HypOxygen's Blog - Latest News from HypOxygen

World Heart Day

September 29, 2016 is World Heart Day, when organizations globally advocate “creating heart-healthy environments”, for example by eating more healthily and exercising 30 minutes a day. Healthy environments are also a priority for Don Whitley Scientific and HypOxygen, whose HypOxystation is used globally by cardiovascular researchers to mimic the in vivo environment, so cells behave in a physiologically relevant manner. Temperature, CO2, oxygen and humidity are controlled in the HypOxystation, and cells are cultured and manipulated in that physiological environment without ever experiencing the “oxygen shock” of the bench atmosphere. The in vivo environment recreated in the HypOxystation is healthy with regard to metabolism, proliferation, signaling, and drug responsiveness, to name a few.

Hear Dr. Michael Cross, Molecular and Clinical Pharmacology Department, University of Liverpool, speak about his work with cardiac spheroids to assess cardiovascular drug toxicity. “The H35 allows us to generate oxygen levels that reflect the in vivo physiology these cells would be exposed to. We chose the Hypoxystation with its oxygen profiling feature, which allows us to recreate cycles of ischemia, where oxygen levels typically sink to 1-3%”.

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HypOxystation Gas Consumption Studies

Patrick Frost, Professor at UCLA and the West Los Angeles Medical Center, investigates how targeting angiogenesis and the adaptive hypoxic response in multiple myeloma cells affects tumor progression. He hopes his studies will provide insight into the pathology and chemotherapy resistance of this incurable disease, which occurs with a significant frequency in the Veteran population. He has been using the H35 HypOxystation for almost 3 years now, and he does not miss bygone days in the lab: “We started out with just a Plexiglas box, with some valves in it, with a front cover just held on magnetically, placed inside an incubator. We would burn through a 50 L tank of nitrogen in 48 hours. I was never convinced that we had the correct level of oxygen in there”.

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HypOxystation and the TRACER Project

HypOxystation user Brad Wouters at the Princess Margaret Cancer Center in Toronto was a collaborator in a recent publication on “A three-dimensional engineered tumour for spatial snapshot analysis of cell metabolism and phenotype in hypoxic gradients“ (Rodenhizer et al., Nature Materials 15, 227–234, 2016). Dr. Wouters told HypOxygen that “we describe a new device that enables us to create naturally occurring oxygen gradients, such as the ones found in tumors. We use the HypOxystation to establish a baseline, as a control, on unrolled TRACER membranes …We can set the external concentration to a fixed oxygen level and look at the resulting gradients and metabolites and so on, too… The external level is what we define. That could be 20% oxygen, but it could also be 1% or 2%, and in that case we can have the rolled-up TRACER inside the hypoxia chamber. We have tried out various oxygen levels in the hypoxia workstation and the oxygen gradients in the TRACER are very different, as are the metabolite gradients.“

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Keystone Symposia "New Frontiers in Understanding Tumor Metabolism" in Banff

At this week’s Keystone Symposia “New Frontiers in Understanding Tumor Metabolism” joint with “Immunometabolism in Immune Function and Inflammatory Disease”, taking place in the dramatic mountain panorama of Banff National Park in Canada, almost 600 researchers have come together to present and discuss their newest data. Certainly, there is a common theme of metabolism to all these talks and posters, so rushing from one session to the other is very much the thing to do here. HypOxygen is at the conference (poster exhibit hall Q7) exhibiting the Don Whitley Scientific HypOxystation for low oxygen cell culture.

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IDH1 Mutated Cells Demonstrate Pseudohypoxic Proline Metabolism

This week at the Keystone Symposia “New Frontiers in Understanding Tumor Metabolism” joint with “Immunometabolism in Immune Function and Inflammatory Disease”, HypOxystation user Kate Hollinshead of the Institute of Metabolism and Systems Research at the University of Birmingham in the UK presented both a poster and held a talk on her results. Her project, carried out together with colleagues in La Jolla, California and Cambridge, UK, is entitled “IDH1 mutated cells demonstrate pseudohypoxic proline metabolism”. The lab currently utilizes two Don Whitley Scientific H35 HypOxystations for their low oxygen cell culture work.

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Are your cells holding their breath?

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The hypoxic microenvironment exerts a significant influence on the epigenetic regulation of stem cell fate and behavior in vivo, and the role of low oxygen in maintenance and differentiation of stem cells in culture is coming under intense scrutiny. Epigenetic responsiveness to environmental cues in the cell environment to optimize gene expression can be modulated through chromatin or histone modification, transcriptional co-regulators and methylation/demethylation sequences (Tsai & Wu, 2014). The pathways regulating stem cell behavior are particularly interesting in the light of regenerative therapies, and oxygen level has been shown by many groups to be a master determinant of both pluripotency and differentiation. Hypoxia can, for example, induce microRNA’s that target the 3’ untranslated region of histone deacetylases, driving embryonic stem cells to differentiate into the myogenic lineage (Lee et al, 2015). Transcriptional activation of anti-angiogenesis genes during hypoxia as mediated by epigenetic changes in methylation patterns influences the status of stem cell-like populations in tumors (Ueda et al., 2014).

Read more: Are your cells holding their breath?