VEGF coordinates interaction of pericytes and endothelial cells during vasculogenesis and experimental angiogenesis

Abstract

Biological activities of vascular endothelial growth factor (VEGF) have been studied extensively in endothelial cells (ECs), but few data are available regarding its effects on pericytes. In murine embryoid body cultures, VEGF-induced expression of desmin and ␣-smooth muscle actin (␣-SMA) in CD-31 ϩ cells. The number of CD-31 ϩ /desmin ϩ vascular chords increased with VEGF treatment time and peaked during a differentiation window between 6 and 9 days after plating. In vivo, VEGF-induced elongation and migration of desmin-positive pericytes and coverage of angiogenic capillaries, as revealed by analysis of Sambucus nigra lectin-stained vascular beds of the chick chorioallantoic membrane. VEGF also caused significant decrease of intercapillary spaces, an indicator for intussusceptive vascular growth. These VEGF-mediated effects point at a more intricate interaction between ECs and pericytes cells than previously demonstrated and suggest that pericytes may be derived from EC progenitors in vitro and not only stabilize capillaries but also participate in vascular remodeling in vivo.

The Human Mesenchymal Stem Cells and the Chick Embryo Chorioallantoic Membrane: The Key and the Lock in Revealing Vasculogenesis

“…It is clear that SMA is needed for the stability of the pseudopode like projections present in the pericytes (16), offering a consecutive stability to the vessel wall, but the question is why is this SMA expressed so early in the cMSC? It was hypothesized that pericytes are recruited towards the capillary plexus early in CAM development (before day 10 of incubation) (16) and VEGF seems to stimulate this process (17). Our results regarding the hMSC-stimulated vasculogenic process prove something else.…”

“…All these cells show a mesenchymal morphology, so that we suggest that the mesenchymal stem cell represents the common progenitor for both CD34 + and SMA + cells involved in the new vessel formation. This idea is sustained by the results of Hagedorn et al who promote the idea of a synchronized differentiation of the different cellular components of blood vessels, as they observed that after the VEGF stimulation of embryonic bodies, groups of cells expressing both endothelial and pericyte antigens got engaged in a cord formation process (17).…”

Intussusceptive angiogenesis: Its emergence, its characteristics, and its significance

“…On the other hand, older and recently published articles by Wilting and coworkers indicated that local application of VEGF-induced intussusceptive vascular growth in the chick CAM (Wilting et al, 1996;Hagedorn et al, 2004). These apparent controversial results could be explained by the existence of gradients in the growth factor distribution.…”

“…They are, however, awaiting a more precise characterization. Recent work by Hagedorn and coworkers (Hagedorn et al, 2004) suggests that they could belong to the pericytic cell population.…”

“…As observed in the lung and in the CAM, the pericytes and the endothelial-like cells, respectively, seem to play a role in initiating the pillar formation and also in stabilizing the pillar core possibly by the synthesis of extracellular matrix proteins. Interestingly, it has been shown that vascular endothelial growth factor (VEGF) induced the differentiation and recruitment of pericytes in the chick CAM during its growth phase (Hagedorn et al, 2004).…”