On the origin of (CD105+) circulating endothelial cells.

ABSTRACT

Cells designated by the CellSearch assay as circulating endothelial cells (CEC) (CD146 (+)/CD105 (+)/ CD45(-) nuclear cells) are thought to derive from damaged vasculature. As CD105 has been suggested to be expressed by endothelial cells from malignant vasculature particularly, it is currently unknown whether this assay is suitable to determine CECs in non-malignant diseases. Also, more insight is needed whether CECs as detected by this assay predominantly measures CECs or also endothelial progenitor cells (EPCs), which originate from the bone marrow and reflect angiogenesis rather than vascular damage. CEC counts were determined in nine patients treated with isolated limb perfusion with tumour necrosis factor (TNF) a and melphalan, and in 10 healthy donors. Given the severe vascular damage caused by venesection and cannulation of the main vessels, we expected a significant increase in CEC counts in case CEC were of vascular rather than of bone marrow origin. Additionally, this finding, as well as the presence of CD105 (+) CEC in the blood of healthy controls, would confirm that healthy endothelial cells express CD105. Numbers of CD146 (+)/CD105 (+)/CD45(-) nuclear CEC increased significantly after venesection and cannulation. After administration of TNF, a large fraction of non-intact, possibly apoptotic CEC appeared. This study shows that the Cell-Search assay detects CECs originating from damaged vasculature. Furthermore, CD105 expression is found on CEC from damaged normal vasculature rendering further exploration of the value of CEC determined by this assay worthwhile not only in malignant diseases but also in non malignant disorders characterised by vascular damage.