Body building in bristol
18 November 2003
As the population ages, the concept of 'regenerative' medicine is becoming recognised as an important new approach to solving many of our long-term healthcare needs.
Bristol has a long tradition of engineering. Brunel led the way in the 19th century with his construction of such wonders as the Great Western Railway, the Clifton Suspension Bridge and the SS Great Britain. In the 20th century the aerospace industry literally took off in Bristol, with the design and construction of Concorde as its flagship. At the start of the 21st century we have a new engineering goal: the construction of tissues and organs. It is part of a new programme of regenerative medicine that will ultimately revolutionise healthcare.
The ageing population will present healthcare organisations with unprecedented demands
The aim of regenerative medicine is to restore normal function to organs and tissues that do not function properly as a result of disease, traumatic injury or birth defects. This can be achieved using a range of therapeutic approaches that primarily include stem cells, tissue engineering and gene therapy.
Our rapidly expanding knowledge of the cellular basis of disease, and the genes that might make individuals particularly susceptible, will give us ample opportunity to reverse the processes of tissue destruction. Since the world’s ageing population will increasingly present healthcare organisations with an unprecedented demand for solutions to the failure of tissues and organs late in life, the time is now right for regenerative medicine to be developed and exploited clinically and commercially.
In the three- to five-day-old embryo, a small group of about 30 cells ‘differentiate’ into the hundreds of highly specialised cells needed to make up an adult organism. However, a small number of undifferentiated ‘stem cells’ persist in some tissue, such as bone marrow. The human body has over 200 different kinds of these specialised cells that help maintain the function of the particular tissue or organ in which they are found, but in order for the body to function normally, these cells must be continuously replaced when they die. Stem cells, on the other hand, have the unique property of almost indefinite self-renewal. They are the Peter Pan of the cellular world, although they can be persuaded to ‘grow up’ if they are exposed to the right biological signals.
As we get older mature cells become less good at doing their job and are often rather poor at generating tissue. We can get around this problem by obtaining stem cells and giving them the right signals to grow into the particular kind of mature cell that we need.
Tissue cells grown from the cartilage in your nose could be implanted into your knee
To grow and use an engineered tissue you need to start with the best available cells, put them onto a scaffold material that will help to guide their growth, and then find a way of implanting the constructed tissue into the body. Mature cells taken from a tissue biopsy must be increased to a much larger number, seeded onto a scaffold material and grown in a bioreactor that provides gentle movement as the new tissue forms. This movement is essential to ensure that nourishment reaches the very centre of the growing tissue.
Gene therapy is the introduction of new genes into the body in place of faulty ones and is likely to be of most benefit for patients with inherited disorders resulting from a single gene. However, we can also put new genes into cells that are going to be used for tissue engineering. By using a genetic switching mechanism it is possible to turn on the gene while the tissue is growing in the laboratory and then switch it off before the engineered product is implanted into the body.
Osteoarthritis provides an excellent example of why regenerative medicine must become an essential therapeutic tool and how stem cells, tissue engineering and gene therapy will be used together. Osteoarthritis is predominantly an ageing disease. It develops when cartilage, the shockabsorbing protective tissue found wherever bone meets bone, becomes damaged and erodes away, and the underlying bone becomes thicker. By the time you are 65 there is a 50 per cent chance that you will have damage associated with osteoarthritis. This translates into almost eight million people in the UK with osteoarthritic joints, a million of which are severe enough to require specialist health care. Demographic changes suggest that these numbers will double over the next 20 years, presenting a huge challenge to the NHS in meeting an insatiable demand for hip and knee replacements.
Because cartilage is unusual in having only one single cell type – the chondrocyte – its relative simplicity makes it an ideal target for repair by tissue engineering. For younger people with injury-induced osteoarthritis it is already possible to take a biopsy of normal cartilage from a part of the knee which does not carry much weight and extract the chondrocytes for tissue engineering. In Bristol however, we are particularly interested in finding more effective cells for cartilage repair. We are therefore exploring the possibility that using cells from the cartilage in your nose could be an improved way to grow tissue that will be implanted into your knee.
But for older people with osteoarthritis the mature chondrocytes often do not function well enough for tissue engineering. For these patients, taking adult stem cells and turning them into fresh, young chondrocytes may be the best answer. Consequently, we are developing new ways of extracting the rare stem cells found in bone marrow and turning them into mature cells. We may need to use specifically designed drugs or introduce new genes to influence the way in which the stem cells grow in the laboratory.
Stem cells, gene therapy and tissue engineering, the three mainstays of regenerative medicine, will offer us the opportunity to help patients with all sorts of chronic disease that we once thought untreatable. Diabetes, multiplesclerosis and kidney disease are all potential targets. Our challenge now is to persuade industry and government to invest fully in this exciting area of research and to inform the public about our ideas so that they are not fearful of this brave new world, but embrace it with open arms.