Nestin is a New Partner in Endothelial Colony Forming Cell Angiogenic Potential

Nestin, an intermediate filament protein expressed by progenitor cells, is associated with tissue regeneration. Although nestin expression has been reported in poorly differentiated and newly formed blood vessels, its role in endothelial cells remains unclear. In this study, we investigated the involvement of nestin in the angiogenic properties of endothelial colony-forming cells (ECFCs) derived from human umbilical cord blood. Our results demonstrate that ECFCs express high levels of nestin, and that its inhibition by small interfering RNAs decreased ECFC proliferation, migration in response to SDF-1 and VEGF-A, tubulogenesis, and adhesion on collagen. These effects are associated with modulation of focal adhesion kinase phosphorylation. Furthermore, nestin silencing resulted in reduced revascularization in a mouse hindlimb ischemia model. In conclusion, these findings provide evidence that nestin more than being a structural protein, is an active player in ECFC angiogenic properties. Graphical Abstract