{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:29:44Z","timestamp":1791296984822,"version":"4.1.0"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2007,8,1]],"date-time":"2007-08-01T00:00:00Z","timestamp":1185926400000},"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":[[2007,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Stem cell and tissue engineering\u2014based therapies have become a promising option to heal bony defects in the future. Human cord blood\u2014derived mesenchymal stem cells were seeded onto a collagen\/tricalcium phosphate scaffold and xenotransplanted into critical size femoral defects of 46 nude rats. We found a survival of human cells within the scaffold and surrounding bone\/bone marrow up to 4 wk after transplantation and an increased bone healing rate compared with controls without stem cells. This study supports the application of cord blood stem cells for bone regeneration.<\/jats:p>\n                  <jats:p>Introduction: The treatment of critical size bone defects is still a challenging problem in orthopedics. In this study, the survival, migration, and bone healing promoting potency of cord blood\u2014derived stem cells were elucidated after xenotransplantation into a critical size femoral defect in athymic nude rats.<\/jats:p>\n                  <jats:p>Materials and Methods: Unrestricted somatic stem cells (USSCs) isolated from human cord blood were tested toward their mesenchymal in vitro potency and cultivated onto a collagen I\/III and \u03b2-tricalcium phosphate (\u03b2-TCP) scaffold. The biomaterial-USSC composite was transplanted into a 4-mm femoral defect of 40 nude rats and stabilized by an external fixator. Twelve animals without USSCs served as controls. Cell survival, migration, and bone formation were evaluated by blood samples, X-rays, and histological and immunocytochemical analysis of different organs within a maximal postoperative follow-up of 10 wk.<\/jats:p>\n                  <jats:p>Results: Of the 52 nude rats, 46 animals were evaluated (drop-out rate: 11.5%). Human-derived stem cells showed an engraftment within the scaffold and adjacent femur up to 4 wk after xenotransplantation. With further time, the human cells were destroyed by the host organism. We found a significant increase in bone formation in the study group compared with controls. USSC transplantation did not significantly influence blood count or body weight in athymic nude rats. Whereas the collagen I\/III scaffold was almost resorbed 10 wk after transplantation, there were still significant amounts of TCP present in transplantation sites at this time.<\/jats:p>\n                  <jats:p>Conclusions: Human cord blood\u2014derived stem cells showed significant engraftment in bone marrow, survived within a collagen-TCP scaffold up to 4 wk, and increased local bone formation in a nude rat's femoral defect.<\/jats:p>","DOI":"10.1359\/jbmr.070414","type":"journal-article","created":{"date-parts":[[2007,4,23]],"date-time":"2007-04-23T14:52:48Z","timestamp":1177339968000},"page":"1224-1233","source":"Crossref","is-referenced-by-count":79,"title":["Bone Healing and Migration of Cord Blood\u2014Derived Stem Cells Into a Critical Size Femoral Defect After Xenotransplantation"],"prefix":"10.1093","volume":"22","author":[{"given":"Marcus","family":"J\u00e4ger","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA"},{"name":"Research Laboratory for Regenerative Medicine and Biomaterials, Department of Orthopaedics, Heinrich-Heine University Medical School, Duesseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d6zer","family":"Degistirici","sequence":"additional","affiliation":[{"name":"Kourion Therapeutics AG, Langenfeld, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Knipper","sequence":"additional","affiliation":[{"name":"Kourion Therapeutics AG, Langenfeld, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Fischer","sequence":"additional","affiliation":[{"name":"Institute of Transplantation Diagnostic and Cell Therapy, Heinrich-Heine-University, Duesseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Sager","sequence":"additional","affiliation":[{"name":"Animal Research Laboratory, Heinrich-Heine-University, Duesseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u00fcdiger","family":"Krauspe","sequence":"additional","affiliation":[{"name":"Research