Mobilization of endogenous stem cell populations enhances fracture healing in a murine femoral fracture model

Chrisoula A. Toupadakis, Jennifer L. Granick, Myrrh Sagy, Alice Wong, Ehssan Ghassemi, Dai Jung Chung, Dori L Borjesson, Clare E Yellowley-genetos

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Background aims: 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.

Original languageEnglish (US)
Pages (from-to)1136-1147
Number of pages12
JournalCytotherapy
Volume15
Issue number9
DOIs
StatePublished - Sep 2013

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Hematopoietic Stem Cell Mobilization
Fracture Healing
Femoral Fractures
Stem Cells
Hematopoietic Stem Cells
Population
Mesenchymal Stromal Cells
Bone Marrow
Tomography
Early Ambulation
Stress Fractures
Injections
Chemokine Receptors
Bone Fractures
Cell Transplantation
Wounds and Injuries
Bony Callus
Hematology
Inbred C57BL Mouse
Bone Density

Keywords

  • AMD3100
  • Bone regeneration
  • Fracture repair
  • Mobilization
  • Stem cells

ASJC Scopus subject areas

  • Cell Biology
  • Cancer Research
  • Transplantation
  • Genetics(clinical)
  • Oncology
  • Immunology and Allergy
  • Immunology

Cite this

Mobilization of endogenous stem cell populations enhances fracture healing in a murine femoral fracture model. / Toupadakis, Chrisoula A.; Granick, Jennifer L.; Sagy, Myrrh; Wong, Alice; Ghassemi, Ehssan; Chung, Dai Jung; Borjesson, Dori L; Yellowley-genetos, Clare E.

In: Cytotherapy, Vol. 15, No. 9, 09.2013, p. 1136-1147.

Research output: Contribution to journalArticle

Toupadakis, Chrisoula A. ; Granick, Jennifer L. ; Sagy, Myrrh ; Wong, Alice ; Ghassemi, Ehssan ; Chung, Dai Jung ; Borjesson, Dori L ; Yellowley-genetos, Clare E. / Mobilization of endogenous stem cell populations enhances fracture healing in a murine femoral fracture model. In: Cytotherapy. 2013 ; Vol. 15, No. 9. pp. 1136-1147.
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AU - Sagy, Myrrh

AU - Wong, Alice

AU - Ghassemi, Ehssan

AU - Chung, Dai Jung

AU - Borjesson, Dori L

AU - Yellowley-genetos, Clare E

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N2 - Background aims: 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.

AB - Background aims: 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.

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