Dynamic mechanical response in a human stem cell-derived smooth muscle cell model.

Vascular smooth muscle cells (vSMCs) maintain vascular tone and regulate the contraction of blood vessels under dynamic mechanical conditions. These cells have diverse roles and undergo switching between synthetic (proliferative) and contractile (mechanically active) phenotypes in response to developmental, environmental, or pathophysiological cues. We have developed a well-defined human induced pluripotent stem (hiPS) cell-derived vSMC model to determine the mechanical forces generated by these cells after phenotype switching and from vSMC generated from hiPS cells harboring a genetic mutation that leads to vascular Ehlers-Danlos Syndrome (vEDS). This disease can lead to arterial tears and premature death. vSMCs differentiated from this mutant hiPS cell line show increases in contractile proteins and increased contractile forces in both the synthetic and mechanically active phenotypes relative to isogenic controls. These functional differences suggest that mechanical abnormalities may contribute to the pathophysiology of vEDS. Assessments of mechanical and phenotypic responses of hiPS-vSMCs to external mechanical conditions that model the dynamic vascular environment, including applied cyclic stretch, will be discussed.