Laboratory for Regenerative Medicine and Biomaterials, Department of Orthopaedics, Heinrich-Heine University Medical School, Duesseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,12,4]]},"reference":[{"key":"2024020319283764800_bib1","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.humimm.2006.03.015","article-title":"Why cord blood?","volume":"67","author":"Rubinstein","year":"2006","journal-title":"Hum Immunol"},{"key":"2024020319283764800_bib2","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1046\/j.1365-2141.2000.01986.x","article-title":"Mesenchymal progenitor cells in human umbilical cord blood","volume":"109","author":"Erices","year":"2000","journal-title":"Br J Haematol"},{"key":"2024020319283764800_bib3","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1084\/jem.20040440","article-title":"A new human somatic stem cell from placental cord blood with intrinsic pluripotent differentiation potential","volume":"200","author":"K\u00f6gler","year":"2004","journal-title":"J Exp Med"},{"key":"2024020319283764800_bib4","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1111\/j.1445-5994.2006.01079.x","article-title":"Unrelated umbilical cord blood transplantation for adults with haematological malignancies: Results from a single Australian centre","volume":"36","author":"Bradstock","year":"2006","journal-title":"Intern Med J"},{"key":"2024020319283764800_bib5","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1097\/01.tp.0000188172.26531.6f","article-title":"Recipient-specific tolerance after HLA-mismatched umbilical cord blood stem cell transplantation","volume":"80","author":"Kleen","year":"2005","journal-title":"Transplantation"},{"key":"2024020319283764800_bib6","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.cellbi.2005.12.009","article-title":"Characterization of two populations of mesenchymal progenitor cells in umbilical cord blood","volume":"30","author":"Chang","year":"2006","journal-title":"Cell Biol Int"},{"key":"2024020319283764800_bib7","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1007\/s00277-004-0918-z","article-title":"Mesenchymal progenitor cells in the human umbilical cord","volume":"83","author":"Kim","year":"2004","journal-title":"Ann Hematol"},{"key":"2024020319283764800_bib8","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1182\/blood-2003-05-1670","article-title":"Isolation of multipotent mesenchymal stem cells from umbilical cord blood","volume":"103","author":"Lee","year":"2004","journal-title":"Blood"},{"key":"2024020319283764800_bib9","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1007\/s00277-005-0047-3","article-title":"Mesenchymal stem cells feeder layer from human umbilical cord blood for ex vivo expanded growth and proliferation of hematopoietic progenitor cells","volume":"85","author":"Jang","year":"2006","journal-title":"Ann Hematol"},{"key":"2024020319283764800_bib10","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1515\/bmte.2003.48.9.241","article-title":"Influence of different culture solutions on osteoblastic differentiation in cord blood and bone marrow derived progenitor cells","volume":"48","author":"J\u00e4ger","year":"2003","journal-title":"Biomed Tech (Berl)"},{"key":"2024020319283764800_bib11","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.exphem.2005.01.012","article-title":"Cytokine production and hematopoiesis supporting activity of cord blood-derived unrestricted somatic stem cells","volume":"33","author":"K\u00f6gler","year":"2005","journal-title":"Exp Hematol"},{"key":"2024020319283764800_bib12","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1016\/j.exphem.2006.07.011","article-title":"Comparative generation and characterization of pluripotent unrestricted somatic stem cells with mesenchymal stem cells from human cord blood","volume":"34","author":"K\u00f6gler","year":"2006","journal-title":"Exp Hematol"},{"key":"2024020319283764800_bib13","first-page":"205","article-title":"Ovine cord blood accommodates multipotent mesenchymal progenitor cells","volume":"20","author":"J\u00e4ger","year":"2006","journal-title":"In Vivo"},{"key":"2024020319283764800_bib14","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1007\/s10439-005-5889-2","article-title":"Proliferation and osteogenic