Circulating endothelial progenitor cells as a new marker of endothelial dysfunction or repair in acute stroke.
OBJECTIVE
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.


CONCLUSIONS
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.
Chu
Kon
K
Stem Cell Research Center, Department of Neurology, Seoul National University Hospital, Neuroscience Research Institute of SNUMRC, Seoul National University, Seoul, Korea.
Jung
Keun-Hwa
KH
Lee
Soon-Tae
ST
Park
Hee-Kwon
HK
Sinn
Dong-In
DI
Kim
Jeong-Min
JM
Kim
Dong-Hyun
DH
Kim
Jin-Hee
JH
Kim
Se-Jeong
SJ
Song
Eun-Cheol
EC
Kim
Manho
M
Lee
Sang Kun
SK
Roh
Jae-Kyu
JK
D000208:Acute Disease; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D002545:Brain Ischemia / Q000175:diagnosis / Q000503:physiopathology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D002536:Cerebral Arteries / Q000166:cytology* / Q000503:physiopathology; D003094:Collagen; D003114:Colony-Forming Units Assay / Q000379:methods; D004338:Drug Combinations; D042783:Endothelial Cells / Q000166:cytology* / Q000502:physiology; D005260:Female; D006801:Humans; D007797:Laminin; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic / Q000502:physiology; D011237:Predictive Value of Tests; D011379:Prognosis; D011509:Proteoglycans; D012016:Reference Values; D012038:Regeneration; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology; D020521:Stroke / Q000175:diagnosis / Q000503:physiopathology*
D015415:Biomarkers; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen