Artificial Scaffolds and Mesenchymal Stem Cells for Hard Tissues - Tissue Engineering: Cell-Surface Interactions for Tissue Culture - page 178

Fig. 5 SCs and their natural microenvironment. SCs are affected by their microenvironment
which is defined by ECM properties such as elasticity and geometry, molecules which connect to
the ECM, for instance TGF-b, TIPs, integrins, and transient receptor potential (TRP) which can
regulate cytoskeleton tension, successively followed by gene expression and focal adhesion
though the activation of a series of mechanical transduction events. Various soluble factors such
as extracellular nucleotide, growth factors, and cytokines also influence SC fate. Mechanical
forces such as shear stress and blood pressure influence SC proliferation and differentiation from
the media side of the niche as well as chemical and physical factors like pH or oxygen
system of paracrine signals via growth factors and cytokines as well as through
autocrine neighboring cell-SC and SC-SC interactions.
A typical example of cell-ECM interactions is the action via the transmem-
brane adhesion receptor family of the integrins bound to insoluble ECM proteins.
However, the ligand-activated induction of these transmembrane receptors is not
the only effect of the integrins. There is also a structural component via tractional
forces, which leads to a rearrangement of the actin and thus a cell shape change,
which both together influence proliferation [ 178 ]. Other pathways with a similar
effect involve TGF-b, tension-induced proteins (TIPs), and non-muscle myosin, all
ultimately influencing SC shape and fate (see Fig. 5 for an overview) [ 179 , 180 ].
The soluble factors can be classified into those which act on a more general
basis and those which have a more specific effect, but both will ultimately
determine SC behavior. Several chemicals seem to be more universal differenti-
ation-inducing factors. A typical example is retinoic acid (RA), which can change
the differentiation status of the epidermis [ 181 ] and also induce differentiation in
neuronal and hematopoietic cells [ 182 , 183 ]. Another molecule group very broadly
affecting SCs is the purine derivatives. ATP itself is not only an energy source, it is