title: Aging impairs the mobilization and homing of bone marrow-derived angiogenic cells to burn wounds.
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.
authors.affiliation: Hendrix Burn Laboratory, Department of Surgery, Johns Hopkins Bayview Medical Center, Baltimore, MD 21224, USA.
authors.forename: Xianjie
authors.initials: X
authors.lastname: Zhang
authors.forename: Kakali
authors.initials: K
authors.lastname: Sarkar
authors.forename: Sergio
authors.initials: S
authors.lastname: Rey
authors.forename: Raul
authors.initials: R
authors.lastname: Sebastian
authors.forename: Efstathia
authors.initials: E
authors.lastname: Andrikopoulou
authors.forename: Guy P
authors.initials: GP
authors.lastname: Marti
authors.forename: Karen
authors.initials: K
authors.lastname: Fox-Talbot
authors.forename: Gregg L
authors.initials: GL
authors.lastname: Semenza
authors.forename: John W
authors.initials: JW
authors.lastname: Harmon
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002056:Burns / Q000097:blood* / Q000473:pathology*; D002452:Cell Count; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D018919:Neovascularization, Physiologic / Q000235:genetics; D010477:Perfusion; D014945:Wound Healing
chemical_list: D054377:Chemokine CXCL12; D051795:Hypoxia-Inducible Factor 1, alpha Subunit