細胞配列化と繰返引張刺激による血管平滑筋細胞の分化誘導への試み

抄録

Vascular smooth muscle cells (VSMCs), which align in the circumferential direction of the vascular wall, regulate vascular contraction and dilation. They actively remodel the vascular wall in which they reside through biochemical and biomechanical signals. However, mechanical environments in vivo are quite different from those of cultured cells: VSMCs in vivo show an elongated shape and form a tissue that aligns with the circumferential direction of the walls. In addition, it maintains its contractile capacity while continuously receiving tensile stimulation. Thus, in the present study, we used the micro-grooved PDMS substrate that mimics the elongated cell shapes and alignment observed in vivo. We found that VSMCs on the micro-grooved PDMS substrate changed elongated shape and their nuclear morphology to a slim shape similar to the nucleus of a cell in vivo which consequently improved SMC differentiation. Furthermore, we constructed an experimental method in which cyclic stretch stimulation is continuously applied in the direction of cell alignment, as in an actual arterial wall. The actin cytoskeleton except around the nucleus was reorganized obliquely to the direction of 10-60° from groove direction, although the cell body and the actin cytoskeleton around the nucleus maintained their orientation to the grooves. The results suggest that cell alignment and cyclic stretch stimulation can lead to more similar remodeling to F-actin in VSMCs in vivo.