An intimate interplay between precocious, migrating pericytes and endothelial cells governs human fetal brain angiogenesis

Abstract

In order to better understand the process of angiogenesis in the developing human brain, we have examined the spatial relationship and relative contributions of endothelial cells and pericytes, the two primary cell types involved in vessel growth, together with their relation with the vascular basement membrane. Pericytes were immunolocalized through use of the specific markers nerve/glial antigen 2 (NG2) proteoglycan, endosialin (CD248) and the platelet-derived growth factor receptor beta (PDGFR-beta), while endothelial cells were identified by the pan-endothelial marker CD31 and the blood brain barrier (BBB)-specific markers claudin-5 and glucose transporter isoform 1 (GLUT-1). The quantitative analysis demonstrates that microvessels of the fetal human telencephalon are characterized by a continuous layer of activated/angiogenic NG2 pericytes, which tightly invest endothelial cells and participate in the earliest stages of vessel growth. Immunolabelling with anti-active matrix metalloproteinase-2 (aMMP-2) and anti-collagen type IV antibodies revealed that aMMP-2 producing endothelial cells and pericytes are both associated with the vascular basement membrane during vessel sprouting. Detailed localization of the two vascular cell types during angiogenesis suggests that growing microvessels of the human telencephalon are formed by a pericyte-driven angiogenic process in which the endothelial cells are preceded and guided by migrating pericytes during organization of the growing vessel wall.

Human mesenchymal stem cells from bone marrow express tumor endothelial and stromal markers

“…Although endosialin was described to be a tumor endothelial marker implying selective endothelial cell expression for endosialin, expression of endosialin has been documented in other cell types (11). Endosialin has been detected in fibroblasts, perivascular in the tumor microenvironment and mesenchymal malignant cells (14,16,21,41,46).…”

Early Inhibition of MMP Activity in Ischemic Rat Brain Promotes Expression of Tight Junction Proteins and Angiogenesis During Recovery

“…15 The transmembrane proteoglycan, NG2, identifies pericytes in angiogenic microvasculature. 16 Colabeling with NG2 and RECA1 showed low NG2 signal in sham-operated and contralateral hemispheres at 3 weeks after stroke. However, NG2-positive pericytes were seen around vessels identified by RECA1 in the peri-infarct areas ( Figure 2A).…”

Hypoxia upregulates expression of human endosialin gene via hypoxia-inducible factor 2

“…Moreover, abundant endosialin expression was found in the vasculature and fibroblast-like cells of the developing mouse and human embryos (Rupp et al, 2006;MacFadyen et al, 2007;Virgintino et al, 2007). Using a gene targeting approach, Nanda et al (2006) have shown that endosialin is dispensable for normal development and subcutaneous tumour growth, but can modulate invasiveness and metastatic progression in an orthotopic xenograft model of colorectal cancer.…”