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Xianjie Zhang, MD, PhD; Xiaofei Wei, MD; Lixin Liu, PhD; Guy P. Marti, MD; Mohammed S. Ghanamah, MD; Muhammad J. Arshad, MD; Lori Strom, BS; Robert Spence, MD; James Jeng, MD; Stephen Milner, MD; John W. Harmon, MD; Gregg L. Semenza, MD, PhD

Arch Surg. 2010;145(3):259-266.

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 -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

Author Affiliations: Section of Surgical Sciences, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China (Dr Zhang); Section of Surgical Sciences and the Michael D. Hendrix Burn Research Center (Drs Zhang, Liu, Marti, Ghanamah, Arshad, Spence, Milner, and Harmon and Ms Strom), Vascular Program, Institute for Cell Engineering, Departments of Pediatrics, Medicine, Oncology, and Radiation Oncology, and McKusick-Nathans Institute of Genetic Medicine (Drs Wei and Semenza), The Johns Hopkins University School of Medicine, Baltimore, Maryland; and Burn Center, Washington Hospital Center, Washington DC (Dr Jeng).

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