Understanding cell behaviour to help treat major diseases
The ability to measure concentrations of oxygen inside living human cells is a key requirement to help advance our understanding and treatment of a range of serious medical conditions. These include ischaemic stroke (where the stroke is caused by a blockage in the artery, preventing sufficient oxygen from reaching the brain), neurodegenerative disorders, and cancer.
Current treatments for stroke, for example, are limited by our lack of understanding of how neuronal injury develops within the brain and why neurons survive or die after a stroke. The same issues lie behind the lack of a cure for most fatal and progressive neurodegenerative disorders. Similarly, understanding what causes cells to survive or die could be of major significance in developing more effective cancer treatments.
However, while there is a clear need for more sensitive and specific sensors and testing systems to understand the world of cellular bioenergetics, the reality is that very few satisfactory technologies have been developed to monitor oxygen levels within cells. It was for this reason that the European Union (EU)-funded OXY-SENSE project began in 2009. Set up as a four-year Marie Curie Industry-Academia Partnership and Pathways programme, OXY-SENSE brought together the Royal College of Surgeons in Ireland (RCSI) and the Ludwig-Maximilians University in Munich, together with two industrial partners, Siemens and Luxcel Biosciences, a company based in Cork, Ireland.
With Siemens providing expertise in software development and project management, and Luxcel providing new sensor materials designed for high-resolution detection of cellular oxygen, the project focused on biomedical research to better understand the role of cellular bioenergetics, and in particular mitochondria (the ‘power centres’ inside cells), in determining how cells respond to ischaemic injury, neurodegeneration and drug toxicity. Building on this research, and at the heart of the project, was the aim of creating safe and effective cellular oxygen imaging systems.
As OXY-SENSE’s project coordinator, Professor Jochen Prehn of the Royal College of Surgeons in Ireland, describes it, the project focused on extending the capabilities of probes developed by Luxcel. We wanted to demonstrate how we could use those probes to trace cellular oxygen by microscopy,” he explains. “What the OXY-SENSE project was all about was that we also wanted to measure oxygen concentration within respiring cells and tissues, in 3-D, continuously and in real time,” he adds.
Having successfully found a way to introduce the probes safely into the cell, and then to measure the oxygen there, the results were remarkable, says Professor Prehn. “We actually calibrated the oxygen concentration in the cells, so that you really can now get a quantitative analysis of oxygen concentrations in cells and how these change in response to various conditions.”
The probe has still to complete the in vivo testing phase, but if this is successful the OXY-SENSE project will have taken an important step towards enabling our understanding how and why cells die – and therefore to the development of more effective treatments for a number of medical conditions.
In bringing together academia and industry in a close working partnership, accelerating the technology transfer process and the commercial exploitation of research findings, the project will have also achieved another of its important goals, benefiting not just patients, but European competitiveness as a whole.