ENGINEERING ARTIFICIAL STEM CELL NICHES - Biologically-Responsive Hybrid Biomaterials - page 281

a conventional cell culture substrate such as tissue culture plastic these cells often
undergo differentiation divisions due to the lack of instructive components from
the niche.
2. Engineering in vitro Surrogate Models of Stem Cell Niches
An emerging route towards overcoming the translational hurdles that stem cell
biology faces today involves the combination of stem cell biology with
biomolecular materials engineering and microfabrication technologies in order to
generate novel cell culture platforms that mimic crucial biochemical or structural
aspects of complex in vivo niches. Several lines of research towards such
'artificial niches' appear particularly promising and are briefly discussed below.
2.1. Engineering biomaterials with niche-like physicochemical
characteristics
Stem cell niches are soft and highly hydrated structures, rich in proteins and
sugars. Synthetic approaches that mimic these characteristics may be crucial in
controlling adult stem cell fate outside the niche. 56,57 A striking example of the
influence of matrix stiffness on stem cell fate was demonstrated by Engler and
colleagues. 58 Mesenchymal stem/progenitor cells were shown to alter their gene
expression patterns in response to the elasticity of a substrate, lending credence
to the notion that non-physiological rigid plastic surfaces could induce the
commitment of stem cells to undesired lineages. Modular hydrogel networks 59
formed from synthetic building blocks, should be a promising route to mimic the
physicochemical niche characteristics. Gel substrates are typically composed of
95-99% water and as a consequence are rather soft, with elastic moduli on the
order of hundreds of Pa to a few kPa. Moreover, many polymer hydrogels are
resistant to protein adsorption and cell adhesion. Biomolecular functionalization
can thus be conducted on an inert background, re-constructing complexity from
the 'bottom-up'.
Since many signaling cues in stem cell niches are presented in an
immobilized fashion, chemical schemes that permit the recapitulation of the
natural presentation mode of niche proteins have received increasing attention.
The well-controlled tethering of desired protein signals to a synthetic polymer is
not an easy obstacle to overcome, as non-specific crosslinking may compromise
the protein's bioactivity. Alberti and colleagues have presented interesting
approaches towards artificial niches with tethered protein cues whereby signaling