Biomedical Engineering Reference
In-Depth Information
1.3.
Stem cell-ECM interactions in the niche
Stem cells in the niche also interact via specific receptors such as integrins with
their surrounding ECM
(Fig. 1a and 1b)
The ECM can be either a 2-dimensional
(2D) or a 3-dimensional (3D) crosslinked network of proteins and sugars. For
example, epithelial stem cells
26
or satellite cells, the canonical muscle stem
cells,
27
are exposed to a 2D basal lamina, while HSC in the bone marrow appear
to be embedded in a 3D matrix.
16,28
The ECM provides cell adhesion and controls
cell shape, cell motility, such as during homing of stem cells back to the
niche,
29,30,31
but also stem cell maintenance
32,33
. The list of ECM components
that has been associated with adult stem cell regulation is extensive. Important
examples include osteopontin
34,35
, fibronectin
36
or the glycosaminoglycan
hyaluronic acid
37
which all have been described to play a role in HSC regulation.
Apart from adhesive functions, integrins can also control the cell cycle, and are
involved in signal transduction to regulate stem cell maintenance or
differentiation.
32,33
1.4.
Stem cell interaction with soluble niche signals
Many soluble signals such as growth factors have been described to play a role in
regulating adult stem cells. One class of molecules, the developmental
morphogen proteins, have been identified to play a role in many niches across
different species. For example, HSC maintenance seems to be controlled by
several of these proteins including Wnt-3a
38,39
, Sonic hedgehog (Shh)
40,41
, c-kit
ligand
42
, or FGF-1
43
. However, many proteins that are often studied in vitro in a
soluble form may not actually be soluble in vivo, but rather bound to the ECM
via intermolecular interactions such as electrostatic interactions. Heparin, a
heparan sulfate proteoglycan, can bind many morphogens with high affinitiy,
localizing their response to the niche and possibly protecting them from rapid
proteolytic inactivation.
44
1.5.
Stem cell functions controlled by the niche
An understanding of the dynamic behavior of individual stem cells and their
responsiveness to niche signals may be the key to the understanding of processes
that occur at the tissue level. Excluding death, we can distinguish between four
main single cell fate changes
(Fig. 2)
:
(i)
a stem cell never divides
(
quiescence;
Fig. 2a)
,
(ii)
a stem cell undergoes self-renewal divisions that result in one
daughter stem cell and one differentiated cell (termed
asymmetric
divisions -
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