Origin of endothelial progenitors in human postnatal bone marrow

Abstract

This study demonstrates that a CD34–, vascular endothelial cadherin– (VE-cadherin–), AC133+, and fetal liver kinase+ (Flk1+) multipotent adult progenitor cell (MAPC) that copurifies with mesenchymal stem cells from postnatal human bone marrow (BM) is a progenitor for angioblasts. In vitro, MAPCs cultured with VEGF differentiate into CD34+, VE-cadherin+, Flk1+ cells — a phenotype that would be expected for angioblasts. They subsequently differentiate into cells that express endothelial markers, function in vitro as mature endothelial cells, and contribute to neoangiogenesis in vivo during tumor angiogenesis and wound healing. This in vitro model of preangioblast-to-endothelium differentiation should prove very useful in studying commitment to the angioblast and beyond. In vivo, MAPCs can differentiate in response to local cues into endothelial cells that contribute to neoangiogenesis in tumors. Because MAPCs can be expanded in culture without obvious senescence for more than 80 population doublings, they may be an important source of endothelial cells for cellular pro- or anti-angiogenic therapies

MAPK/ERK1/2 signaling mediates endothelial-like differentiation of immature DCs in the microenvironment of esophageal squamous cell carcinoma

“…It has traditionally been believed that tumor vascularization is ascribed to the sprouting of ECs from existing vessels, however recent studies indicate that the recruitment of endothelial progenitors that differentiate into ECs plays an important role in the formation of tumor neovessels [49][50][51]. DCs and their precursors might contribute to new vessel formation by two possible mechanisms: by stimulating angiogenesis from existing vessels through the release of pro-angiogenic factors [52,53], or by contributing to vasculogenesis by trans-differentiation into ELCs.…”

The role of endoglin in post-ischemic revascularization

“…EPCs, both circulating and resident, can then differentiate into mature ECs that line the lumen of blood vessels and/or release growth factors that act in a paracrine manner to support the endothelium. EPCs are thus thought to function in angiogenesis and as a reservoir for the replacement of dysfunctional or senescent ECs to maintain the existing vessel walls [176,177].…”

Circulating Osteogenic Cells

“…For example, a common progenitor (termed "mesangioblasts") that can differentiate into endothelial and mesodermal cells (osteoblasts, adipocytes, myocytes) has been isolated in cultures of embryonic dorsal aorta [29,30] as Flk1 + CD34 + VE-cadherin + alpha smooth muscle + cells [29,30] . Some studies suggest the presence of a counterpart for this cell population in the bone marrow of postnatal organisms [31,32] .…”