Origins of circulating endothelial cells and endothelial outgrowth from blood

TLDR

Normal adults contain only a few circulating endothelial cells (CEC) in peripheral blood, and endothelial outgrowth can be induced from blood cultures. The study aimed to determine the cellular origins of CEC and of endothelial outgrowth derived from blood cultures. Fluorescence in situ hybridization of blood from gender‑mismatched bone‑marrow transplant recipients showed that fresh CEC are mainly recipient‑derived, whereas endothelial outgrowth after about a month becomes predominantly donor‑derived, indicating that vessel‑wall cells give rise to CEC with limited expansion while marrow‑derived angioblasts drive the extensive proliferation seen in culture.

Abstract

Normal adults have a small number of circulating endothelial cells (CEC) in peripheral blood, and endothelial outgrowth has been observed from cultures of blood. In this study we seek insight into the origins of CEC and endothelial outgrowth from cultures of blood. Fluorescence in situ hybridization analysis of blood samples from bone marrow transplant recipients who had received gender-mismatched transplants 5–20 months earlier showed that most CEC in fresh blood had recipient genotype. Endothelial outgrowth from the same blood samples after 9 days in culture (5-fold expansion) was still predominately of the recipient genotype. In contrast, endothelial outgrowth after ∼1 month (102-fold expansion) was mostly of donor genotype. Thus, recipient-genotype endothelial cells expanded only ∼20-fold over this period, whereas donor-genotype endothelial cells expanded ∼1000-fold. These data suggest that most CEC in fresh blood originate from vessel walls and have limited growth capability. Conversely, the data indicate that outgrowth of endothelial cells from cultures of blood is mostly derived from transplantable marrow-derived cells. Because these cells have more delayed outgrowth but a greater proliferative rate, our data suggest that they are derived from circulating angioblasts.