Artificial Scaffolds and Mesenchymal Stem Cells for Hard Tissues - Tissue Engineering: Cell-Surface Interactions for Tissue Culture - page 180

4.2.2 SCs on Artificial Surfaces Mimicking the SC Microenvironment
Cells, including SCs, seem to have a robust intrinsically determined set of cell
fates. They can be quiescent or proliferative, they can differentiate or die, but the
choices are very selective. Waddington's epigenetic landscape has been an
accepted model for this since 1956 [ 195 ]. It describes a landscape of valleys and
hills and a marble (the cell) which ultimately rolls downhill and the only choice is
through which valley, meaning which lineage-specific differentiation pathway or
other fate the cell can have. This model was greatly challenged when Yamanaka
introduced his iPS cells [ 27 ]. This would show cells rolling up-hill in Wadding-
ton's landscape, a reaction which was thought it be impossible. The question now
arises whether the model is wrong or whether it can be altered. An revised model
has been suggested by Huang and Ingber [ 196 ]. It reminds the authors of Einstein's
space-time bending where gravity effects are often pictured as dents in a layer and
the deepness of the dent is dependent on the size of the star or planet. This model
seems to be a good new representation of (stem) cell fate with the dents being
proliferation, differentiation or apoptosis. The lack of a down-hill feature as in the
Waddington model also allows the explanation of reprogramming processes as in
iPS, but the limited number of possible fates (number of dents) is preserved by this
picture, too. It also allows an explanation of the hotly discussed topic of whether a
SC can differentiate invitro into lineages which in nature would not be an expected
fate of this specific SC, a feature which is called transdifferentiation. This means
the differentiation of a SC which should be lineage-committed to the cells of a
specific germinal layer (ectoderm, endoderm or mesoderm), but can be differen-
tiated into one of the other two layers.
SCs' fate can be affected by ECM properties. Therefore an artificial surface
cannot only be used to systematically examine and reconstruct individual niche
components for a better understanding, as already discussed in the paragraph
above [ 194 ], it could also be altered to trigger the SCs into a fate which was not
planned for this SC in nature. There is increased scientific effort to use artificial
surfaces to influence the biological system [ 189 , 197 ]. One focus is the use of
bioactive native or artificial ligands which influence the fate of SCs bound or
loosely integrated into the matrix, because these factors are known to be key
players in the SC niche (see Sect. 4.2.1 ). Another focus of research to influence
SCs' fate on artificial scaffolds is the nanostructure of the surface [ 198 ]. It has been
shown that the surface structure directly influences the lineage-specific differen-
tiation of SCs, but the thinness of the matrix can also trigger the differentiation
process. The tension caused by size variations and physical deformation within the
matrix influencing cell shape and cell distortion seems to be a dominant control
element to guide cell fate. Naive MSCs have been shown to commit to phenotypes
with high sensitivity to tissue-level elasticity. Soft matrices mimicking brain are
neurogenic, stiffer matrices mimicking muscle are myogenic, and rather rigid
matrices mimicking collagenous bone have been proven to trigger the osteogenic
lineage commitment (see Fig. 5 )[ 170 ].