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

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.

Advances in microfluidic in vitro systems for neurological disease modeling

“…The vast majority of microfluidic laboratories experimenting with new possibilities through rapid prototyping use PDMS due to its ease of fabrication, low cost production, optical clarity, gas permeability, and relative biocompatibility. PDMS is also used for its high elasticity, as in the Emulate Chip which enables stretch to be used to mimic breathing cycles (Huh, 2015) and vascular stretch (Sato et al, 2019). PDMS is, however, highly hydrophobic with a low surface energy that, unless treated, resists biological coatings and may also absorb small molecules such as drugs, which can have significant impacts on detection of analytes and drug bioavailability (van Meer et al, 2017).…”

3D-Printable Cell Crowding Device Enables Imaging of Live Cells in Compression

“…Unfortunately, there are limited experimental tools to enable such studies. Several commercial cell-stretching systems are available (e.g., from Flexcell International, NC, USA; Strex, CA, USA; CellScale, Ontario, Canada) and a number of custom-built devices using extensible silicone [7][8][9][10][11][12], piezoelectric [13], pneumatic [14][15][16][17] and recently dielectric actuation [18] have been reported. However, microscopy studies of crowding-induced live-cell extrusion are particularly demanding: cells must be cultured on stretched membranes for hours to days to reach confluency before crowding is induced and then must be imaged at high spatiotemporal resolution to observe their morphology and dynamics.…”

The ins and outs of engineering functional tissues and organs: evaluating the in-vitro and in-situ processes

“…Smart designs of bioreactors will allow decoupling of such cue combinations and help bridge our fundamental understanding of cell response (typically to single cues) and physiological tissue functions. For example, recent development of bioreactors that allow decoupling of mechanical stretch and shear flow demonstrates that these cues act nonsynergistically in regulating cell-cell signaling [70], cell proliferation [71], and neovessel formation [72], highlighting the need to better understand the underlying mechanisms of tissue growth. Second, bioreactors endow us with the possibility of quantitatively controlling the cues in a spatiotemporally resolved manner.…”