Association of increasing burn severity in mice with delayed mobilization of circulating angiogenic cells

Objective: To perform a systematic exploration of the phenomenon of mobilization of circulating angiogenic cells (CACs) in an animal model. This phenomenon has been observed in patients with cutaneous burn wounds and may be an important mechanism for vasculogenesis in burn wound healing. Design: We used a murine model, in which burn depth can be varied precisely, and a validated culture method for quantifying circulating CACs. Setting: Michael D. Hendrix Burn Research Center, Baltimore, Maryland. Participants: Male 129S1/SvImJ mice, aged 8 weeks, and 31 patients aged 19-59 years with burn injury on 1% to 64% of the body surface area and evidence of hemodynamic stability. Main Outcome Measures: Burn wound histological features, including immunohistochemistry for blood vessels with CD31 and α-smooth muscle actin antibodies, blood flow measured with laser Doppler perfusion imaging, and mobilization of CACs into circulating blood measured with a validated culture technique. Results: Increasing burn depth resulted in a progressive delay in the time to mobilization of circulating CACs and reduced mobilization of CACs. This delay and reduction in CAC mobilization was associated with reduced perfusion and vascularization of the burn wound tissue. Analysis of CACs in the peripheral blood of the human patients, using a similar culture assay, confirmed results previously obtained by flow cytometry, that CAC levels peak early after the burn wound. Conclusion: If CAC mobilization and wound perfusion are important determinants of clinical outcome, then strategies designed to augment angiogenic responses may improve outcome in patients with severe burn wounds. Trial Registration: clinicaltrials.gov Identifier: NCT00796627