Could knee stem cells offer new hope on arthritis?
Tom Perks has been an enthusiastic football player ever since he could kick a ball. But from about the age of 14, one of his knees would regularly give way during a game. It progressively grew worse and, eventually, got so bad he had to give up the game he loved. Now aged 23, Perks has just taken part in a trial for a radical new technique in which patients with injuries to the cartilage in their knee joints are injected with new cartilage grown from their own stem cells. At the moment, it is available only to relatively young, otherwise fit people, whose knee joints have been damaged, usually from a sports injury or accident. However, the technique offers new hope of preventing the pain and disability of arthritis in later life as a result of knee damage. Tom Perks is one of increasing numbers of people in Britain who have undergone autologous chondrocyte implantation (ACI). It requires two operations, one to remove cartilage cells (chondrocytes), which are then grown in the laboratory. Three or four weeks later they are re-implanted in the damaged area, where they are held in place by a patch either taken from the membrane covering the shin bone or by a manufactured collagen patch. Articular cartilage is a tough, smooth, elastic tissue which covers the ends of bones that form joints. It enables the bones to move smoothly over one another and performs the vital function of a shock absorber, cushioning the bone from forces of more than five times the body's weight. Damaged articular cartilage in knees can cause the joint to be painful, swollen and difficult to move, restricting once-swift athletes to a hobble. A line-up of foot-ballers' knees is testament to how much damage contact sports can do to the delicate engineering of the knee joint. Unlike skin, cartilage does not have the ability to repair itself. Instead, the damage tends to spread, allowing the bones to rub against each other. Any repair tissue that does form is not like the original cartilage and doesn't work very well. Royal Alexandra Hospital in Paisley is conducting a trial of ACI along with 14 other hospitals in the UK and two in Norway. It is the only one in Scotland so far. Dr Heather Smith, the trial manager, based at the orthopaedic hospital in Oswestry, Shropshire, has so far recruited 60 patients for the trial as opposed to more traditional treatments. "We hope to have 600 patients eventually and there will be a long-term follow-up," she says. "We plan to analyse the results after five years and 10 years. The procedure was pioneered in Sweden in the mid-1990s by Lars Petersen, who treated Ole Gunnar Solskjaer, the injured Manchester United player, and is being used in the US and in Germany, with promising results so far. It is not available in this country on the NHS except as part of a trial." ACI is a more expensive technique, requiring two surgical procedures rather than one and therefore an increased risk as well as a longer rehabilitation period than other techniques. Dr Smith's trial is therefore part of an evaluation which will decide whether it should be available to NHS patients. Like Tom Perks, patients must have a very specific form of cartilage damage to take part in the trial. "You need stable knees – sometimes the cartilage we are trying to repair may be so damaged there is almost nothing to get hold of." Perks has no doubt the operation has been a success: "I had the operation at the end of August and my leg is now quite a lot better," he says. "It is still a bit swollen but I have no discomfort when walking, although I'm not up to a run. I have been back at work for four weeks. I am on my feet all day, because I repair roads and footpaths. "They look inside your knee with a camera to see how bad it is, then they make a couple of incisions to take out the cartilage. After four weeks the cells are grown and you have the second operation. For that, I was in hospital for three days. "I was attached to a machine which automatically bends and straightens your knee to keep everything moving. Then I went on to crutches and now I am walking normally. You have to keep up with the physio – it takes about two months for the leg to become weight-bearing and the rehabilitation programme continues for 12 months." To be eligible to take part, patients must have had a standard treatment which failed. There are several alternatives to ACI. The traditional one is debridement, which involves sucking or washing away loose and damaged pieces of cartilage via keyhole surgery. Abrasion or drilling takes this a step further until bleeding points are seen. The theory is that the underlying bone produces primitive blood cells which are then reformed into cartilage cells which cover the damaged area. Microfracture is a modification of the drilling technique. Debridement is carried out to form a stable perpendicular edge of healthy cartilage. Then multiple holes are made in the defect. Blood from the defect is washed away until a clot forms. This "super clot" is believed to be the optimal environment for tissue to regenerate within the lesion. The questions with these techniques, says Dr Smith, are whether the right type of cells are released, whether there are enough of them and whether they stay in the right place, whereas ACI is possibly a more accurate way of achieving regeneration of the cartilage. The great hope for ACI is that it results in permanent improvement. Patients for whom other treatments have failed, have only the alternative of a knee replacement, but these do not last for more than 15 years, so are not a good option for younger people. So far, ACI patients have reported continued improvements for up to two years, suggesting the transplanted cells may continue to form new cartilage for that length of time. It gives great hope to Tom Perks. He has been told to avoid contact sports for a while, but he hopes he might soon be able to have a kickabout with his five-year-old son and get back to the game he adores. "It would be great to get back on the pitch with the lads," he says.