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There are not many heart-lung transplant patients who have both the determination and the opportunity to tackle the disease that put them on the operating table. But after Julia Polak had her transplant she founded the Imperial College Tissue Engineering and Regenerative Medicine Centre in London. Today she is Professor Dame Julia Polak and has spent the 12 years since her operation researching ways to repair damaged lungs.
Polak was already involved in work on lung diseases when she became ill and discovered that she was suffering from pulmonary hypertension, a condition she had been investigating. The disease causes raised pressure in the blood vessels supplying the lungs, and can be life-threatening.
Her work today focuses on coaxing stem cells to replace diseased lung tissue. The first stage is to obtain the stem cells. This could be from an external source or a patient’s own cells (see panel right). Then the cells have to be primed to produce all the types of tissue needed in the lungs. Finally, they need to be delivered to the site of the damage by injection or direct application. Once in place, it is hoped that their natural ability to form new tissue will kick in and heal the damage.
Polak’s aim is to get so good at this that it will be possible to grow large quantities of stem cells in the lab, sufficient to have enough to hand for transplant into patients with lung disease.
This idea, using stem cells as self-activating repair kits, is perhaps the most well known of the potential benefits of stem-cell research. Many research groups across the country are learning how to manipulate these cells – teasing and nudging them into doing their bidding – and aiming to use them to treat myriad diseases.
By definition, stem cells have the ability to develop into many different types of tissue, and this poses a challenge. If you want to use them to treat, say, lung disease, it is no good if they produce bone tissue or heart muscle. Understanding just how they develop is the focus of Dr Lyle Armstrong, a senior lecturer in stem-cell biology at Newcastle University. Armstrong is looking at what causes stem cells to produce a particular cell type but he is also exploring how to take a differentiated cell, one already defined, and wind it backwards to its undifferentiated, undefined, state. If he succeeds, a sample of any tissue could be encouraged to produce any other cell type by running its programming backwards to produce stem cells, then forwards again to make the required tissue.
This has already been done with some cell types, called induced pluripotent stem cells, but they are unlikely to be suitable for use in patients.
Malcolm Alison, professor of stem-cell biology at Barts and the London School of Medicine and Dentistry, leads a group of researchers studying disease. While some of his work focuses on using stem cells to heal, he is also interested in what might be called the dark side of stem-cell biology. Many diseases, including cancers, fibrosis of the liver and some problems with transplanted organs, involve stem cells causing harm, growing the wrong tissue in the wrong place. If we can learn how to turn on stem cells then maybe we can turn them off, suggests Alison, potentially stopping cancers and other diseases in their tracks.
While these potential treatments are exciting, Robin Lovell-Badge, head of stem-cell biology and developmental genetics at the National Institute for Medical Research, believes that there is another, equally important, arm to stem-cell research. His work concentrates on using stem cells to understand some basic biology. Indeed, perhaps the biggest biological puzzle there is. How does a single ferti-lised egg produce hundreds of different types of tissue in an adult body? Stem cells can be used to study development in the test tube.
On top of that, Lovell-Badge says, stem cells might also help scientists to understand degenerative diseases. In these diseases the normal cell regeneration processes fail. As the science advances, stem cells could reproduce the disease in a test tube. For example, a small sample of skin from someone with motor neuron disease could be turned into stem cells in the test tube, and then encouraged to produce nerve cells. Researchers would then have cells that show the traits of motor neuron disease and could study them.
At present such work requires the use of imperfect animal models, or studying living patients. Lovell-Badge sees a future that will stop guinea pigs being used as human beings and human beings as guinea pigs.
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