Role of Mechanical Stimulations in Directing Mesenchymal Stem Cell Adipogenesis - The Mechanobiology of Obesity and Related Diseases - page 76

Fig. 6 Patterned cell size affects MSC fate decision toward adipogenesis and osteogenesis.
a MSCs patterned within small area FN island showed adipogenesis (lipid staining in red). MSCs
patterned to spread out on large FN showed osteogenesis (alkaline phosphatase staining in blue).
b For cells patterned within small island, upregulation of RhoA by constitutively active RhoA-
V14 could not restore MSC osteogenesis. c Activating ROCK via constitutively active ROCKD3
rescued MSC osteogenesis even on small island. Reprinted with permission from Elsevier [ 33 ]
constrained within small pattern (Fig. 6 c). These strongly suggest mechanical
signals from the substrate cue, even though it is 'static', can significantly affect
cytoskeletal signaling and MSC fate decision.
A recent study by Song et al. [ 49 ] reported data on the cell patterning shape
effect on the MSC adipogenesis. Their approach was systematic in that the effect
of cell patterning shape (triangle, square, pentagon, hexagon, and circle) was tested
under a constant cell patterning size. Interestingly, the level of adipogenic dif-
ferentiation did not show different degree depending on the patterning shape. This
result, in comparison with the data on the cell patterning size effect as described
above, suggests that cell shape may be less influential in determining MSC adi-
pogenic fate than cell patterning size. Kilian et al. [ 21 ] also tested the effects of
cell patterning shape at the same cell area. The results, on the other hand, sug-
gested that cell shape affects the MSC fate decision. They observed differential
trends of MSC adipogenic and osteogenic differentiation profiles for rectangular
shapes with increasing aspect ratio and pentagonal shapes with different subcel-
lular curvature (Fig. 7 ). Furthermore, microarray analysis revealed that increased
MSC osteogenesis on specific cell patterns matched with the expressions of c-Jun
N-terminal kinase (JNK), ERK1/2, and Wnt signaling. It was also shown small
circular cell morphology produced by micropatterning could induce stem cell
adipogenesis [ 26 ].