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

Xianjie Zhang, Kakali Sarkar, Sergio Rey, Raul Sebastian, Efstathia Andrikopoulou, Guy P. Marti, Karen Fox-Talbot, Gregg L. Semenza, John W. Harmon

Research output: Contribution to journalArticle

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 fullthickness 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)-1a 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.

Original languageEnglish (US)
Pages (from-to)985-995
Number of pages11
JournalJournal of Molecular Medicine
Volume89
Issue number10
DOIs
StatePublished - Oct 1 2011

Keywords

  • Aging
  • Bone marrow-derived angiogenic cells
  • Burn wound healing
  • Hypoxia-inducible factor 1
  • Neovascularization
  • Stromal-derived factor 1

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Genetics(clinical)

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