PMID- 27524971 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20160815 LR - 20200930 IS - 1664-042X (Print) IS - 1664-042X (Electronic) IS - 1664-042X (Linking) VI - 7 DP - 2016 TI - A Novel Chip for Cyclic Stretch and Intermittent Hypoxia Cell Exposures Mimicking Obstructive Sleep Apnea. PG - 319 LID - 10.3389/fphys.2016.00319 [doi] LID - 319 AB - 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 1alpha (HIF-1alpha) 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. FAU - Campillo, Noelia AU - Campillo N AD - Unitat de Biofisica i Bioenginyeria, Facultat de Medicina, Universitat de BarcelonaBarcelona, Spain; Cellular and Respiratory Biomechanics, Institute for Bioengineering of CataloniaBarcelona, Spain; Centro de Investigacion Biomedica en Red de Enfermedades RespiratoriasMadrid, Spain. FAU - Jorba, Ignasi AU - Jorba I AD - Unitat de Biofisica i Bioenginyeria, Facultat de Medicina, Universitat de BarcelonaBarcelona, Spain; Cellular and Respiratory Biomechanics, Institute for Bioengineering of CataloniaBarcelona, Spain; Centro de Investigacion Biomedica en Red de Enfermedades RespiratoriasMadrid, Spain. FAU - Schaedel, Laura AU - Schaedel L AD - Unitat de Biofisica i Bioenginyeria, Facultat de Medicina, Universitat de BarcelonaBarcelona, Spain; Cellular and Respiratory Biomechanics, Institute for Bioengineering of CataloniaBarcelona, Spain. FAU - Casals, Blai AU - Casals B AD - Unitat de Biofisica i Bioenginyeria, Facultat de Medicina, Universitat de BarcelonaBarcelona, Spain; Cellular and Respiratory Biomechanics, Institute for Bioengineering of CataloniaBarcelona, Spain. FAU - Gozal, David AU - Gozal D AD - Biological Sciences Division, Department of Pediatrics, Pritzker School of Medicine, The University of Chicago Chicago, IL, USA. FAU - Farre, Ramon AU - Farre R AD - Unitat de Biofisica i Bioenginyeria, Facultat de Medicina, Universitat de BarcelonaBarcelona, Spain; Centro de Investigacion Biomedica en Red de Enfermedades RespiratoriasMadrid, Spain; Institut d'Investigacions Biomediques August Pi i SunyerBarcelona, Spain. FAU - Almendros, Isaac AU - Almendros I AD - Unitat de Biofisica i Bioenginyeria, Facultat de Medicina, Universitat de BarcelonaBarcelona, Spain; Centro de Investigacion Biomedica en Red de Enfermedades RespiratoriasMadrid, Spain; Institut d'Investigacions Biomediques August Pi i SunyerBarcelona, Spain. FAU - Navajas, Daniel AU - Navajas D AD - Unitat de Biofisica i Bioenginyeria, Facultat de Medicina, Universitat de BarcelonaBarcelona, Spain; Cellular and Respiratory Biomechanics, Institute for Bioengineering of CataloniaBarcelona, Spain; Centro de Investigacion Biomedica en Red de Enfermedades RespiratoriasMadrid, Spain. LA - eng PT - Journal Article DEP - 20160729 PL - Switzerland TA - Front Physiol JT - Frontiers in physiology JID - 101549006 PMC - PMC4965455 OTO - NOTNLM OT - cell stretch OT - hypoxia-inducible factor OT - intermittent hypoxia OT - lab-on-a-chip OT - obstructive sleep apnea EDAT- 2016/08/16 06:00 MHDA- 2016/08/16 06:01 PMCR- 2016/07/29 CRDT- 2016/08/16 06:00 PHST- 2016/05/13 00:00 [received] PHST- 2016/07/13 00:00 [accepted] PHST- 2016/08/16 06:00 [entrez] PHST- 2016/08/16 06:00 [pubmed] PHST- 2016/08/16 06:01 [medline] PHST- 2016/07/29 00:00 [pmc-release] AID - 10.3389/fphys.2016.00319 [doi] PST - epublish SO - Front Physiol. 2016 Jul 29;7:319. doi: 10.3389/fphys.2016.00319. eCollection 2016.