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Increased Circulating Endothelial Progenitor Cells Are Associated with Survival in Acute Lung Injury

Divisions of Pulmonary, Allergy, and Critical Care, and Cardiology, Department of Medicine, Emory University School of Medicine; and the Atlanta Veterans' Affairs Medical Center, Atlanta, Georgia

Correspondence and requests for reprints should be addressed to Ellen L. Burnham, M.D., Grady Memorial Hospital, 69 Jesse Hill Jr Drive SE, Suite 2D, Atlanta, GA 30335. E-mail: eburnha{at}emory.edu

Rationale: Repair of damaged endothelium is important in recovery from acute lung injury. In animal models, bone marrow–derived endothelial progenitor cells differentiate into mature endothelium and assist in repairing damaged vasculature.

Objectives: The quantity of endothelial progenitor cells in patients with acute lung injury is unknown. We hypothesize that increased numbers of circulating endothelial progenitor cells will be associated with an improved outcome in acute lung injury and the acute respiratory distress syndrome.

Methods: Peripheral blood mononuclear cells from the buffy coat of patients with early acute lung injury (n = 45), intubated control subjects (n = 10), and healthy volunteers (n = 7) were isolated using Ficoll density gradient centrifugation, and plated on fibronectin-coated cellware. After 24 hours, nonadherent cells were removed and replated on fibronectin-coated cellware at a concentration of 1 x 10⁶ cells/well. Colony-forming units were counted after 7 days' incubation.

Measurements/Main Results: Endothelial progenitor cell colony numbers were significantly higher in patients with acute lung injury compared with healthy control subjects (p < 0.05), but did not differ between patients with acute lung injury and intubated control subjects. However, in the 45 patients with acute lung injury, improved survival correlated with a higher colony count (p < 0.04). Patients with acute lung injury with a colony count of 35 had a mortality of 30%, compared with 61% in those with colony counts < 35 (p < 0.03), results that persisted in a multivariable analysis correcting for age, sex, and severity of illness.

Conclusions: An increased number of circulating endothelial progenitor cells in acute lung injury is associated with improved survival.

Key Words: acute respiratory distress syndrome • endothelium • mortality • outcomes • stem cells

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