Biomedical Engineering Reference
In-Depth Information
In the following, the major components characterizing the SC microenvironment
are discussed to provide an overview of the subject, focusing on the SC niche of adult
SCs within the human body.
4.2.1 The SC Microenvironment or the SC Niche
Mechanical and Physicochemical Factors of the SC Microenvironment
The SC niche is the microenvironment which physically surrounds the SCs within
a given tissue and actively influences SC fate either to promote self-renewal and
the maintenance of the SC character or to promote the differentiation needed for
tissue repair or regeneration. Mechanical and physicochemical factors positively
or negatively regulate SC responses within the niche.
Mechanical triggers are derived from the ECM components, which form the
local structural geometry and topography. The elasticity of matrices constructed to
mimic the softness or rigidity of different tissues has been shown to directly
influence the differentiation of SCs into specific lineages in vitro [
170
-
172
]. The
mechanotransduction can also influence the SC shape via a physical control. This
effect seems to be activated by the adhesive interactions between the cell and its
substrate [
151
]. Cell shape, cytoskeletal tension, and the small GTPase RhoA
regulate SC lineage commitment [
173
]. Effects of the material on the cell response
are also dependent on the stage of cell commitment. It has been shown that more
differentiated cells are also more responsive to a model cell adhesion ligand [
174
].
Physicochemical factors such as pH, oxygen tension, and ionic strength also
regulate the fate of adult SCs. (see Fig.
5
for an overview). The pH is known to be
a modulator of cell proliferation. A reduced pH (7.1 instead of 7.6) increased the
cloning efficiency of progenitor cells and a pH between 7.2 and 7.4 was optimal for
their differentiation, at least in vitro [
175
]. Low oxygen concentration maintained
the cells in their undifferentiated and multipotent state [
176
]. The Ca
2+
content of
the niche seems to influence the favored localization of adult mammalian hema-
topoiesis in bone [
177
].
As well as the mechanical and physicochemical nature of the microenviron-
ment, cell-cell interactions between SCs, exchanges between SCs and neighboring
differentiated
cells,
and
interactions
between
SCs
and
adhesion
molecules
characterize the SC niche.
Cell-Cell and Cell-ECM Interactions
The interaction of SCs with their particular microenvironment is thought to be
responsible for SCs' fate, maintaining their potential and quiescent state and the
regulation of their specific differentiation properties. This is achieved next to the
solid-state signals (see
Sect. 4.2.1
) of cell-ECM interactions through a complex
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