CD34−Blood‐Derived Human Endothelial Cell Progenitors

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Abstract
A subset of adult peripheral blood leukocytes functions as endothelial cell progenitors called angioblasts. They can incorporate into the vasculature in animal models of neovascularization and accelerate the restoration of blood flow to mouse ischemic limbs. Earlier reports suggested that CD34‐expressing (CD34+) but not CD34+ cell‐depleted (CD34−) leukocytes can differentiate into endothelial cells (EC) in vitro and in vivo. Recent findings suggest that CD14+ cells, which are typically CD34−, also have angioblast‐like properties in vitro. To determine the identity of angioblasts, the potential of CD34+, CD34−, CD34−CD14+, and CD34−CD14− cells to produce EC was compared. We show that a subset of monocyte (CD34−CD14+)‐enriched cells can take on an EC‐like phenotype in culture, but that the EC‐like cells also express dendritic cell antigens. These findings suggest that monocytes differentiate into macrophages, dendritic cells, or EC depending on environmental cues. The data also demonstrate that angioblasts are more abundant in the blood than previously thought. Finally, we demonstrate that CD34− and CD34−CD14+ cells incorporate into the endothelium of blood vessels in mouse ischemic limbs. However, incorporation of these cells requires co‐injection with CD34+ cells, indicating that leukocyte‐leukocyte interactions may play a critical role in governing angioblast behavior in vivo.