title: Endogenous cell therapy improves bone healing.
abstract: BACKGROUND
  Although bone repair is often a relatively rapid and efficient process, many bone defects do not heal. Because an adequate blood supply is essential for new bone formation, we hypothesized that augmenting new blood vessel formation by increasing the number of circulating vasculogenic progenitor cells (PCs) with AMD3100 and enhancing their trafficking to the site of injury with recombinant human parathyroid hormone (rhPTH) will improve healing.
  
  
  METHODS
  Critical-sized 3-mm cranial defects were trephined into the right parietal bone of C57BLKS/J 6 mice (N = 120). The mice were divided into 4 equal groups (n = 30 for each). The first group received daily subcutaneous injections of AMD3100 (5 mg/kg). The second group received daily subcutaneous injections of rhPTH (5 mg/kg). The third group received both AMD3100 and rhPTH. The fourth group received subcutaneous injections of saline. Circulating vasculogenic PC numbers, new blood vessel formation, and bony regeneration were assessed. Progenitor cell adhesion, migration, and tubule formation were assessed in the presence of rhPTH and AMD3100.
  
  
  RESULTS
  Flow cytometry demonstrated that combination therapy significantly increased the number of circulating PCs compared with all other groups. In vitro, AMD3100-treated PCs had significantly increased adhesion migration, and tubule formation was assessed in the presence of rhPTH. Combination therapy significantly improved new blood vessel formation in those with cranial defect compared with all other groups. Finally, bony regeneration was significantly increased in the combination therapy group compared with all other groups.
  
  
  CONCLUSIONS
  The combination of a PC-mobilizing and traffic-enhancing agent improved bony regeneration of calvarial defects in mice.
authors.affiliation: From the *Department of Plastic Surgery, Institute of Reconstructive Plastic Surgery Laboratories, New York University Medical Center, New York, New York; and †Juntendo University School of Medicine, Department of Plastic and Reconstructive Surgery, Tokyo, Japan.
authors.forename: John
authors.initials: J
authors.lastname: Layliev
authors.forename: Alexander
authors.initials: A
authors.lastname: Marchac
authors.forename: Rica
authors.initials: R
authors.lastname: Tanaka
authors.forename: Caroline
authors.initials: C
authors.lastname: Szpalski
authors.forename: Caroline
authors.initials: C
authors.lastname: Szapalski
authors.forename: Raven
authors.initials: R
authors.lastname: Henderson
authors.forename: Marcie S
authors.initials: MS
authors.lastname: Rubin
authors.forename: Pierre B
authors.initials: PB
authors.lastname: Saadeh
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Warren
mesh_terms: D000818:Animals; D001596:Benzylamines; D001861:Bone Regeneration / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D000080027:Cyclams; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006571:Heterocyclic Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010281:Parathyroid Hormone / Q000494:pharmacology / Q000627:therapeutic use*; D010294:Parietal Bone / Q000098:blood supply / Q000293:injuries; D011994:Recombinant Proteins / Q000627:therapeutic use; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D001596:Benzylamines; D000080027:Cyclams; D006571:Heterocyclic Compounds; C470125:PTH protein, human; D010281:Parathyroid Hormone; D011994:Recombinant Proteins; C088327:plerixafor