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Aging impairs the mobilization and homing of bone marrow-derived angiogenic cells to burn wounds

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Abstract

Impaired wound healing in the elderly represents a major clinical problem. Delineating the cellular and molecular mechanisms by which aging impairs wound healing may lead to the development of improved treatment strategies for elderly patients with non-healing wounds. Neovascularization is an essential step in wound healing, and bone marrow-derived angiogenic cells (BMDACs) play an important role in vascularization. Using a mouse full-thickness burn wound model, we demonstrate that perfusion and vascularization of burn wounds were impaired by aging and were associated with dramatically reduced mobilization of BMDACs bearing the cell surface molecules CXCR4 and Sca1. Expression of stromal-derived factor 1 (SDF-1), the cytokine ligand for CXCR4, was significantly decreased in peripheral blood and burn wounds of old mice. Expression of hypoxia-inducible factor (HIF)-1α was detected in burn wounds from young (2-month-old), but not old (2-year-old), mice. When BMDACs from young donor mice were injected intravenously, homing to burn wound tissue was impaired in old recipient mice, whereas the age of the BMDAC donor mice had no effect on homing. Our results indicate that aging impairs burn wound vascularization by impairing the mobilization of BMDACs and their homing to burn wound tissue as a result of impaired HIF-1 induction and SDF-1 signaling.

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Acknowledgments

This work was supported by NIH grant P20-GM078494, the Johns Hopkins Institute for Cell Engineering, and the Hendrix Burn Fund of Johns Hopkins University. We thank Karen Padgett of Novus Biologicals Inc. for generously providing anti-HIF-1 antibody.

Disclosure statement

G.L.S. is the C. Michael Armstrong Professor at the Johns Hopkins University School of Medicine. All authors confirm that there is no conflict of interest associated with this publication.

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Author notes

  1. Xianjie Zhang

    Present address: Section of Surgical Sciences, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

Authors and Affiliations

  1. Hendrix Burn Laboratory, Department of Surgery, Johns Hopkins Bayview Medical Center, Baltimore, MD, 21224, USA

    Xianjie Zhang, Raul Sebastian, Efstathia Andrikopoulou, Guy P. Marti & John W. Harmon

  2. Vascular Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA

    Kakali Sarkar, Sergio Rey & Gregg L. Semenza

  3. Department of Pediatrics, Oncology, Radiation Oncology, and Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA

    Gregg L. Semenza

  4. Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA

    Kakali Sarkar & Gregg L. Semenza

  5. McKusick-Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA

    Sergio Rey & Gregg L. Semenza

  6. Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA

    Karen Fox-Talbot

Authors
  1. Xianjie Zhang
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Correspondence to Gregg L. Semenza or John W. Harmon.

Additional information

X. Zhang and K. Sarkar contributed equally to this work.

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Zhang, X., Sarkar, K., Rey, S. et al. Aging impairs the mobilization and homing of bone marrow-derived angiogenic cells to burn wounds. J Mol Med 89, 985–995 (2011). https://doi.org/10.1007/s00109-011-0754-2

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  • DOI: https://doi.org/10.1007/s00109-011-0754-2

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