Progenitor cell mobilization enhances bone healing by means of improved neovascularization and osteogenesis

Plast Reconstr Surg. 2011 Aug;128(2):395-405. doi: 10.1097/PRS.0b013e31821e6e10.

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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Benzylamines
  • Bone Regeneration / drug effects
  • Bone Regeneration / physiology*
  • Bone Remodeling / drug effects
  • Bone Remodeling / physiology
  • Cell Count
  • Cyclams
  • Disease Models, Animal
  • Hematopoietic Stem Cell Mobilization / methods*
  • Heterocyclic Compounds / pharmacokinetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neovascularization, Physiologic / drug effects
  • Neovascularization, Physiologic / physiology*
  • Osteoblasts / drug effects
  • Osteoblasts / pathology
  • Osteogenesis / drug effects
  • Osteogenesis / physiology*
  • Parietal Bone / blood supply
  • Parietal Bone / injuries
  • Parietal Bone / pathology
  • Receptors, CXCR4 / antagonists & inhibitors
  • Stem Cells / cytology
  • Stem Cells / drug effects
  • Stem Cells / physiology*
  • X-Ray Microtomography

Substances

  • Benzylamines
  • Cyclams
  • Heterocyclic Compounds
  • Receptors, CXCR4
  • plerixafor