Circulating progenitor cells can be reliably identified on the basis of aldehyde dehydrogenase activity.
OBJECTIVE
Our objective was to develop and assess a novel endogenous progenitor cell (EPC) assay based on aldehyde dehydrogenase (ALDH) activity, and to define the relationship of ALDH-bright (ALDH(br)) cells with previously defined EPCs, patient age, and extent of coronary artery disease.


BACKGROUND
Accurate assessment of circulating EPCs is of significant interest, yet current assays have limitations. Progenitor cells display high levels of ALDH activity. An assay based on ALDH activity may offer a simple means for enumerating EPCs.


METHODS
We simultaneously determined the numbers of EPCs based on ALDH activity and cell surface expression of CD133, CD34, and vascular endothelial growth factor receptor-2 in 110 patients undergoing cardiac catheterization. We assessed the reproducibility of these estimates, correlation among EPC assays, and the association of ALDH(br) numbers with age and disease severity.


RESULTS
Aldehyde dehydrogenase-bright cells were easily identified in nonmobilized peripheral blood with median and mean frequencies of 0.041% and 0.074%, respectively. Aldehyde dehydrogenase-bright cells expressed CD34 or CD133 cell surface markers (57.0% and 27.1%, respectively), correlated closely with CD133+CD34+ cells (r = 0.72; p < 0.001), and differentiated into endothelial cells with greater efficiency than CD133+CD34+ cells. Aldehyde dehydrogenase-bright cell numbers were inversely associated with patient age and coronary disease severity.


CONCLUSIONS
Aldehyde dehydrogenase activity represents a novel simplified method for quantifying EPCs. The correlation of ALDH(br) cells with clinical factors and outcomes warrants further study.
Division of Cardiology, Duke University Medical Center, Durham, North Carolina 27710, USA. povsi001@mc.duke.edu
Thomas J
TJ
Povsic
Katherine L
KL
Zavodni
Francine L
FL
Kelly
Shoukang
S
Zhu
Pascal J
PJ
Goldschmidt-Clermont
Chunming
C
Dong
Eric D
ED
Peterson
D000071916:AC133 Antigen; D000367:Age Factors; D000368:Aged; D000444:Aldehyde Dehydrogenase / Q000378:metabolism*; D015703:Antigens, CD / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism; D006328:Cardiac Catheterization; D002452:Cell Count / Q000379:methods*; D003324:Coronary Artery Disease / Q000097:blood / Q000201:enzymology* / Q000473:pathology; D005260:Female; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000378:metabolism; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D013234:Stem Cells / Q000201:enzymology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D000444:Aldehyde Dehydrogenase; D040301:Vascular Endothelial Growth Factor Receptor-2