title: A Novel Chip for Cyclic Stretch and Intermittent Hypoxia Cell Exposures Mimicking Obstructive Sleep Apnea.
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.
authors.affiliation: 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.
authors.forename: Noelia
authors.initials: N
authors.lastname: Campillo
authors.affiliation: 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.
authors.forename: Ignasi
authors.initials: I
authors.lastname: Jorba
authors.affiliation: Unitat de Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de BarcelonaBarcelona, Spain; Cellular and Respiratory Biomechanics, Institute for Bioengineering of CataloniaBarcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Schaedel
authors.affiliation: Unitat de Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de BarcelonaBarcelona, Spain; Cellular and Respiratory Biomechanics, Institute for Bioengineering of CataloniaBarcelona, Spain.
authors.forename: Blai
authors.initials: B
authors.lastname: Casals
authors.affiliation: Biological Sciences Division, Department of Pediatrics, Pritzker School of Medicine, The University of Chicago Chicago, IL, USA.
authors.forename: David
authors.initials: D
authors.lastname: Gozal
authors.affiliation: 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.
authors.forename: Ramon
authors.initials: R
authors.lastname: Farré
authors.affiliation: 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.
authors.forename: Isaac
authors.initials: I
authors.lastname: Almendros
authors.affiliation: 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.
authors.forename: Daniel
authors.initials: D
authors.lastname: Navajas
keywords: cell stretch; hypoxia-inducible factor; intermittent hypoxia; lab-on-a-chip; obstructive sleep apnea