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(Stroke. 2008;39:1441.)
© 2008 American Heart Association, Inc.

Original Contributions

Circulating Endothelial Progenitor Cells as a New Marker of Endothelial Dysfunction or Repair in Acute Stroke

Kon Chu, MD, PhD; Keun-Hwa Jung, MD; Soon-Tae Lee, MD; Hee-Kwon Park, MD; Dong-In Sinn, MD; Jeong-Min Kim, MD; Dong-Hyun Kim, MS; Jin-Hee Kim, MS; Se-Jeong Kim, MS; Eun-Cheol Song, MD; Manho Kim, MD, PhD; Sang Kun Lee, MD, PhD Jae-Kyu Roh, MD, PhD

From the Neural Stem Cell Laboratory in Clinical Research Institute (A.-K.C., K.-H.J., S.-T.L., H.-K.P., D.-I.S., J.-M.K., D.-H.K., J.-H.K., S.-J.K., E.-C.S., M.K., S.K.L., J.-K.R.), Stem Cell Research Center, Department of Neurology, Seoul National University Hospital, Program in Neuroscience, Neuroscience Research Institute of SNUMRC, Seoul National University, Seoul, Korea; the Division of Epidemic Intelligence Service (K.-H.J.), Korea Center for Disease Control & Prevention, Seoul, Korea; and the Department of Neurology (E.-C.S.), Inha University Hospital, Incheon, South Korea.

Correspondence to Jae-Kyu Roh, MD, PhD, Department of Neurology, Seoul National University Hospital, 28, Yongon-dong, Chongro-gu, Seoul, 110-744, South Korea. E-mail rohjk{at}snu.ac.kr

Background and Purpose— Understanding on distinct subsets of endothelial progenitor cells may provide insights of endothelial dysfunction or repair in the acute ischemic event. Recent in vitro data have reported the colony-forming unit (CFU) and outgrowth cell population as a subset of endothelial progenitor cells. In this study, we undertook to validate the significance of CFU number and outgrowth cell yield in acute stroke.

Methods— Mononuclear cells were isolated from the peripheral blood of 75 patients with acute stroke, 45 patients with chronic stroke, and 40 age-matched healthy volunteers. CFU numbers were counted after culturing them for 7 days, and outgrowth cell appearance was measured during the 2 months of culture. Endothelial progenitor cell function was also evaluated by matrigel plate assays. Independent parameters predicting CFU number and outgrowth cell yield were assessed using logistic regression analysis.

Results— The CFU numbers and tube formation abilities in matrigel assays were significantly reduced in patients with acute stroke compared with patients with chronic stroke or healthy control subjects. Moreover, patients with large artery atherosclerosis had much lower CFU numbers and functional activities than ones with cardioembolism. Outgrowth cells were isolated from 10% of healthy control subjects and 22% of patients with chronic stroke during the cultures, but from 71% of patients with stroke. Multivariate analysis identified glycosylated hemoglobin and National Institutes of Health Stroke Scale on admission as significant independent predictors of a low CFU number and a high isolation frequency of outgrowth cells, respectively.

Conclusion— CFU number may thus represent an accumulated endothelial progenitor cell dysfunctional status, whereas outgrowth cell appearance may reflect the resilience of the systemic circulation to acute ischemic stress.

Supplemental Methods