Stem and progenitor cells from peripheral blood

Published on March 5, 2014   45 min
0:00
Hello, my name is Shay Soker, and I'm a professor at the Wake Forest Institute for Regenerative Medicine. I'll be talking today about stem and progenitor cells from peripheral blood.
0:14
The bone marrow is, most likely, the source of stem and progenitor cells in peripheral blood. Hemangioblasts are the embryonic precursors of the hematopoietic stem cells, or HSCs, and they would give rise to the committed hematopoietic cells. Bone marrow mesenchymal cells, or MSCs, have multi-lineage differentiation potentials. Endothelial progenitor cells, or EPCs, are probably derived from hemangioblast precursors of hematopoietic stem cells, but they differentiate into endothelial cells, or ECs. My lecture will focus on EPCs and their role in neo-vascularization
0:58
As a definition, I want to highlight two processes. The first is angiogenesis- - the process of forming of new vessels from pre-existing blood vessels. The second one is vasculogenesis- - the assembly of capillaries from endothelial progenitor cells. And I will discuss during the lecture, the physiologic neo-vascularization and pathologic neo-vascularization.
1:27
The embryonic development of the vasculature, as I told you before- - it starts with the primary hepatoblasts that differentiates into angioblasts. These angioblasts will further go and differentiate into endothelial cells to form the primitive plexus, and under the induction of other angiogenic prospectus, which we'll be discussing later on, they form the mature vascular system. Once this vascular system is formed, it stays quiescent under another set of growth factors, one of which is angiopoietin-1, or ANG-1. Now, the process of angiogenesis and vasculogenesis also occurs during adult life but is mostly restricted to angiogenesis. Upon stimulation using growth factors such as angiopoietin-2 and VEGF, the endothelial cells are activated, and then they form new vessels. Recently- - and that's going to be the topic of this lecture- - it was shown that the immature hemangioblasts and angioblasts may also contribute to adult neo-vascularization.
2:44
Let's first discuss and describe the endothelial cells. Endothelial cells are the cells that line the lumen of the blood vessel. On the left hand side, we can see a mature blood vessel. Endothelial cells are in the center lining the lumen. They're surrounded or supported by an internal elastic lamina. Around this elastic lamina, we have several layers, depending on the size of the blood vessels of smooth muscle cells, and these smooth muscle cells are supported by the tunica adventitia, a connective tissue. Endothelial cells are characterized by a cell surface marker. These are proteins that are expressed on the cells, on the membrane of the endothelial cells. Among these, the common ones that are being used to characterize endothelial cells are CD31 PECAM; CD33; CD105, or endoglin; CD146-- may sometimes be listed as P1H12 or MUC18; Von Willebrand Factor; VEGF receptors, and so on. We will use some of these markers in the next slides.
4:03
Here, we see the molecular mechanism of angiogenesis. At first, the endothelial cells are being activated by angiogenic growth factors. We will discuss a list of these growth factors in later slides, but two of them are listed here; fibroblast growth factor, FGF, and vascular endothelial growth factor, VEGF. These growth factors find specific receptors on the endothelial cells and activate the endothelial cells. Upon activation, the endothelial cells are separating a set of enzymes, among which are the matrix metalloproteinase, or MMPs, that degrade the base membrane vein that's surrounding the endothelial cells. Upon degradation, the endothelial cells can migrate out, and they use integrin, such as alpha-v beta-3 integrins, to help them to migrate out and form the new capillaries in stage four. These new capillaries are also supported by parasites that will later on give rise to the smooth muscle cells. And these parasites are being recruited upon growth factors that are being secreted from other cells in the area, such as mesenchymal cells. These parasites are communicating with the endothelial cells through different growth factors, one of which is the PDGF, or platelet derived growth factor. The receptor is found on the parasites and the endothelial cells secrete the growth factor in order to recruit those parasites to the endothelial cells to form a mature vessel.
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Stem and progenitor cells from peripheral blood

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