Vascular Endothelium - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 470

9.3.2.1 Early and Late Endothelial Progenitors

Two populations of endothelial progenitor cells exist — early and late endothelial
progenitors — with distinct growth patterns and secretion modalities of angiogenic
factors. Spindle-shaped early endothelial progenitors are also called early-outgrowth
endothelial progenitors, early-outgrowth culture-expanded endothelial progenitor
cells, endothelial cell-like cells, colony-forming unit (CFU) of endothelial cells,
circulating angiogenic cells, attaching cells, and culture-modified mononuclear
cells [ 870 ].
In fact, this population of endothelial progenitor cells can be subdivided into
2 classes. The first reported progenitor cell type — the colony-forming unit-Hill
cells — originates from cultures of non-adherent peripheral blood mononuclear cells
that are not able to form vascular structures in vivo [ 873 ]. Circulating angiogenic
cells — early-outgrowth cells — are descendants of the monocyte-macrophage
subset and operate in initiation of angiogenesis during wound healing and tis-
sue remodeling [ 873 ]. Early-outgrowth endothelial progenitors express VEGFR2,
PECAM1, cadherin-5, CD34 (generally at a low level), and von Willebrand
factor, as well as monocytic marker CD14 (bacterial lipopolysaccharide receptor
component) and panleukocytic marker PTPRc [ 870 ]. 23
Late endothelial progenitor cells are also named late-outgrowth endothelial
progenitors, endothelial colony-forming cells (ECFC), and blood-derived outgrowth
endothelial cells. They start to proliferate only after 2 to 3 weeks in culture [ 870 ],
but possess a high proliferative capacity [ 873 ]. These cells can spontaneously form
blood vessels. They express all typical properties of endothelial cells. They express
endothelial markers, like VEGFR2, melanoma cell adhesion molecule (MCAM or
CD146), and cadherin-5, in addition to CD34, but not hematopoietic markers, such
as PTPRc and monocyte differentiation antigen CD14 [ 870 ].
Circulating endothelial progenitor cells that include cells that generate both
early- and late-outgrowth endothelial progenitors may be represented by CD34

+ ,

VEGFR2 cells [ 870 ].

Hemangioblasts do not possess receptor protein Tyr phosphatase PTPRc
(or CD45), a common leukocyte antigen. Circulating endothelial progenitors are
defined by markers, such as VEGFR2, hematopoietic progenitor cell glycoprotein
and intercellular adhesion factor CD34, PTPRc, and pentaspan transmembrane
glycoprotein prominin-1. 24 Monocytes can also provide a source of endothelial
progenitors that do not proliferate, but release angiogenic growth factors.

+

23 Molecule CD14 serves as a component of the bacterial lipopolysaccharide receptor with TLR4
and lymphocyte antigen Ly96. Endothelial cells express both CD14 and TLR4, but to a lower
extent than monocytes and macrophages. Lipopolysaccharides can then bind to endothelial cells
and upregulate ahesion molecules and coagulation factors.
24 Prominin-1, a.k.a. CD133 and AC133, is a primitive hematopoietic stem cell marker that is
not produced by mature endothelial cells. Both endothelial progenitors and mature endothelial
cells express similar endothelial-specific markers, such as VEGFR2, TIE1, TIE2, and VE-
cadherin (a.k.a. Cdh5 and CD144). Subpopulations of monocytes, macrophages, lymphocytes, and