The osteogenic differentiation of mesenchymal stem cells by controlled cell-cell interaction on micropatterned surfaces.

Cell-cell interaction plays an important role in the control of cell functions. The precise control of cell-cell interaction will provide a useful tool to elucidate its influence on stem cell differentiation. In this study, four types of micropatterned surfaces were prepared by ultraviolet photolithography to investigate the effect of cell-cell interaction on the osteogenic differentiation of human mesenchymal stem cells (MSCs). Single MSCs adhered on the micropatterned surfaces following the micropatterns. Single cells on the isolated, barbell, linear, and honeycomb dot micropatterns had zero, one, two, and three cell-cell interaction partners, respectively. The number of cell-cell interaction of single MSCs was controlled by the different micropatterns, which showed evident effects on actin filament structure assembly and osteogenic differentiation of MSCs. MSCs with two and three interaction partners showed a significantly higher rate of osteogenic differentiation than did isolated single cells and cells with only one interaction partner. Thus, the osteogenic differentiation of MSCs was enhanced with increased cell-cell interaction. These results highlight the importance of cell-cell interaction in stem cell differentiation.