ENGINEERING ARTIFICIAL STEM CELL NICHES - Biologically-Responsive Hybrid Biomaterials - page 274

responsible for stem cell self-renewal and specialization, or the reversion of
somatic cells to an iPS state. As a result, we do not know how to grow stem cells
in culture once they are removed from their niche: most adult stem cell types
rapidly specialize upon extraction from their tissue, and it is still very
cumbersome to specialize in a well-controlled, directed manner pluripotent
embryonic stem or iPS cells into the many differentiated cell types of the body.
To shed light on the mechanisms that regulate stem cells, technologies that
allow us to study the function of an isolated component of the complex in vivo
regulatory system are crucial. Biomaterials are one such emerging area that is
poised to assist stem cell biology and move it one step closer to the clinic. The
prime driving force for the application of biomaterials in stem cell biology is the
possibility to fabricate matrices that recapitulate, nearly down to the molecular
details, the microenvironment, or niche, in which stem cells reside naturally.
Biomaterials could then, for example, be exploited as modular toolboxes to
construct de novo niches with diverse biochemical and biophysical properties,
enabling quantitative analyses of stem cell behavior in a manner previously not
possible. Furthermore, an integration of biomaterials technologies with
microfabrication platforms such as biomolecule micropatterning or microfluidics
could open up new avenues for identifying stem cell regulators and investigating
stem cell behavior at the single cell level and in high-throughput. Equally
exciting, knowledge gleaned from such studies could feed into efforts that aim to
reconstruct tissue-like multicellular constructs with applications in many areas of
Life Science. This chapter highlights, by way of selected examples, biomaterials
approaches to probe and manipulate stem cells, changing their fate in a
predictable manner.
1.1. Adult stem cells are regulated by niches
Adult stem cells are harbored in anatomically well-defined locations termed
niches. 3,4,5,6,7,8 Niches are composed of countless biomolecular signals that, in
concert with cell-intrinsic regulatory networks, regulate stem cell function. The
presence of the niche is crucial, as its absence often leads to the loss of stem cell
function, which in turn can have dramatic consequences for tissue function and
can completely impair regeneration. The niche concept was postulated first on
hematopoietic (blood) stem cells more than two decades ago by Schofield, 9 but
concrete proof of the existence and function of niches was only provided ca. one
decade ago in seminal studies of stem cells in fruit flies (e.g.: 10,11,12,13 ). More
recently, niches have been identified and characterized in nearly all tissues of
mammals, including the skin (in the bulge region of the hair follicle), intestine