Published Online
on August 30, 2007

A more recent version of this article appeared on October 1, 2007

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Submitted on February 2, 2007
Revised on March 28, 2007
Accepted on April 12, 2007

The Increase of Circulating Endothelial Progenitor Cells After Acute Ischemic Stroke Is Associated With Good Outcome

Tomás Sobrino PhD; Olivia Hurtado PhD; María Ángeles Moro PhD; Manuel Rodríguez-Yáñez MD, PhD; Mar Castellanos MD, PhD; David Brea BSc; Octavio Moldes BSc; Miguel Blanco MD, PhD; Juan F. Arenillas MD, PhD; Rogelio Leira MD, PhD; Antonio Dávalos MD, PhD; Ignacio Lizasoain MD, PhD; and José Castillo MD, PhD^*

From the Clinical Neuroscience Research Laboratory (T.S., O.H., M.R.-Y., D.B., O.M., M.B., R.L., J.C.), Department of Neurology, Hospital Clínico Universitario, University of Santiago de Compostela, Santiago de Compostela, Spain; Department of Pharmacology (M.A.M., I.L.), School of Medicine, University Complutense, Madrid, Spain; Department of Neurology (M.C.), Hospital Doctor Josep Trueta, Girona, Spain; Department of Neurosciences (J.F.A., A.D.), Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Spain.

^* To whom correspondence should be addressed. E-mail: mecasti{at}usc.es.

Background and Purpose—Increased circulating endothelial progenitor cells (EPC) have been associated with a low cardiovascular risk and may be involved in endothelial cell regeneration. The present study was designed to evaluate the prognostic value of EPC in acute ischemic stroke.

Methods—Forty-eight patients with a first-ever nonlacunar ischemic stroke were prospectively included in the study within 12 hours of symptoms onset. Stroke severity was evaluated by the National Institutes of Health Stroke Scale, and functional outcome was assessed at 3 months by the modified Rankin Scale (mRS). Infarct volume growth between admission and days 4 to 7 was measured on multiparametric MRI. EPC colonies were defined as early outgrowth colony-forming unit-endothelial cell (CFU-EC). The increment of CFU-EC was quantified during the first week and defined as the absolute difference between the number of CFU-EC at day 7 and admission. The influence of CFU-EC increase on good functional outcome (mRS 2) and infarct growth was analyzed by logistic regression and linear models.

Results—Patients with good outcome (n=25) showed a higher CFU-EC increment during the first week (median [quartiles], 23 [11, 36] versus -3 [-7, 1], P<0.0001) compared with patients with poor outcome. CFU-EC increment 4 during the first week was associated with good functional outcome at 3 months (odds ratio, 30.7; 95% CI, 2.4 to 375.7; P=0.004) after adjustment for baseline stroke severity, ischemic volume and thrombolytic treatment. For each unit increase in the CFU-EC the mean reduction in the growth of infarct volume was 0.39 (0.03 to 0.76) mL (P=0.033).

Conclusions—The increase of circulating EPC after acute ischemic stroke is associated with good functional outcome and reduced infarct growth. These findings suggest that EPC might participate in neurorepair after ischemic stroke.

Key words: endothelial progenitor cells • ischemic stroke • neovascularization • neurorepair

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