Aging impairs the mobilization and homing of bone marrow-derived angiogenic cells to burn wounds |
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| Authors: | Zhang Xianjie Sarkar Kakali Rey Sergio Sebastian Raul Andrikopoulou Efstathia Marti Guy P Fox-Talbot Karen Semenza Gregg L Harmon John W |
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| Affiliation: | (1) Hendrix Burn Laboratory, Department of Surgery, Johns Hopkins Bayview Medical Center, Baltimore, MD 21224, USA;(2) Vascular Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA;(3) Department of Pediatrics, Oncology, Radiation Oncology, and Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA;(4) Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA;(5) McKusick-Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA;(6) Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA;(7) Present address: Section of Surgical Sciences, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; |
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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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