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Title:	A Novel chip for cyclic stretch and intermittent hypoxia cell exposures mimicking obstructive sleep apnea
Author:	Campillo, Noelia; Jorba, Ignasi; Schaedel, Laura; Casals, Blai; Gozal, David; Farré Ventura, Ramon; Almendros López, Isaac; Navajas Navarro, Daniel
Notes:	Intermittent hypoxia (IH), a hallmark of obstructive sleep apnea (OSA), plays a critical role in the pathogenesis of OSA-associated morbidities, especially in the cardiovascular and respiratory systems. Oxidative stress and inflammation induced by IH are suggested as main contributors of end-organ dysfunction in OSA patients and animal models. Since the molecular mechanisms underlying these in vivo pathological responses remain poorly understood, implementation of experimental in vitro cell-based systems capable of inducing high-frequency IH would be highly desirable. Here, we describe the design, fabrication, and validation of a versatile chip for subjecting cultured cells to fast changes in gas partial pressure and to cyclic stretch. The chip is fabricated with polydimethylsiloxane (PDMS) and consists of a cylindrical well-covered by a thin membrane. Cells cultured on top of the membrane can be subjected to fast changes in oxygen concentration (equilibrium time similar to 6 s). Moreover, cells can be subjected to cyclic stretch at cardiac or respiratory frequencies independently or simultaneously. Rat bone marrow-derived mesenchymal stem cells (MSCs) exposed to IH mimicking OSA and cyclic stretch at cardiac frequencies revealed that hypoxia-inducible factor 1 alpha (HIF-1 alpha) expression was increased in response to both stimuli. Thus, the chip provides a versatile tool for the study of cellular responses to cyclical hypoxia and stretch.
Subject(s):	-Síndromes d'apnea del son -Oxigen en l'organisme -Respiració -Sleep apnea syndromes -Oxygen in the body -Respiration
Rights:	cc-by (c) Campillo, Noelia et al., 2016 http://creativecommons.org/licenses/by/3.0/es
Document type:	Article Article - Published version
Published by:	Frontiers Media
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