Published ahead of print on June 23, 2005, doi:10.1164/rccm.200410-1325OC
Am. J. Respir. Crit. Care Med., Volume 172, Number 7, October 2005, 854-860
A more recent version of this article appeared on October 1, 2005
Submitted on October 6, 2004
Accepted on June 22, 2005
Increased Circulating Endothelial Progenitor Cells are Associated with Survival in Acute Lung Injury
Ellen L Burnham1*, W. Robert Taylor2, Arshed A Quyyumi1, Mauricio Rojas1, Kenneth L Brigham1, and Marc Moss1
1 Department of Medicine, Division of Pulmonary, Allergy and Critical Care and the Division of Cardiology, Emory University School of Medicine, Atlanta, GA, USA,
2 Atlanta Veterans' Affairs Medical Center, Atlanta, GA, USA
* To whom correspondence should be addressed. 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 controls (n=10), and healthy volunteers (n=7) were isolated using Ficoll density gradient centrifugation, and plated on fibronectin-coated cellware. After 24 hours, non-adherent cells were removed and re-plated on fibronectin-coated cellware at a concentration of 1x106 cells/well. Colony-forming units were counted after 7 days' incubation.
Measurements/ main results: Endothelial progenitor cell colony numbers were significantly higher in acute lung injury patients compared to healthy controls (p<0.05), but did not differ between acute lung injury patients and intubated controls. However, in the 45 acute lung injury patients, improved survival correlated with a higher colony count (p<0.04). Acute lung injury patients with a colony count of 35 had a mortality of 30%, compared to 61% in those with colony counts <35 (p<0.03), results that persisted in a multivariable analysis correcting for age, gender, and severity of illness.
Conclusions: An increased number of circulating endothelial progenitor cells in acute
lung injury is associated with improved survival.
Key words: stem cells, acute respiratory distress syndrome, outcomes, endothelium, mortality
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