title: Progenitor cell mobilization enhances bone healing by means of improved neovascularization and osteogenesis.
abstract: BACKGROUND
  Although bone repair is a relatively efficient process, a significant portion of patients fail to heal their fractures. Because adequate blood supply is essential to osteogenesis, the authors hypothesize that augmenting neovascularization by increasing the number of circulating progenitor cells will improve bony healing.
  
  
  METHODS
  Bilateral full-thickness defects were created in the parietal bones of C57 wild-type mice. Intraperitoneal AMD3100 (n = 33) or sterile saline (n = 33) was administered daily beginning on postoperative day 3 and continuing through day 18. Circulating progenitor cell number was quantified by fluorescence-activated cell sorting. Bone regeneration was assessed with micro-computed tomography. Immunofluorescent CD31 and osteocalcin staining was performed to assess for vascularity and osteoblast density.
  
  
  RESULTS
  AMD3100 treatment increased circulating progenitor cell levels and significantly improved bone regeneration. Calvarial defects of AMD3100-treated mice demonstrated increased vascularity and osteoblast density.
  
  
  CONCLUSIONS
  Improved bone regeneration in this model was associated with elevated circulating progenitor cell number and subsequently improved neovascularization and osteogenesis. These findings highlight the importance of circulating progenitor cells in bone healing and may provide a novel therapy for bone regeneration.
authors.affiliation: New York, N.Y.; and Beijing, People's Republic of China From the Institute of Reconstructive Plastic Surgery, New York University Langone Medical Center, and the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology.
authors.forename: Xiao Xia
authors.initials: XX
authors.lastname: Wang
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Allen
authors.forename: John Paul
authors.initials: JP
authors.lastname: Tutela
authors.forename: Alexander
authors.initials: A
authors.lastname: Sailon
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Allori
authors.forename: Edward H
authors.initials: EH
authors.lastname: Davidson
authors.forename: Gina K
authors.initials: GK
authors.lastname: Paek
authors.forename: Pierre B
authors.initials: PB
authors.lastname: Saadeh
authors.forename: Joseph G
authors.initials: JG
authors.lastname: McCarthy
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Warren
mesh_terms: D000818:Animals; D001596:Benzylamines; D001861:Bone Regeneration / Q000187:drug effects / Q000502:physiology*; D016723:Bone Remodeling / Q000187:drug effects / Q000502:physiology; D002452:Cell Count; D000080027:Cyclams; D004195:Disease Models, Animal; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006571:Heterocyclic Compounds / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D010006:Osteoblasts / Q000187:drug effects / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*; D010294:Parietal Bone / Q000098:blood supply / Q000293:injuries / Q000473:pathology; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D055114:X-Ray Microtomography
chemical_list: D001596:Benzylamines; D000080027:Cyclams; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; C088327:plerixafor