Rheumatoid arthritis (RA) is a common form of arthritis affecting about 1 in 100 people at some stage in their life. Rheumatoid arthritis causes inflammation, pain, and swelling of joints. It is a persistent disease and over time can damage affected joints with a severity from mild to severe. There is no cure for RA, but treatments can reduce symptoms. Treatments include disease-modifying medicines to suppress inflammation. They usually need to be taken indefinitely and may have side-effects. If disease modifying medicines do not work the alternative is biological medicine such as anti-TNF, which blocks the inflammatory response. Problem with biological medicines includes that they need to be given by injection and they are expensive. Therefore they are only given if a patient has not responded to other treatment for at least 6 months, during which time, the joint can be severely damaged. Therefore new treatments are required. Recently a new treatment involving transplantation of stem cells has been proposed as a cure for RA. The stem cells are called mesenchymal stem cells (MSC) and and are thought to be able to stop inflammation permanently. They are taken from the bone marrow of patients or healthy volunteers, treated in the laboratory and given to the patient to stop inflammation. So far this has worked on occasion but not in all patients and not indefinitely. The same results are seen when the procedure is tested in animal models of RA. Here we want to understand why that is and determine whether we can improve this procedure to permanently stop inflammation and cure RA. Recently scientists have discovered that there are two types of mesenchymal stem cells, ones that increase inflammation, called MSC1 and ones that stop it, called MSC2. We want to test whether with RA the number of MSC1 stem cells is greater than MSC2, and whether patients who are not responsive to current therapies have the greatest numbers of MSC1 compared to MSC2. We also want to test whether we can find ways to treat MSC1 cells in the laboratory and make them become MSC2 cells so that inflammation can be stopped when they are given to the patient. We want to test this hypothesis in animals and verify some of our findings in patients affected by RA. This will allow us to think of new ways to make transplantation of MSC in patients affected by RA more effective.