1. Understanding regenerative treatment by the study of patient samples
Since both surgeons and scientists are involved in this project, we can learn from patients who are being treated in hospitals in Oswestry and Cambridge. No treatment is ever perfect, and some patients will always do better than others. We can learn a lot by comparing those patients who do well and those patients who don’t do so well. If patients are happy for us to take samples of their blood or joint fluid (or even pieces of the ‘repaired’ cartilage) we can learn even more about the repair process and when they work best. This helps us improve the cell therapy treatments we have available, such as ASCOT in Oswestry.
2. Understanding human clinical trials
This work programme focuses on treatments for early arthritis in humans. The studies use cells from a patient, which are then grown in a laboratory. We then have a higher number of cells to return to the affected area of that patient. We use cells from cartilage, called chondrocytes, and stem cells from bone marrow and fat. This type of clinical study gives us the opportunity to collect the results from each new treatment, such as ACI (autologous chondrocyte implantation); a treatment that has been accepted within NICE Guidance. The studies not only allow us to improve on the treatments we provide but they also give us a lot of information so that we can gain a better understanding of osteoarthritis.
3. Finding the best cell types for therapy treatments
Cell therapy works by repairing or regenerating a damaged part of the body, in the hope that the part will be ‘good as new’ and never wear out. There are many different cells that could be used for this, such as cells from cartilage (chondrocytes), and stem cells from bone marrow and fat. Some cells may come from the patient themselves (autologous), from someone completely different (allogeneic) or even from an animal. With so many different types of cell to choose from we look to see if there are specific ‘markers’ on the cells. We can then find out which type of cell is better than another for healing.
4. Understanding the best cell and sub-populations in the laboratory
Not all stem cells are the same. We have discovered a new marker on some stem cells (CD317) that helps us sort out which cells are capable or not capable of producing new bone or cartilage. We then test these cells on mice and observe where the cells go after they have been transplanted into a joint. By doing this, we can find out whether the cells reduce swelling, how they interact with blood cells and whether they reveal to us new and simpler ways to treat osteoarthritis.
5. Tracking cells administered to a patient
This programme studies new methods of tracking the cells given to a patient and measuring how good they are in healing cartilage and bones in people with osteoarthritis. The study requires us to look at new ways of tracking cells by using methods that are already, or could easily be, available in the NHS. For example, we use small magnetic particles called SPIONS which show up on an MRI images and PET tracers. We are also investigating whether we can use new technologies associated with gene imaging.
6. Developing molecules to stimulate stem cells
Osteoarthritis causes breakdown of cartilage and bone, leading to joint failure. In this disease, stem cells in the joint fail to repair cartilage. An attractive treatment option is the development of drugs that modify the function of the stem cells to help them maintain healthy joints, and repair damaged ones. We have discovered that the membrane surrounding the cavity of joints such as the knee, which is called synovium, contains special stem cells. Our experiments show that in adult mice, these stem cells are able to repair joints after injury and we have identified a molecule (Yap) that plays a critical role in the function of stem cells. Our aim is to develop, through further research, novel drugs that help stem cells maintain healthy joints and prevent or even cure osteoarthritis at an early stage.
7. Developing treatments using cells
We have developed novel MRI methods to identify labelled stem cells inside joints. This technology enables us to track stem cells in joints in live animals and test the effects of treatment. We have also used a method of concentrating autologous cells (apheresis) to treat joint surface defects in sheep. These experiments have shown that the use of a treatment based on cells can significantly enhance healing 6 months after the injury.See also a more detailed overview