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CLINICAL RESEARCH: ENDOTHELIAL PROGENITOR CELLS

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

Thomas J. Povsic, MD, PhD^_*,_*, Katherine L. Zavodni, BS^_*, Francine L. Kelly, BS^_*, Shoukang Zhu, PhD^_*, Pascal J. Goldschmidt-Clermont, MD, FACC, Chunming Dong, MD^_* and Eric D. Peterson, MD, MPH, FACC

^_* Division of Cardiology, Duke University Medical Center, Durham, North Carolina
Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina
Miller School of Medicine, University of Miami, Miami, Florida

Manuscript received April 9, 2007; revised manuscript received August 23, 2007, accepted August 27, 2007.

^_* Reprint requests and correspondence: Dr. Thomas J. Povsic, Box 3126, Duke University Medical Center, Durham, North Carolina 27710. (Email: povsi001{at}mc.duke.edu).

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.

Abbreviations and Acronyms   ALDH = aldehyde dehydrogenase   ALDHbr = aldehyde dehydrogenase-bright   CAD = coronary artery disease   EPC = endogenous progenitor cell   FACS = fluorescence-activated cell sorting   MNC = mononuclear cell   VEGFR = vascular endothelial growth factor receptor

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