw defects","volume":"29","author":"Meijer","year":"2008","journal-title":"Biomaterials."},{"issue":"1","key":"2024020319050762100_jbmr2464-bib-0009","first-page":"153","article-title":"Use of corticocancellous allogeneic bone blocks for augmentation of alveolar bone defects","volume":"25","author":"Peleg","year":"2010","journal-title":"Int J Oral Maxillofac Implants."},{"issue":"11","key":"2024020319050762100_jbmr2464-bib-0010","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1177\/154405910608501101","article-title":"Craniofacial tissue engineering by stem cells","volume":"85","author":"Mao","year":"2006","journal-title":"J Dent Res."},{"issue":"2","key":"2024020319050762100_jbmr2464-bib-0011","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1002\/jcp.21200","article-title":"Adult mesenchymal stem cells for tissue engineering versus regenerative medicine","volume":"213","author":"Caplan","year":"2007","journal-title":"J Cell Physiol."},{"issue":"9655","key":"2024020319050762100_jbmr2464-bib-0012","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1016\/S0140-6736(08)61598-6","article-title":"Clinical transplantation of a tissue-engineered airway","volume":"372","author":"Macchiarini","year":"2008","journal-title":"Lancet."},{"issue":"5","key":"2024020319050762100_jbmr2464-bib-0013","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1056\/NEJM200102013440516","article-title":"Repair of large bone defects with the use of autologous bone marrow stromal cells","volume":"344","author":"Quarto","year":"2001","journal-title":"N Engl J Med."},{"issue":"5","key":"2024020319050762100_jbmr2464-bib-0014","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1002\/stem.416","article-title":"Concise review: mind the gap: challenges in characterizing and quantifying cell- and tissue-based therapies for clinical translation","volume":"28","author":"Rayment","year":"2010","journal-title":"Stem Cells."},{"issue":"4","key":"2024020319050762100_jbmr2464-bib-0015","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1097\/scs.0b013e3180a771af","article-title":"Repair of alveolar cleft defects: reduced morbidity with bone marrow stem cells in a resorbable matrix","volume":"18","author":"Gimbel","year":"2007","journal-title":"J Craniofac Surg."},{"issue":"4","key":"2024020319050762100_jbmr2464-bib-0016","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1902\/jop.2009.080345","article-title":"Histologic evaluation of a stem cell-based sinus-augmentation procedure","volume":"80","author":"McAllister","year":"2009","journal-title":"J Periodontol."},{"issue":"4","key":"2024020319050762100_jbmr2464-bib-0017","doi-asserted-by":"crossref","first-page":"530","DOI":"10.5966\/sctm.2013-0173","article-title":"Adipose stem cells used to reconstruct 13 cases with cranio-maxillofacial hard-tissue defects","volume":"3","author":"Sandor","year":"2014","journal-title":"Stem Cells Transl Med."},{"issue":"5","key":"2024020319050762100_jbmr2464-bib-0018","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1097\/PRS.0b013e3181f24164","article-title":"Regenerative facial reconstruction of terminal stage osteoradionecrosis and other advanced craniofacial diseases with adult cultured stem and progenitor cells","volume":"126","author":"Mendonca","year":"2011","journal-title":"Plast Reconstr Surg."},{"issue":"4","key":"2024020319050762100_jbmr2464-bib-0019","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1097\/SCS.0b013e318294288a","article-title":"Reconstruction of human mandibular continuity defects with allogenic scaffold and autologous marrow mesenchymal stem cells","volume":"24","author":"Zamiri","year":"2013","journal-title":"J Craniofac Surg."},{"issue":"3","key":"2024020319050762100_jbmr2464-bib-0020","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1002\/stem.1300","article-title":"Injectable bone tissue engineering using expanded mesenchymal stem cells","volume":"31","author":"Yamada","year":"2013","journal-title":"Stem Cells."},{"issue":"1","key":"2024020319050762100_jbmr2464-bib-0021","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/s00784-013-0947-x","article-title":"Tissue engineering strategies for alveolar cleft reconstruction: a systematic review of the literature","volume":"18","author":"Janssen","year":"2014","journal-title":"Clin Oral Investig."},{"issue":"1","key":"2024020319050762100_jbmr2464-bib-0022","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.jcms.2011.02.003","article-title":"Repair of alveolar cleft defect with mesenchymal stem cells and platelet derived growth factors: a preliminary report","volume":"40","author":"Behnia","year":"2012","journal-title":"J Craniomaxillofac Surg."},{"issue":"3","key":"2024020319050762100_jbmr2464-bib-0023","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1111\/j.1600-0501.2010.01981.x","article-title":"Maxillary sinus floor elevation with bovine bone mineral combined with either autogenous bone or autogenous stem cells: a prospective randomized clinical trial","volume":"22","author":"Rickert","year":"2011","journal-title":"Clin Oral Implants Res."},{"issue":"2","key":"2024020319050762100_jbmr2464-bib-0024","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.tripleo.2007.12.001","article-title":"Sinus augmentation using human mesenchymal stem cells loaded into a beta-tricalcium phosphate\/hydroxyapatite scaffold","volume":"106","author":"Shayesteh","year":"2008","journal-title":"Oral Surg Oral Med Oral Pathol Oral Radiol Endod."