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A microfluidic cell stretch device was developed to investigate the effects of stretching stress on pulmonary artery smooth muscle cell (PASMC) proliferation in pulmonary arterial hypertension (PAH). The microfluidic device harbors upper cell culture and lower control channels, separated by a stretchable poly(dimethylsiloxane) membrane that acts as a cell culture substrate. The lower channel inlet was connected to a vacuum pump via a digital switch-controlled solenoid valve. For cyclic stretch at heartbeat frequency (80 bpm), the open or close time for each valve was set to 0.38 s. Proliferation of normal PASMCs and those obtained from patients was enhanced by the circumferential stretching stimulation. This is the first report showing patient cells increased in number by stretching stress. These results are consistent with the abnormal proliferation observed in PAH. Circumferential stretch stress was applied to the cells without increasing the pressure inside the microchannel. Our data may suggest that the stretch stress itself promotes cell proliferation in PAH.

inventions

A Microfluidic Cell Stretch Device to Investigate the Effects of Stretching Stress on Artery Smooth Muscle Cell Proliferation in Pulmonary Arterial Hypertension