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Front Physiol. 2016 Jul 29;7:319. doi: 10.3389/fphys.2016.00319. eCollection 2016.

A Novel Chip for Cyclic Stretch and Intermittent Hypoxia Cell Exposures Mimicking Obstructive Sleep Apnea.

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1
Unitat de Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de BarcelonaBarcelona, Spain; Cellular and Respiratory Biomechanics, Institute for Bioengineering of CataloniaBarcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades RespiratoriasMadrid, Spain.
2
Unitat de Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de BarcelonaBarcelona, Spain; Cellular and Respiratory Biomechanics, Institute for Bioengineering of CataloniaBarcelona, Spain.
3
Biological Sciences Division, Department of Pediatrics, Pritzker School of Medicine, The University of Chicago Chicago, IL, USA.
4
Unitat de Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de BarcelonaBarcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades RespiratoriasMadrid, Spain; Institut d'Investigacions Biomèdiques August Pi i SunyerBarcelona, Spain.

Abstract

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 ~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 1α (HIF-1α) 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.

KEYWORDS:

cell stretch; hypoxia-inducible factor; intermittent hypoxia; lab-on-a-chip; obstructive sleep apnea

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