Tips, Stalks, Tubes: Notch-Mediated Cell Fate Determination and Mechanisms of Tubulogenesis during Angiogenesis

Exosomes secreted by mesenchymal stem cells promote endothelial cell angiogenesis by transferring miR-125a

“…Previous studies have indicated that DLL4 regulates endothelial cell sprouting during angiogenesis by inhibiting endothelial tip cell formation (Tung et al, 2012). In order to confirm that adMSC- Exo and miR-125a modulated angiogenesis through DLL4, we examined the DLL4 protein expression level and tip cell formation of HUVECs either exposed to adMSC-Exo or transfected with miR125a mimic.…”

“…Among the predicted candidates, we focused on DLL4, a ligand of Notch signaling pathway, which has been proven to repress angiogenesis (Tung et al, 2012). According to the computational analysis, the miR-125a target site in the 3′UTR of DLL4 is highly conserved among vertebrates and partially complementary to miR-125a (Fig.…”

The Hematopoietic Chemokine CXCL12 Promotes Integration of Human Endothelial Colony Forming Cell–Derived Cells into Immature Vessel Networks

“…Once the tip cells anastomose or inosculate with other tip cells [23], vessel maturation takes place and this involves mural cell recruitment, extracellular matrix deposition, and the commencement of blood flow. A key feature of vasculogenesis and angiogenesis is central vascular lumen formation, the complexity of which has recently been reviewed [24][25][26][27]. The cord hollowing model of lumenization highlights the importance of interendothelial junctions and apicobasal polarity.…”

“…Multicellular endothelial cell cords form, migrate into the stroma, lose apicobasal polarity and cord junctions, and increase to two or three cell thicknesses. Subsequently, endothelial cell repulsion, junctional rearrangements, and change in shape of endothelial cells result in unicellular tube formation [25][26][27].…”

Notching up vascular regeneration

“…The Notch signaling pathway is a well-established regulator of mature ECs [6]. Inactivation of Notch ligands or receptors causes lethal vascular defects in developing embryos.…”