22 June, 2015
By Dr Rameen Shakur
Sudden, vigorous exercise can cause a bit of a burn. We’ve all been there: chasing after a bus, a train, a dog or a personal best on the running track and we feel our chest tighten uncomfortably. This is hypoxia; it’s your heart telling you that its tissue is being starved of oxygen.
Patients with heart disease experience hypoxia regularly. With so little oxygen getting into the depths of the heart tissue, cells can die off, worsening a patient’s symptoms. Current clinical management by cardiologists like me has been to use drugs or interventions, such as stents in the arteries of heart. Now, chemists I am working with have discovered and used a new artificial substance that provides more oxygen for cells.
In this approach, developed at the University of Bristol, the oxygen-carrying protein myoglobin is attached to chemical components on the membrane of cells. The artificial membrane, known as a polymer-surfactant conjugate, provides a reservoir of oxygen that prevents hypoxia. My colleagues and I at the Wellcome Trust Sanger Institute and the Laboratory of Regenerative Medicine, University of Cambridge analysed the way this membrane affects stem cells and are now looking at how they effect heart muscle cells, and found that it might be able to change the way cells behave, without all the trouble of altering their genetic code.
Laboratory tests, where the membrane was applied to human stem cells shows very encouraging results. When genetic expression analysis was performed, researchers found significant down regulation (reduced activity) in the genes known to be responsible for causing hypoxia. This effect lasted in the cells for at least seven to 14 days.
The treatment is currently being tested on other cells and needs to be tested in live models before we can think about experimental clinical trials. There is a need for caution but there’s plenty of cause for optimism: this technique opens brand new research avenues in cardiology. The membrane may work in other tissues as well, presenting us with a whole new batch of possible therapeutic uses.
Innovation like this is impossible without collaboration. A team including chemists, stem cell biologists, genetic researchers and clinicians had to come together and share their expertise to get this idea off the ground. Let’s hope this continues and that we see more fresh eyes and fresh ideas transforming the way we treat heart conditions.
This is a real practical example of a successful translational project, taking basic science work and utilising it for the benefit of clinical medicine, to really have an impact on patient care and management. It is gratifying to work with so many dedicated scientists who share a common goal to improve the treatment options for patients with heart disease.
Rameen Shakur is a cardiologist at the Laboratory for Regenerative Medicine, Department of Surgery, School of Clinical Medicine, University of Cambridge, and a clinical researcher at the Wellcome Trust Sanger Institute.
- Armstrong JP, Shakur R, et al. (2015). Artificial membrane-binding proteins stimulate oxygenation of stem cells during engineering of large cartilage tissue. Nature Communications. DOI:10.1038/ncomms8405
- Laboratory for Regenerative Medicine, Department of Surgery, School of Clinical Medicine, University of Cambridge
- Bristol Centre for Functional Nanomaterials, University of Bristol
- Centre for Organized Matter Chemistry, University of Bristol
- School of Cellular and Molecular Medicine, University of Bristol