differentiation of mesenchymal stem cells cultured onto three different polymers in vitro","volume":"33","author":"J\u00e4ger","year":"2005","journal-title":"Ann Biomed Eng"},{"key":"2024020319283764800_bib15","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1002\/jbm.a.30515","article-title":"Extensive H(+) release by bone substitutes affects biocompatibility in vitro testing","volume":"76","author":"J\u00e4ger","year":"2006","journal-title":"J Biomed Mater Res A"},{"key":"2024020319283764800_bib16","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1515\/BMT.2005.020","article-title":"The critical size bony defect in a small animal for bone healing studies (II): Implant evolution and surgical technique on a rat's femur","volume":"50","author":"J\u00e4ger","year":"2005","journal-title":"Biomed Tech (Berl)"},{"key":"2024020319283764800_bib17","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1515\/BMT.2005.015","article-title":"The critical size bony defect in a small animal for bone healing studies (I): Comparative anatomical study on rats' femur","volume":"50","author":"J\u00e4ger","year":"2005","journal-title":"Biomed Tech (Berl)"},{"key":"2024020319283764800_bib18","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1089\/scd.2004.13.325","article-title":"Culture and characterization of human embryonic stem cells","volume":"13","author":"Draper","year":"2004","journal-title":"Stem Cells Dev"},{"key":"2024020319283764800_bib19","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1046\/j.1469-7580.2002.00030.x","article-title":"Surface antigens of human embryonic stem cells: Changes upon differentiation in culture","volume":"200","author":"Draper","year":"2002","journal-title":"J Anat"},{"key":"2024020319283764800_bib20","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.ajog.2003.07.022","article-title":"Immunologic properties of human fetal mesenchymal stem cells","volume":"190","author":"Gotherstrom","year":"2004","journal-title":"Am J Obstet Gynecol"},{"key":"2024020319283764800_bib21","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1634\/stemcells.22-5-675","article-title":"Study of telomere length reveals rapid aging of human marrow stromal cells following in vitro expansion","volume":"22","author":"Baxter","year":"2004","journal-title":"Stem Cells"},{"key":"2024020319283764800_bib22","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1016\/S0301-472X(03)00110-3","article-title":"HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells","volume":"31","author":"Le Blanc","year":"2003","journal-title":"Exp Hematol"},{"key":"2024020319283764800_bib23","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1089\/scd.2005.14.252","article-title":"Immunogenicity of adult mesenchymal stem cells: Lessons from the fetal allograft","volume":"14","author":"Barry","year":"2005","journal-title":"Stem Cells Dev"},{"key":"2024020319283764800_bib24","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1634\/stemcells.2005-0008","article-title":"Role for interferon-gamma in the immunomodulatory activity of human bone marrow mesenchymal stem cells","volume":"24","author":"Krampera","year":"2006","journal-title":"Stem Cells"},{"key":"2024020319283764800_bib25","doi-asserted-by":"crossref","first-page":"4619","DOI":"10.1182\/blood-2003-11-3909","article-title":"Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3-dioxygenase-mediated tryptophan degradation","volume":"103","author":"Meisel","year":"2004","journal-title":"Blood"},{"key":"2024020319283764800_bib26","doi-asserted-by":"crossref","first-page":"555","DOI":"10.3727\/000000003108747154","article-title":"Human cord blood-derived mesenchymal stem cells home and survive in the marrow of immunodeficient mice after systemic infusion","volume":"12","author":"Erices","year":"2003","journal-title":"Cell Transplant"},{"key":"2024020319283764800_bib27","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1016\/S0301-472X(02)00820-2","article-title":"Mesenchymal stem cells promote engraftment of human umbilical cord blood-derived CD34(+) cells in NOD\/SCID mice","volume":"30","author":"Noort","year":"2002","journal-title":"Exp Hematol"},{"key":"2024020319283764800_bib28","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/j.1749-6632.2001.tb03569.x","article-title":"Ex vivo expansion and