},{"issue":"1","key":"2024020319050762100_jbmr2464-bib-0025","doi-asserted-by":"crossref","first-page":"e","DOI":"10.5037\/jomr.2014.5101","article-title":"Graft-free sinus augmentation procedure: a literature review","volume":"5","author":"Pinchasov","year":"2014","journal-title":"J Oral Maxillofac Res."},{"key":"2024020319050762100_jbmr2464-bib-0026","first-page":"C","article-title":"Interventions for replacing missing teeth: augmentation procedures of the maxillary sinus","volume":"5","author":"Esposito","year":"2014","journal-title":"Cochrane Database Syst Rev."},{"issue":"7","key":"2024020319050762100_jbmr2464-bib-0027","doi-asserted-by":"crossref","first-page":"685","DOI":"10.3727\/000000007783465172","article-title":"Good manufacturing practice-compliant expansion of marrow-derived stem and progenitor cells for cell therapy","volume":"16","author":"Gastens","year":"2007","journal-title":"Cell Transplant."},{"issue":"2","key":"2024020319050762100_jbmr2464-bib-0028","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S0011-8532(22)02107-3","article-title":"Maxillary and sinus implant reconstructions","volume":"30","author":"Tatum","year":"1986","journal-title":"Dent Clin North Am."},{"issue":"12","key":"2024020319050762100_jbmr2464-bib-0029","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1902\/jop.2005.76.12.2205","article-title":"Platelet-derived growth factor stimulates bone fill and rate of attachment level gain: results of a large multicenter randomized controlled trial","volume":"76","author":"Nevins","year":"2005","journal-title":"J Periodontol."},{"issue":"1","key":"2024020319050762100_jbmr2464-bib-0030","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.ajodo.2009.01.018","article-title":"Superimposition of 3-dimensional cone-beam computed tomography models of growing patients","volume":"136","author":"Cevidanes","year":"2009","journal-title":"Am J Orthod Dentofacial Orthop."},{"issue":"5","key":"2024020319050762100_jbmr2464-bib-0031","first-page":"457","article-title":"Analysis of tissue neogenesis in extraction sockets treated with guided bone regeneration: clinical, histologic, and micro-CT results","volume":"31","author":"Neiva","year":"2011","journal-title":"Int J Periodontics Restorative Dent."},{"key":"2024020319050762100_jbmr2464-bib-0032","article-title":"Retrospective cohort study of 4591 Straumann implants in private practice setting, with up to 10-year follow-up. Part 1: multivariate survival analysis","author":"French","year":"2014","journal-title":"Clin Oral Implants Res. Epub"},{"issue":"3 Suppl","key":"2024020319050762100_jbmr2464-bib-0033","first-page":"189","article-title":"Survival of short implants is improved with greater implant length, placement in the mandible compared with the maxilla, and in nonsmokers","volume":"12","author":"Carr","year":"2012","journal-title":"J Evid Based Dent Pract."},{"issue":"5","key":"2024020319050762100_jbmr2464-bib-0034","doi-asserted-by":"crossref","first-page":"e","DOI":"10.11607\/jomi.te13","article-title":"Bone marrow aspirate concentrate used with bovine bone mineral to reconstruct vertical and horizontal mandibular defects: report of two techniques","volume":"28","author":"Sauerbier","year":"2013","journal-title":"Int J Oral Maxillofac Implants."},{"issue":"5","key":"2024020319050762100_jbmr2464-bib-0035","doi-asserted-by":"crossref","first-page":"767","DOI":"10.3727\/096368912X652968","article-title":"Stem cell therapy for craniofacial bone regeneration: a randomized, controlled feasibility trial","volume":"22","author":"Kaigler","year":"2013","journal-title":"Cell Transplant."},{"issue":"1","key":"2024020319050762100_jbmr2464-bib-0036","first-page":"123","article-title":"Histologic and histomorphometric evaluation of an allograft stem cell-based matrix sinus augmentation procedure","volume":"26","author":"Gonshor","year":"2011","journal-title":"Int J Oral Maxillofac Implants."},{"issue":"23","key":"2024020319050762100_jbmr2464-bib-0037","doi-asserted-by":"crossref","first-page":"2227","DOI":"10.2106\/JBJS.J.01513","article-title":"Autogenous bone graft: donor sites and techniques","volume":"93","author":"Myeroff","year":"2011","journal-title":"J Bone Joint Surg Am."}],"container-title":["Journal of Bone and Mineral Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjbmr.2464","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/30\/7\/1206\/56568391\/jbmr2464.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/30\/7\/1206\/56568391\/jbmr2464.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T14:53:48Z","timestamp":1710341628000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmr\/article\/30\/7\/1206-1216\/7599267"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,2,4]]},"references-count":37,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2015,2,4]]},"published-print":{"date-parts":[[2015,7,1]]}},"URL":"https:\/\/doi.org\/10.1002\/jbmr.2464","relation":{},"ISSN":["0884-0431","1523-4681"],"issn-type":[{"value":"0884-0431","type":"print"},{"value":"1523-4681","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2015,7,1]]},"published":{"date-parts":[[2015,2,4]]}}}