Circulating Progenitor Cells Can Be Reliably Identified on the Basis of Aldehyde Dehydrogenase Activity

Objectives: 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.