engraftment potential of cord blood-derived CD34+ cells in NOD\/SCID mice","volume":"938","author":"Fibbe","year":"2001","journal-title":"Ann N Y Acad Sci"},{"key":"2024020319283764800_bib29","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1634\/stemcells.2005-0224","article-title":"In vitro characteristics and in vivo immunosuppressive activity of compact bone-derived murine mesenchymal progenitor cells","volume":"24","author":"Guo","year":"2006","journal-title":"Stem Cells"},{"key":"2024020319283764800_bib30","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1038\/sj.bmt.1704400","article-title":"Human mesenchymal stem cells support unrelated donor hematopoietic stem cells and suppress T-cell activation","volume":"33","author":"Maitra","year":"2004","journal-title":"Bone Marrow Transplant"},{"key":"2024020319283764800_bib31","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/S0301-472X(03)00202-9","article-title":"Nonexpanded primary lung and bone marrow-derived mesenchymal cells promote the engraftment of umbilical cord blood-derived CD34(+) cells in NOD\/SCID mice","volume":"31","author":"in't Anker","year":"2003","journal-title":"Exp Hematol"},{"key":"2024020319283764800_bib32","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1016\/j.jtcvs.2003.07.037","article-title":"Xenoreactivity and engraftment of human mesenchymal stem cells transplanted into infarcted rat myocardium","volume":"127","author":"Grinnemo","year":"2004","journal-title":"J Thorac Cardiovasc Surg"},{"key":"2024020319283764800_bib33","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1182\/blood-2005-02-0572","article-title":"Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion","volume":"106","author":"Sato","year":"2005","journal-title":"Blood"},{"key":"2024020319283764800_bib34","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.surg.2006.04.003","article-title":"Mesenchymal stem cells enhance xenochimerism in NK-depleted hosts","volume":"140","author":"Moadsiri","year":"2006","journal-title":"Surgery"},{"key":"2024020319283764800_bib35","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1002\/jor.20047","article-title":"In utero transplantation of human bone marrow-derived multipotent mesenchymal stem cells in mice","volume":"24","author":"Chou","year":"2006","journal-title":"J Orthop Res"},{"key":"2024020319283764800_bib36","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1080\/146532401753277571","article-title":"Multilineage differentiation of human MSC after in utero transplantation","volume":"3","author":"Mackenzie","year":"2001","journal-title":"Cytotherapy"},{"key":"2024020319283764800_bib37","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1038\/81395","article-title":"Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep","volume":"6","author":"Liechty","year":"2000","journal-title":"Nat Med"},{"key":"2024020319283764800_bib38","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1369\/jhc.4A6280.2005","article-title":"Behavior of transplanted bone marrow-derived GFP mesenchymal cells in osteochondral defect as a simulation of autologous transplantation","volume":"53","author":"Oshima","year":"2005","journal-title":"J Histochem Cytochem"},{"key":"2024020319283764800_bib39","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1634\/stemcells.2005-0430","article-title":"Progenitors systemically transplanted into neonatal mice localize to areas of active bone formation in vivo: Implications of cell therapy for skeletal diseases","volume":"24","author":"Wang","year":"2006","journal-title":"Stem Cells"},{"issue":"Suppl","key":"2024020319283764800_bib40","doi-asserted-by":"crossref","first-page":"S62","DOI":"10.1097\/01.blo.0000143819.82510.0d","article-title":"Osteochondral defect repair by demineralized cortical bone matrix","volume":"427","author":"Gao","year":"2004","journal-title":"Clin Orthop"},{"key":"2024020319283764800_bib41","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1089\/ten.2006.12.1753","article-title":"Efficacy of bone marrow-derived stem cells in strengthening osteoporotic bone in a rabbit model","volume":"12","author":"Wang","year":"2006","journal-title":"Tissue Eng"},{"key":"2024020319283764800_bib42","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/S0070-2153(05)67010-X","article-title":"Skeletal stem