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Back to 2011 Posters
Progenitor Cell Mobilization Improves Bony Healing
John Layliev, Alexander Marchac, MD, Parag Butala, MD, Raven Henderson, MD, Caroline Szpalski, MD, Fabio Sagebin, BS, Andrew Weinstein, BS, Pierre B. Saadeh, MD, FACS, Stephen M. Warren, MD, FACS.
NYU Langone Medical Center, New York, NY, USA.
BACKGROUND:
Despite bone repair being a relatively rapid and efficient process, many patients fail to heal their fractures. Since an adequate blood supply is essential for osteogenesis, we hypothesize that augmenting neovascularization will improve bony healing, especially when administered in conjunction with a chemotaxis enhancing drug.
METHODS:
A circular critical size 3-mm cranial defect was made in the right parietal bones of 6 week old FVB mice. Mice were separated into four groups. One group (n=30) received daily subcutaneous AMD3100 (10mg/kg) injection beginning on postoperative day 3 and continuing for 14 days. The second group (n=30) received daily injection of a chemoattractant. The third group (n=30) received administration of both drugs. The fourth group (n=30) received subcutaneous saline injection. Skulls were harvested at 12 weeks. Flow cytometry was used to quantify the amount of progenitor cells in peripheral blood obtained via intracardiac puncture. Immunofluorescent CD31 and osteocalcin staining of skull specimens was performed to assess for vascularity and osteoblast activity. Microcomputed tomography was used to assess bony regeneration.
RESULTS:
Flow cytometry demonstrated increased progenitor cell levels in the AMD3100 group (8.03±1.50% vs. 3.23±1.33% at day 14, p<0.05), and increased progenitor cell levels in the AMD3100 and chemoattractant combination treatment arm (11.44±1.21% vs. 3.23±1.33% at day 14). Calvarial defects of AMD3100-treated mice harvested at 4 weeks demonstrated increased vascularity (3.07±0.91% vs. 5.44±1.89%, p<0.01) and osteoblast density (1.96±0.54% vs. 3.36±0.52%, p<0.01) compared to controls. AMD3100-treatment significantly improved bony regeneration on microcomputed tomography at 12 weeks (36.01±5.66% vs. 61.85±11.45%, p<0.001) compared to controls. The AMD3100 combined with chemoattractant treatment arm yielded the most dramatic bony regeneration (90.6±3.82% vs. 36.01±5.66%, P<.001) compared to controls.
CONCLUSIONS:
Mobilizing progenitor cells and improving their trafficking to an ischemic site increases the amount of endothelial progenitor cells at a fracture site which then leads to increased vascularity. A dense vascular bed leads to increased bone density. Collectively, progenitor cell trafficking enhances osteogenesis.
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