Browsing by Subject "vasculogenesis"

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    Endothelial stem and progenitor cells (stem cells): (2017 Grover Conference Series)
    (SAGE, 2017-11-03) Yoder, Mervin C.; Pediatrics, School of Medicine
    The capacity of existing blood vessels to give rise to new blood vessels via endothelial cell sprouting is called angiogenesis and is a well-studied biologic process. In contrast, little is known about the mechanisms for endothelial cell replacement or regeneration within established blood vessels. Since clear definitions exist for identifying cells with stem and progenitor cell properties in many tissues and organs of the body, several groups have begun to accumulate evidence that endothelial stem and progenitor cells exist within the endothelial intima of existing blood vessels. This paper will review stem and progenitor cell definitions and highlight several recent papers purporting to have identified resident vascular endothelial stem and progenitor cells.
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    Epigenetic Activation of Pro-angiogenic Signaling Pathways in Human Endothelial Progenitors Increases Vasculogenesis
    (Cell Press, 2017-10-12) Fraineau, Sylvain; Palii, Carmen G.; McNeill, Brian; Ritso, Morten; Shelley, William C.; Prasain, Nutan; Chu, Alphonse; Vion, Elodie; Rieck, Kristy; Nilufar, Sharmin; Perkins, Theodore J.; Rudnicki, Michael A.; Allan, David S.; Yoder, Mervin C.; Suuronen, Erik J.; Brand, Marjorie; Pediatrics, School of Medicine
    Human endothelial colony-forming cells (ECFCs) represent a promising source of adult stem cells for vascular repair, yet their regenerative capacity is limited. Here, we set out to understand the molecular mechanism restricting the repair function of ECFCs. We found that key pro-angiogenic pathways are repressed in ECFCs due to the presence of bivalent (H3K27me3/H3K4me3) epigenetic marks, which decreases the cells' regenerative potential. Importantly, ex vivo treatment with a combination of epigenetic drugs that resolves bivalent marks toward the transcriptionally active H3K4me3 state leads to the simultaneous activation of multiple pro-angiogenic signaling pathways (VEGFR, CXCR4, WNT, NOTCH, SHH). This in turn results in improved capacity of ECFCs to form capillary-like networks in vitro and in vivo. Furthermore, restoration of perfusion is accelerated upon transplantation of drug-treated ECFCs in a model of hindlimb ischemia. Thus, ex vivo treatment with epigenetic drugs increases the vascular repair properties of ECFCs through transient activation of pro-angiogenic signaling pathways., • Pro-angiogenic pathways are maintained in a poised state in ECFCs • Epigenetic drugs resolve bivalently marked genes toward an active state in ECFCs • Treatment with epigenetic drugs activates multiple pro-angiogenic pathways in ECFCs • Ex vivo treatment with epigenetic drugs increases ECFC-mediated vasculogenesis , Endothelial colony-forming cells (ECFCs) have the unique capability to form blood vessels in vivo. Here, Brand and colleagues show that the regenerative function of ECFCs is restricted by the presence of bivalent histone marks on pro-angiogenic genes. This poised status can be overcome through the combined action of epigenetic drugs that simultaneously activate multiple pro-angiogenic pathways to increase ECFC-mediated vasculogenesis.