Abstract
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.
Highlights
Pulmonary arterial hypertension (PAH) is a rare disease characterized by increased pulmonary artery pressure, leading to right heart failure and death [1]
While there are many reports investigating the effects of stretch on the same plane, there are few reports on the effects of circumferential stretch
The PDMS membrane was peeled from the Polymethyl methacrylate (PMMA) substrate, and membrane manufacturing yield was as high as 94%
Summary
Pulmonary arterial hypertension (PAH) is a rare disease characterized by increased pulmonary artery pressure, leading to right heart failure and death [1]. The blood vessel closure in PAH is caused by the abnormal proliferation of pulmonary artery smooth muscle cells (PASMCs), endothelial cells (ECs), and fibroblasts, its mechanism is unknown. We previously reported the first successful isolation of PASMCs from patients, and characterized the cells by immunostaining and quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) techniques [3,4,5]. These cell-based experiments were performed under static culture conditions. Construction of a cell culture microenvironment that mimics the disease, using mechanical stress from fluid flow and stretching, is required to clarify the mechanism
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