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Stem cell therapy for arthritis

Oswestry is one of the few specialist Orthopaedic hospitals in the NHS which has a combination of scientists and surgeons able to develop new technologies into clinical care. Only cells can make tissues and this is the focus of our new developments. Teamwork has been essential to bring us to this point. A charity, the Institute of Orthopaedics at Oswestry, enabled our OsCell laboratory facility to be designed and built by Dr Brian Ashton and Principal Clinical Scientist Paul Harrison. Keele University Institute of Engineering and Science in Medicine supports the researchers, management at the Trust ensures cost-effective management of a clinical cell therapy service, our physiotherapists have developed the best post-operative rehabilitation, PCTs across the country have supported funding for their patients and all staff at the Robert Jones and Agnes Hunt hospital have enabled this development over many years.Patients are not just the reason for this development but have been volunteering to take part themselves in the clinical trials that are necessary in the development of new techniques. The MRC has funded us to lead the largest clinical randomised trial of cartilage cell implantation (ACI) in a network of hospitals across the UK and Norway, the trial compares chondrocytes against the best alternative surgical choices for the treatment of chondral defects. These defects result from injury or from subchondral bone thickening which is one of the ways arthritis develops. Using cells to treat these defects is a more "biological approach" than other options of treatment. Unfortunately the technique still does not work in 20% of patients. Professor Sally Roberts leads a team of scientists at the research department in Oswestry. She explains that "We are using the body's own cells to repair damaged joints. The hope is that it will be permanent and long-term repair". Studies by Dr Jan Herman Kuiper find that the improvement in symptoms at 15 months after ACI are maintained consistently over 9 years whereas the normal pattern without treatment is for symptoms to gradually become worse. Our aim now is to see if one type of cell can give a better result than another type of cell. A third possibility is that a combination of cells is even better, and there is some laboratory evidence to support this third option. If this can be proven in a study then it will lead the way to treating larger cartilage defects. We are not at the stage of recommending routine treatment for established arthritis where a knee replacement is indicated. Knee replacement is very effective in the older patient, where is will last in most people for over 20 years. Surgeons don't want to put implants into young patients in their 30s as the knee replacement will fail and need revision in the lifetime of the patient, perhaps on two or three occasions. This is the reason we are selecting younger people for the randomised trial.

Stem cells certainly have huge potential and often act as supporting cells for other cells. This is why the combination of stem cells and chondrocytes may be particularly useful. Arthritis Research UK, has been very supportive in providing funds to support analysis of our data from patients treated over the last 12 years. They will also be meeting the research costs of this study, which will be within the guidelines of NICE. These guidelines advise that Autologous cell therapy must be used for chondral defects that have failed other treatments. These trials should be preferably randomised and include an analysis of the cost-effectiveness of these treatments. Each year around 40,000 knee replacements are carried out in the UK, almost all of them due to osteoarthritis. The disease accounts for most of the estimated £5.7 billion a year economic cost to Britain of muscular and skeletal conditions. If a cell therapy can delay the need for a first joint replacement, then it will reduce the need of a revision surgery in later life. These are very costly to the NHS and a considerable undertaking for the then elderly patient. Compared to the cost of a knee revision in later life, treatment with a cell therapy is relatively inexpensive. The NHS needs to become more efficient and have long term views, and to develop new and better treatments. The trial is called ASCOT and the next step is to obtain ethics committee approval. Questionnaires of members of the public from across Europe have shown us that most people are very supportive of this type of development, particularly if the patient is using their own cells. Up to 100 people with chondral defects in the knee causing pain and tenderness will take part in the study, due to be launched at the Robert Jones and Agnes Hunt Orthopaedic Hospital in Oswestry, Shropshire, before the end of this year. In the trial, one group of patients will have stem cells. These will be removed from the bone marrow using keyhole surgery and grown in the laboratory for three weeks. They will then be implanted at open operation into the cartilage defect of the knee, and kept in place with a patch of collagen membrane called Chondrogide.

In a second group of patients, keyhole surgery of the knee will remove a small piece of healthy cartilage. In the laboratory the chondrocytes are separated and grown into 5 to 8 million cells over three weeks. Then they will be similarly implanted into the knee. A third group will have cells of both stem type and chondrocytes inserted behind the collagen patch. This group will therefore have twice as many cells as the other two groups. In order to have a comparison with the same number of cells as groups one and two, a fourth group will have half the number of stem cells, and half the number of chondrocytes inserted. This will also allow a comparison of the best dose of cells for treatment.

Allocation for treatment by one of these four methods will be chosen independently by the Oswestry Outcome Centre. Questionnaires, Histology and MRI are proposed as the best outcome measures to compare the different cell treatments. There has not been to our knowledge a trial comparing different cell treatments. This is our current plan, although we may be advised by the Ethics Committee to modify these plans. It is hoped that the combination of cells will trigger a type of mending so powerful that it could reduce the need for surgery and pain relieving drugs. Tests of the type of tissue formed as well as patients symptoms will help to decide which treatment group is giving the best results. We will also analyse a range of variables to study and help improve the outcome of cell therapies. We are optimistic that the procedure could produce robust new cartilage cells to treat patients with chondral defects. A combination of cells will mean increased work for our OsCell laboratory but offers real hope for people suffering with this early arthritis of the knee. When someone is young and otherwise fit, that person becomes very frustrated with their situation. The strength of the heart is affected, high blood pressure develops, and people put on extra weight as they are not active. All these things reduce the quality of life and so we hope we can find better treatments. It may be some time before we can offer this new trial as an option to patients. The Active trial continues to recruit until the end of August and there are centres across the country to give patients advice. Please see www.active-trial.org .uk. If you want to hear how our plans develop then I suggest you enrol with the newsletter on this site.

» more information about the procedures done at Oswestry Hospital
» more information about Stem Cell treatments
» more information about Autologous Chondrocyte Implantation
Click here to contact us regarding trials and work done by the OsCell team at the Oswestry Hospital.

BBC Interview with Professor James Richardson

The treatment will only be effective for patients in their 30s and 40s, not for older patients where new cells find it harder to regenerate. Professor James Richardson explains how the trial works in the video below from the BBC Interview.

Source: BBC News - Interview with Professor James Richardson at Oswestry Hospital

It’s great that Arthritis Research UK is funding this work in Oswestry to take things further. We are the first laboratory in the UK producing mesenchymal stem cells and chondrocytes for treating patients, so we are unique in being able to test the effectiveness of both types of cell therapy.