Biomedical Engineering Reference
In-Depth Information
transduction pathways and factors that positively and negatively control these
processes remain elusive and have not been studied systematically.
Once formed, the neural tube undergoes specification/patterning along the
rostro-caudal and dorso-ventral axis in the developing embryo. Neural patterning
is guided by secreted morphogens that form gradients across the neural tissue
thereby inducing specific transcription factors and neural phenotypes. The
principles of neural patterning using human pluripotent cell lines are based on
knowledge accumulated on animal models and require validation using human
cells [
27
]. The potency of morphogenetic factors such sonic hedgehog (SHH),
fibroblast growth factor 8 (FGF8), and retinoic acid (RA) has been confirmed in
the context of human neural precursors. However, because of the large variability
of published neural patterning protocols, it is important to strive for a more
standardized approach for the use of morphogenetic factors (i.e. effective
concentrations, treatment duration, appropriate developmental stage). Replacing
recombinant proteins by small molecules is highly desirable with regard to
standardization and large-scale applications and should be the main goal in all
stages of neural differentiation including terminal synaptic differentiation. Robust
and reproducible differentiation protocols will ensure the generation of pure
populations of specific neuronal, astroglial, and oligodendroglial cells. It should be
emphasized that the reproducible generation of astroglia and oligodendroglia from
pluripotent cells is particularly challenging and the molecular pathways involved
are poorly understood [
35
]. For instance, a recent study suggested that prolonged
cultivation of up to 180 days is necessary to produce immature astrocytic cells
from pluripotent cells [
36
].
1.4 Biomaterials and Disease Modeling
Stem cells in developing and adult organisms are thought to reside in highly
specialized niches, which directly affect their survival, regulation, and physiolog-
ical function [
37
]. This complex 3-dimensional microenvironment is defined by
signals mediated by cell-cell contact as well as diffusible factors. There is
increasing awareness that ordinary in vitro cell culture conditions fall short in
providing the appropriate physico-chemical context for stem cell growth and
differentiation. In fact, stem cell-based therapeutics including cell replacement,
tissue engineering, and organogenesis may require the exploitation of versatile
biomaterials. Hence, a more integrative approach that combines stem cell biology
with other disciplines such as bioengineering will leverage effective cell-based
therapies [
38
]. The realization of the importance of the stem cell niche has already
spurred the design and application of biomaterials and experimental platforms in
order to model specific aspects of the in vivo environment in high throughput [
39
].
The combined use of biodegradable matrices and cytokines presented to developing
cells as spatially arranged gradients is likely to play important roles in tailoring
personalized therapies. Similarly, to repair large parenchymal cavities after cystic
