Science Spin July 2008 : Sponsored Content - REMEDI

Helping the body heal itself

The body is quite good with minor repairs, and many wounds, if clean, can be left to heal. However, when damage is severe or extensive, the natural repair systems are unable to cope, and the aim of researchers at REMEDI is to overcome these limitations. At REMEDI, the Regenerative Medicine Institute, scientists from a range of backgrounds have been looking at how gene and cell therapy can be used to enhance and promote natural repair processes. In some instances simply providing a supporting structure can give tissues a chance to grow back, and in many other cases topping up with adult stem cells has the potential to make up for serious deficiencies.

Tissues vary in their ability to recover, and we are all familiar with the speed at which most surface cuts heal. However, some tissues, such as cartilage, are much less responsive, and as Drs Cindy Coleman and Dr Elizabeth Hutson at REMEDI explained, this is one of the reasons why arthritis is such an enormous problem. Cartilage provides the cushion between all our moving joints, so we depend on it to keep moving. When cartilage deteriorates, we can end up so stiff and painful that joints have to be surgically replaced. In Ireland alone it is believed that one in six people is affected by arthritis, and with rising age, the number of patients for knee and hip replacement is set to rise.

In many cases failure of the cartilage tissue to repair itself leads on to osteoarthritis. The arthritis can be sparked off by a sports injury or by excessive weight bearing, and because the cartilage tissue is not good at self repair, the condition can gain the upper hand.

Different approaches are currently in place to deal with stiff and painful joints, such as injection of viscous lubricants, but as the researchers explained, these are just treatments to relieve symptoms and they are not a cure. To treat arthritis effectively, we have to have a better understanding of what's going on, and one of the main problems is that cartilage tissue is not vascular. Although it releases distress signals to fetch potentially reparative stem cells, it is poorly supplied with blood vessels, so the lines of communication to tap into sources of stem cells are extremely weak.

As the researchers explained, intervening to transfer stem cells could help to overcome that problem, and this is the focus of their CARA, Cellular Arthoplasty for Regeneration in Arthritis project. This project, put together by Dr Mary Murphy, senior researcher at REMEDI, is being run jointly with the global technology company, Smith & Nephew.

The project began when Smith & Nephew began looking at how to improve treatment of cartilage defects. This is a big market segment for the company, and as Elizabeth Hutson from Smith & Nephew remarked, the stem cell approach being taken by REMEDI was a perfect match for their own aims. The company, she said, has research facilities in York but, like many other multinationals, Smith & Nephew has an open innovation approach involving close collaboration with centres of international excellence. So, instead of trying to do eveything in house, long-term, in-depth research is undertaken in collaboration with specialised institutes that have complementary skills. Agreements like this are good for business and good for research, because both partners have a lot to gain. Companies end up with larger numbers of better products and the researchers benefit from a substantial boost in financial support. "REMEDI", she said, "was head hunted as one of the research groups that we wanted to work with."

The joint research deal was signed last year, and in the following months Sarah, Elizabeth and Nick moved over from the company to join the research team in Galway. They all brought considerable industry and research experience. Nick Medcalf, for example, started his career working on the analysis to support the development of one of the world's biggest selling drugs, Zantac, and he worked as a senior chemist during the start-up of a fine chemical company before moving on to work on scale up of processes for Smith & Nephew.

Cindy has a PhD from Thomas Jefferson University in development biology, and Elizabeth has a PhD in cell biology and tissue engineering of bone mesenchymal cells.Within four years the researchers plan to have made considerable progress on solving some extremely difficult problems, not least of which concerns more effective culturing of adult stem cells.

The stem cells are harvested from adult volunteer donors and while this provides enough for research purposes such samples would be completely inadequate for general use. For this reason one important aim of the research is to discover how to bulk up the supply. Although great progress has been made over the past few years, one of the problems that the researchers aim to overcome is that after dividing a few times in culture, cells start to grow old and lose their ability to proliferate. The researchers have been able to bulk up cultures to eight times their original volume, and as Dr Coleman said, the ultimate aim is to get the maximum yield from the minimum number of donors. However, as she added, "we need to know that they remain genetically the same, that they still have the same function."

The researchers are also looking at how these living cells can be introduced to the damaged site. With these mesenchymal stem cells there is unlikely to be any problem of rejection, and this is a major advantage. "They could be implanted or injected," Dr Coleman said, and by taking up residence, they act as an influence on the surrounding cells. "It is believed that the cells themselves don't do the repair, but it is thought that they help others to act, possibly by producing cytokines and growth factors which attract other cells to the site." Being in residence for a couple of weeks may be enough to stimulate self-repair.

Apart from Cindy, and the Smith & Nephew team members, Sarah, Elizabeth and Nick, the others involved on the €6 million project at REMEDI are post doc researcher, Caroline Ryan, and research assistant, Caroline Curtin. Close relations with the Merlin Park University Hospital are already helpful, and that collaboration is going to increase significantly as the project moves out from the lab and on into clinical trials.

According to Smith & Nephew over 100 million people around the world are suffering from osteoarthritis, and apart from being uncurable, the condition is progressive and painful. Smith & Nephew had already started to work on culturing human cartilage, but as the company's project manager, Nick Medcalf, commented, the agreement with REMEDI will accelerate this research. REMEDI, he said, are widely recognised as world leaders in this field.

Getting a regenerative treatment onto the market, could come as a great relief, particularly to younger patients, who often have to endure years on painkillers before hip or knee replacements.

REMEDI

The Regenerative Medicine Institute, REMEDI, was established in 2003 with Science Foundation Ireland support as a world class centre for gene therapy and stem cell research. REMEDI,located at the National Centre for Biomedical Engineering Science at NUI Galway benefits from close proximity to a range of related disciplines. Under directors Prof Timothy O'Brien and Prof Frank Barry, REMEDI has become recognised as one of the world's leading centres for stem cell research. Because stem cells, such as the mesenchymal cells taken from bone marrow, have not yet specialised, they retain a high degree of flexibility in how they will develop. It is this flexibility that gives stem cell therapy such high potential to cure rather than just treat certain diseases. Compared to whole tissue, stem cells are less likely to be rejected by the body's immune system and given the right conditions, they have the ability to grow and develop into any other type of fully functional specialised cells.