Biomedical Engineering Reference
In-Depth Information
There are developmental circumstances in which Wnt signaling is linked to
high Notch signaling and vice versa, showing clear antagonism. In other
circumstances, such as during somitogenesis, where the central pattern gen-
erator of development is the Notch-driven spatiotemporal cycles of gene
expression, it has been possible to identify the regulatory motif in which
Delta expression is under the control of Wnt signaling transduction (Aulehla
et al., 2003; Aulehla and Herrmann, 2004; Galceran et al., 2004; Pourquie,
2003). When the results of these studies are considered together, one may
conclude that the Wnt and Notch signaling pathways have an interactive
relationship during development.
3 The Stem Cell Niche
Stem cells are acquiring significant importance as valuable research tools and as
a potential resource for new cell substitution therapies for benign andmalignant
illnesses. Research has shown that the specific microenvironment in which stem
cells dwell is essential for their adequate function. As such, we need to explore
the concept of stem cell microenvironments and how they provide a platform
for developmental pathways and stem cells to interact, affecting their ultimate
cellular fate. A revolution in the field of stem cells occurred in 1998 when
Thomson et al. isolated human embryonic stem cells (hESCs). Many specula-
tive reports on somatic stem cell plasticity promoted the revolution ironically
paving the basis for regenerative medicine. In biological terms, the concept of a
microenvironment or niche in a solely architectural or geographical sense is
insufficient; a biological niche must also exert a functional sustaining role as
well as an anatomical dimension that facilitates resident stem cells to self-renew.
Studies have demonstrated that somatic stem cells have limited function outside
their microenvironment. Good examples of this are hematopoietic stem cells,
which have the power to regenerate successfully the entire blood and immune
system. However, these cells have little function outside specific cellular niches
where specific signals push them to follow physiologically appropriate fates.
Comprehending how the niche modulates stem cells will hopefully provide the
appropriate tools to therapeutically manipulate stem cells allowing new ways to
treat malformative, degenerative, and cancerous pathologies. We will now
bring to light some of the most relevant aspects of stem cell niches and the
evidence behind their importance.
3.1 Niche Infrastructure: The Extracellular Matrix
Studies in Drosophila and C. elegans have shown that germ stem cells in these
organisms localize at the distal end of a tapered structure. These stem cells
communicate with somatic cells that help them maintain their 'stemness'