cells in regenerative medicine","volume":"67","author":"Sonoyama","year":"2005","journal-title":"Curr Top Dev Biol"},{"key":"2024020319283764800_bib43","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1002\/0470867973.ch9","article-title":"Mesenchymal stem cells and bioceramics: Strategies to regenerate the skeleton","volume":"249","author":"Ohgushi","year":"2003","journal-title":"Novartis Found Symp"},{"key":"2024020319283764800_bib44","doi-asserted-by":"crossref","first-page":"2203","DOI":"10.1089\/ten.2006.12.2203","article-title":"Species specificity of ectopic bone formation using periosteum-derived mesenchymal progenitor cells","volume":"12","author":"Eyckmans","year":"2006","journal-title":"Tissue Eng"},{"key":"2024020319283764800_bib45","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1089\/ten.2005.11.120","article-title":"Healing of critically sized femoral defects, using genetically modified mesenchymal stem cells from human adipose tissue","volume":"11","author":"Peterson","year":"2005","journal-title":"Tissue Eng"},{"key":"2024020319283764800_bib46","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1089\/ten.2005.11.1407","article-title":"Rapid isolation, expansion, and differentiation of osteoprogenitors from full-term umbilical cord blood","volume":"11","author":"Hutson","year":"2005","journal-title":"Tissue Eng"},{"key":"2024020319283764800_bib47","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1111\/j.1067-1927.2004.012118.x","article-title":"Cranial bone defect healing is accelerated by mesenchymal stem cells induced by coadministration of bone morphogenetic protein-2 and basic fibroblast growth factor","volume":"12","author":"Akita","year":"2004","journal-title":"Wound Repair Regen"},{"key":"2024020319283764800_bib48","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1089\/107632703764664819","article-title":"Human mesenchymal stem cells transduced with recombinant bone morphogenetic protein-9 adenovirus promote osteogenesis in rodents","volume":"9","author":"Dayoub","year":"2003","journal-title":"Tissue Eng"},{"key":"2024020319283764800_bib49","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1002\/jbm.a.30208","article-title":"Accelerated bone repair with the use of a synthetic BMP-2-derived peptide and bone-marrow stromal cells","volume":"72","author":"Saito","year":"2005","journal-title":"J Biomed Mater Res A"},{"key":"2024020319283764800_bib50","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/S0736-0266(02)00108-0","article-title":"Engineered allogeneic mesenchymal stem cells repair femoral segmental defect in rats","volume":"21","author":"Tsuchida","year":"2003","journal-title":"J Orthop Res"},{"key":"2024020319283764800_bib51","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1097\/00006123-200211000-00020","article-title":"Ex vivo bone morphogenetic protein-9 gene therapy using human mesenchymal stem cells induces spinal fusion in rodents","volume":"51","author":"Dumont","year":"2002","journal-title":"Neurosurgery"},{"key":"2024020319283764800_bib52","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1006\/bbrc.2002.6623","article-title":"Adenoviral BMP-2 gene transfer in mesenchymal stem cells: In vitro and in vivo bone formation on biodegradable polymer scaffolds","volume":"292","author":"Partridge","year":"2002","journal-title":"Biochem Biophys Res Commun"}],"container-title":["Journal of Bone and Mineral Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1359%2Fjbmr.070414","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/22\/8\/1224\/56574924\/5650220810.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/22\/8\/1224\/56574924\/5650220810.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T10:49:00Z","timestamp":1710326940000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmr\/article\/22\/8\/1224-1233\/7597421"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,8,1]]},"references-count":52,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2009,12,4]]},"published-print":{"date-parts":[[2007,8,1]]}},"URL":"https:\/\/doi.org\/10.1359\/jbmr.070414","relation":{},"ISSN":["0884-0431","1523-4681"],"issn-type":[{"value":"0884-0431","type":"print"},{"value":"1523-4681","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2007,8,1]]},"published":{"date-parts":[[2007,8,1]]}}}