Cytokine-Like 1 Is a Novel Proangiogenic Factor Secreted by and Mediating Functions of Endothelial Progenitor Cells

Rationale: Endothelial colony forming cells (ECFCs) or late blood outgrowth endothelial cells (BOECs) can be isolated from human cord or peripheral blood, display properties of endothelial progenitors, home into ischemic tissues and support neovascularization in ischemic disease models. Objective: To assess the functions of cytokine-like 1 (CYTL1), a factor we found preferentially produced by ECFCs, in regard of vessel formation. Methods and Results: We show by transcriptomic analysis that ECFCs are distinguished from endothelial cells of the vessel wall by production of high amounts of CYTL1. Modulation of expression demonstrates that the factor confers increased angiogenic sprouting capabilities to ECFCs and can also trigger sprouting of mature endothelial cells. The data further display that CYTL1 can be induced by hypoxia and that it functions largely independent of VEGF-A. By recombinant production of CYTL1 we confirm that the peptide is indeed a strong pro-angiogenic factor and induces sprouting in ...