In a study reported in the May 1st issue of the Journal of Clinical Investigation, Omaida Velazquez and colleagues from University of Pennsylvania Medical Center reveal why the numbers of these vital EPCs are decreased in the circulation and at wound sites in diabetes.
The authors examined diabetic mice and found that increased oxygen levels (hyperoxia) enhanced the mobilization of EPCs from the bone marrow to the peripheral blood circulation. The high oxygen levels increased the activation of the bone marrow enzyme eNOS, which stimulated nitric oxide production, helping to produce greater numbers of EPCs.
However, local injection of the chemokine stromal cell--derived factor 1 alpha (SDF-1alpha) was required to recruit these EPCs from the circulation to the wound site. The increased presence of EPCs at the wound site resulted in accelerated wound healing. The authors concluded that impaired eNOS activation and decreased SDF-1alpha expression in diabetes are responsible for the defect in diabetic wound healing.
In an accompanying commentary, Harold Brem and Marjana Tomic-Canic from Columbia University and Cornell University, respectively, reinforce that future therapeutics for diabetic wound healing will have to correct multiple deficiencies simultaneously. Therapeutic interventions, including correcting EPC activation via hyperbaric oxygen therapy and correcting EPC homing via administration of SDF-1alpha, may significantly accelerate diabetic wound healing by correcting the deficit in EPC number that is inherent to diabetic wounds.
Article: Diabetic impairments in NO-mediated endothelial progenitor cell mobilization and homing are reversed by hyperoxia and SDF-1alpha
Adapted from materials provided by Journal of Clinical Investigation.
No comments:
Post a Comment