title: Mobilization of endogenous stem cell populations enhances fracture healing in a murine femoral fracture model.
abstract: OBJECTIVE
  Delivery of bone marrow-derived stem and progenitor cells to the site of injury is an effective strategy to enhance bone healing. An alternate approach is to mobilize endogenous, heterogeneous stem cells that will home to the site of injury. AMD3100 is an antagonist of the chemokine receptor 4 (CXCR4) that rapidly mobilizes stem cell populations into peripheral blood. Our hypothesis was that increasing circulating numbers of stem and progenitor cells using AMD3100 will improve bone fracture healing.
  
  
  METHODS
  A transverse femoral fracture was induced in C57BL/6 mice, after which they were subcutaneously injected for 3 d with AMD3100 or saline control. Mesenchymal stromal cells, hematopoietic stem and progenitor cells and endothelial progenitor cells in the peripheral blood and bone marrow were evaluated by means of flow cytometry, automated hematology analysis and cell culture 24 h after injection and/or fracture. Healing was assessed up to 84 d after fracture by histomorphometry and micro-computed tomography.
  
  
  RESULTS
  AMD3100 injection resulted in higher numbers of circulating mesenchymal stromal cells, hematopoietic stem cells and endothelial progenitor cells. Micro-computed tomography data demonstrated that the fracture callus was significantly larger compared with the saline controls at day 21 and significantly smaller (remodeled) at day 84. AMD3100-treated mice have a significantly higher bone mineral density than do saline-treated counterparts at day 84.
  
  
  CONCLUSIONS
  Our data demonstrate that early cell mobilization had significant positive effects on healing throughout the regenerative process. Rapid mobilization of endogenous stem cells could provide an effective alternative strategy to cell transplantation for enhancing tissue regeneration.
authors.affiliation: Department of Anatomy, Physiology & Cell Biology, School of Veterinary Medicine, University of California Davis, Davis, CA 95616, USA.
authors.forename: Chrisoula A
authors.initials: CA
authors.lastname: Toupadakis
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Granick
authors.forename: Myrrh
authors.initials: M
authors.lastname: Sagy
authors.forename: Alice
authors.initials: A
authors.lastname: Wong
authors.forename: Ehssan
authors.initials: E
authors.lastname: Ghassemi
authors.forename: Dai-Jung
authors.initials: DJ
authors.lastname: Chung
authors.forename: Dori L
authors.initials: DL
authors.lastname: Borjesson
authors.forename: Clare E
authors.initials: CE
authors.lastname: Yellowley
mesh_terms: D000818:Animals; D001596:Benzylamines; D015519:Bone Density / Q000187:drug effects / Q000502:physiology; D001853:Bone Marrow / Q000187:drug effects / Q000502:physiology; D018929:Cell Culture Techniques / Q000379:methods*; D002478:Cells, Cultured; D000080027:Cyclams; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology; D005264:Femoral Fractures / Q000188:drug therapy / Q000503:physiopathology / Q000628:therapy*; D017102:Fracture Healing / Q000187:drug effects / Q000502:physiology*; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000502:physiology*; D006571:Heterocyclic Compounds / Q000627:therapeutic use; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology*
chemical_list: D001596:Benzylamines; D000080027:Cyclams; D006571:Heterocyclic Compounds; C088327:plerixafor
keywords: AMD3100; bone regeneration; fracture repair; mobilization; stem cells