title: Human blood-derived endothelial progenitor cells augment vasculogenesis and osteogenesis.
abstract: BACKGROUND
  Endothelial progenitor cells (EPC) participate in angiogenesis and osteogenesis, therefore, have the potential to enhance extra-cortical bone formation.
  
  
  OBJECTIVE
  To enhance extra-cortical bone formation following local transplantation of human peripheral blood-derived EPC (hEPC) in a guided bone regeneration (GBR) nude rat calvaria model.
  
  
  METHODS
  hEPC were isolated from peripheral blood of healthy volunteers. Cells were cultured and characterized by flow cytometry for specific endothelial markers. Following exposure of nude rat calvaria, gold domes were filled with 10(6) hEPC mixed with βTCP (n = 6). Domes filled with βTCP served as control (n = 6). Rats were sacrificed after 3 months. New bone formation and blood vessel density were analysed by histology and histomorphometry. Transplanted hEPC were located in the regenerated tissue using immunohistology.
  
  
  RESULTS
  Abundant vasculature was observed adjacent to the newly formed bone. According to histomorphometric analysis: blood vessel density was 7.5 folds higher in the hEPC compared with the control group. Similarly, gained extra-cortical bone height (2.46 ± 1.1 mm versus 0.843 ± 0.61 mm, p = 0.01) and bone area fraction (19.42 ± 7.48% versus 4.81 ± 3.93%, p = 0.001) were elevated following hEPC transplantation. Moreover, hEPC expressing human-specific CD31 were integrated into blood vessel walls adjacent to newly formed bone.
  
  
  CONCLUSIONS
  In nude rat GBR calvaria model, transplantation of hEPC significantly enhanced vasculogenesis and osteogenesis.
authors.affiliation: Department of Periodontology, School of Graduate Dentistry, Haifa, Israel; Research Institute for Bone Repair, Rambam Health Care Campus, Haifa, Israel; The Rappaport Family Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.
authors.forename: Hadar
authors.initials: H
authors.lastname: Zigdon-Giladi
authors.forename: Gal
authors.initials: G
authors.lastname: Michaeli-Geller
authors.forename: Tova
authors.initials: T
authors.lastname: Bick
authors.forename: Dina
authors.initials: D
authors.lastname: Lewinson
authors.forename: Eli E
authors.initials: EE
authors.lastname: Machtei
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D001769:Blood; D001808:Blood Vessels / Q000254:growth & development; D001861:Bone Regeneration / Q000502:physiology; D002130:Calcium Phosphates / Q000737:chemistry; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible / Q000737:chemistry; D042783:Endothelial Cells / Q000502:physiology*; D005353:Fibronectins / Q000737:chemistry; D048091:Guided Tissue Regeneration / Q000379:methods; D064593:Heterografts / Q000637:transplantation; D006801:Humans; D008297:Male; D018919:Neovascularization, Physiologic / Q000502:physiology*; D010012:Osteogenesis / Q000502:physiology*; D010294:Parietal Bone / Q000601:surgery; D051381:Rats; D011923:Rats, Nude; D033581:Stem Cell Transplantation / Q000379:methods; D013234:Stem Cells / Q000502:physiology*; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D001672:Biocompatible Materials; D002130:Calcium Phosphates; D020099:Coated Materials, Biocompatible; D005353:Fibronectins; C485817:beta-tricalcium phosphate
keywords: cell therapy; endothelial progenitor cells; extra-cortical bone augmentation; guided bone regeneration; tissue engineering