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Progenitor Cell Mobilization Enhances Bone Healing by Means of Improved Neovascularization and Osteogenesis

Wang, Xiao Xia M.D., D.D.S.; Allen, Robert J. Jr. M.D.; Tutela, John Paul M.D.; Sailon, Alexander M.D.; Allori, Alexander C. M.D., M.P.H.; Davidson, Edward H. M.A., M.B.B.S.; Paek, Gina K. M.D.; Saadeh, Pierre B. M.D.; McCarthy, Joseph G. M.D.; Warren, Stephen M. M.D.

Plastic and Reconstructive Surgery: August 2011 - Volume 128 - Issue 2 - p 395-405
doi: 10.1097/PRS.0b013e31821e6e10
Experimental: Original Articles

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.

New York, N.Y.; and Beijing, People's Republic of China

From the Institute of Reconstructive Plastic Surgery, New York University Langone Medical Center, and the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology.

Received for publication August 6, 2010; accepted February 8, 2011.

Presented in part at the Tissue Engineering and Regenerative Medicine International Society North America 2008 Annual Conference and Exposition, in San Diego, California, December 7 through 10, 2008, and at the 54th Annual Meeting of the Plastic Surgery Research Council, in Pittsburgh, Pennsylvania, May 27 through 30, 2009.

Disclosure: The authors received Plerixafor for experimental use through a nonfinancial relationship with Genzyme. They have no financial interests to declare.

Stephen M. Warren, M.D.; Institute of Reconstructive Plastic Surgery; New York University Medical Center; 560 First Avenue, TCH-169; New York, N.Y. 10016;

©2011American Society of Plastic Surgeons