Mobilization of endogenous stem cell populations enhances fracture healing in a murine femoral fracture model |
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| Authors: | Chrisoula A Toupadakis Jennifer L Granick Myrrh Sagy Alice Wong Ehssan Ghassemi Dai-Jung Chung Dori L Borjesson Clare E Yellowley |
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| Institution: | 1. Department of Anatomy, Physiology & Cell Biology, School of Veterinary Medicine, University of California Davis, Davis, California, USA;3. Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California Davis, Davis, California, USA;4. Department of Pathology, Microbiology & Immunology, School of Veterinary Medicine, University of California Davis, Davis, California, USA;2. Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St Paul, Minnesota, USA;1. Department of Veterans Affairs, San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA;2. Department of Orthopaedic Surgery, University of California, San Francisco, CA, USA;1. Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Barcelona, Av Joan XXIII s/n, 08028 Barcelona, Spain;2. Department of Chemical and Biomolecular Nanotechnology, IQAC-CSIC, Jordi Girona 18-26, 08034 Barcelona, Spain;3. Networking Research Center on Bioengineering, Biomaterials and Nanomedicine, CIBER-BBN, Barcelona, Spain;1. Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan;2. Division of Cardiovascular Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan;5. Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan;4. Department of Emergency Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan;8. Department of Medical Research, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan;3. Basic Science, Nursing Department, Meiho University, Pingtung, Taiwan;6. Department of Anatomy, Chang Gung University, Taoyuan, Taiwan;7. Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan |
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| Abstract: | Background aimsDelivery 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.MethodsA 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.ResultsAMD3100 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.ConclusionsOur 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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