The role of pro-inflammatory mesenchymal stem cells in rheumatoid arthritis

风湿性关节炎（RA）是一种常见的关节炎，在其生命的某个阶段影响约1/100的人。风湿性关节炎会导致关节发炎、疼痛和肿胀。这是一种持续性疾病，随着时间的推移，会损害受影响的关节，严重程度从轻度到重度。RA没有治愈方法，但治疗可以减轻症状。治疗方法包括使用缓解疾病的药物来抑制炎症。它们通常需要无限期地服用，并且可能有副作用。如果疾病修饰药物不起作用，替代品是生物药物，如抗TNF，它可以阻断炎症反应。生物药物的问题包括它们需要通过注射给药，而且价格昂贵。因此，只有在患者对其他治疗至少6个月没有反应时才给予这些药物，在此期间，关节可能会严重受损。因此，需要新的治疗方法。最近，一种涉及干细胞移植的新治疗方法被提出来作为治疗RA的方法。这种干细胞被称为间充质干细胞（MSC），被认为能够永久阻止炎症。它们取自患者或健康志愿者的骨髓，在实验室中进行治疗，并给予患者以停止炎症。到目前为止，这种方法偶尔有效，但并非对所有患者都有效，也不是无限期有效。当在RA动物模型中测试该程序时，看到了相同的结果。在这里，我们想了解为什么会这样，并确定我们是否可以改善这种程序，以永久停止炎症和治愈RA。最近，科学家们发现，有两种类型的间充质干细胞，一种是增加炎症，称为MSC 1，另一种是停止炎症，称为MSC 2。我们想测试RA患者的MSC 1干细胞数量是否大于MSC 2，以及对目前治疗无反应的患者的MSC 1数量是否大于MSC 2。我们还想测试我们是否可以找到在实验室中处理MSC 1细胞的方法，并使它们成为MSC 2细胞，以便在给予患者时可以停止炎症。我们想在动物身上验证这个假设，并在类风湿关节炎患者身上验证我们的一些发现。这将使我们能够想到新的方法，使受RA影响的患者的MSC移植更有效。

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.