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.
The bone marrow is,
most likely, the source
of stem and progenitor
cells in peripheral blood.
Hemangioblasts are the
of the hematopoietic
stem cells, or HSCs,
and they would give rise to the
committed hematopoietic cells.
Bone marrow mesenchymal
cells, or MSCs,
cells, or EPCs,
are probably derived from
stem cells, but they
endothelial cells, or ECs.
My lecture will focus on EPCs and
their role in neo-vascularization
As a definition, I want to
highlight two processes.
The first is angiogenesis- -
the process of forming of new
vessels from pre-existing
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.
The embryonic development of the
vasculature, as I told you before-
- it starts with the
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.
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
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.
Here, we see the molecular
mechanism of angiogenesis.
At first, the endothelial
cells are being
activated by angiogenic
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
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.