Adult stem cell mobilization enhances intramembranous bone regeneration: a pilot study

Clin Orthop Relat Res. 2012 Sep;470(9):2503-12. doi: 10.1007/s11999-012-2357-9.

Abstract

Background: Stem cell mobilization, which is defined as the forced egress of stem cells from the bone marrow to the peripheral blood (PB) using chemokine receptor agonists, is an emerging concept for enhancing tissue regeneration. However, the effect of stem cell mobilization by a single injection of the C-X-C chemokine receptor type 4 (CXCR4) antagonist AMD3100 on intramembranous bone regeneration is unclear.

Questions/purposes: We therefore asked: Does AMD3100 mobilize adult stem cells in C57BL/6 mice? Are stem cells mobilized to the PB after marrow ablation? And does AMD3100 enhance bone regeneration?

Methods: Female C57BL/6 mice underwent femoral marrow ablation surgery alone (n = 25), systemic injection of AMD3100 alone (n = 15), or surgery plus AMD3100 (n = 57). We used colony-forming unit assays, flow cytometry, and micro-CT to investigate mobilization of mesenchymal stem cells, endothelial progenitor cells, and hematopoietic stem cells to the PB and bone regeneration.

Results: AMD3100 induced mobilization of stem cells to the PB, resulting in a 40-fold increase in mesenchymal stem cells. The marrow ablation injury mobilized all three cell types to the PB over time. Administration of AMD3100 led to a 60% increase in bone regeneration at Day 21.

Conclusions: A single injection of a CXCR4 antagonist lead to stem cell mobilization and enhanced bone volume in the mouse marrow ablation model of intramembranous bone regeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / drug effects*
  • Adult Stem Cells / immunology
  • Animals
  • Benzylamines
  • Bone Marrow / drug effects
  • Bone Marrow / surgery
  • Bone Regeneration / drug effects*
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects
  • Colony-Forming Units Assay
  • Cyclams
  • Endothelial Cells / drug effects
  • Female
  • Femur / diagnostic imaging
  • Femur / drug effects*
  • Femur / immunology
  • Femur / surgery
  • Flow Cytometry
  • Hematopoietic Stem Cell Mobilization / methods*
  • Hematopoietic Stem Cells / drug effects
  • Heterocyclic Compounds / pharmacology*
  • Mesenchymal Stem Cells / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Models, Animal
  • Pilot Projects
  • Receptors, CXCR4 / antagonists & inhibitors
  • Receptors, CXCR4 / metabolism
  • Regeneration / drug effects
  • Time Factors
  • X-Ray Microtomography

Substances

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