FRONTIERS – Scientific Paper – Intermittent Hypoxia

Authors: Noelia Campillo, Ignasi Jorba, Laura Schaedel, Blai Casals, David Gozal, Ramon Farré, Isaac Almendros and Daniel Navajas.

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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 the main contributors to end-organ dysfunction in OSA patients and animal models. Since the molecular mechanisms underlying these in vivo pathological responses remain poorly understood, the 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 with 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.