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

促炎间充质干细胞在类风湿性关节炎中的作用

• 批准号: MR/K008862/1
• 负责人: Ilaria Bellantuono
• 金额: $ 5.33万
• 依托单位: University of Sheffield
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FK008862%2F1
• 关键词: role; pro; inflammatory; mesenchymal; stem

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.

类风湿性关节炎（RA）是一种常见的关节炎，大约每100人中就有1人在其生命的某个阶段受到影响。类风湿关节炎会引起关节发炎、疼痛和肿胀。这是一种持续的疾病，随着时间的推移会损害受影响的关节，严重程度从轻微到严重。类风湿性关节炎无法治愈，但治疗可以减轻症状。治疗方法包括治疗疾病的药物来抑制炎症。它们通常需要无限期服用，并且可能有副作用。如果疾病治疗药物不起作用，可以选择生物药物，如抗肿瘤坏死因子，它可以阻断炎症反应。生物药物的问题包括需要注射，而且价格昂贵。因此，只有在患者对其他治疗至少6个月没有反应的情况下才给予这种药物，在此期间，关节可能受到严重损害。因此需要新的治疗方法。最近，一种涉及干细胞移植的新疗法被提出作为治疗类风湿性关节炎的方法。这种干细胞被称为间充质干细胞（MSC），被认为能够永久地停止炎症。它们取自患者或健康志愿者的骨髓，在实验室进行治疗，并给予患者以停止炎症。到目前为止，这种方法偶尔有效，但不是对所有患者都有效，也不是无限期有效。当在类风湿性关节炎的动物模型中测试该方法时，也看到了同样的结果。在这里，我们想了解为什么会这样，并确定我们是否可以改进这个过程，以永久地停止炎症和治愈类风湿性关节炎。最近，科学家们发现有两种间充质干细胞，一种会增加炎症，称为MSC1，另一种会阻止炎症，称为MSC2。我们想测试RA患者的MSC1干细胞数量是否大于MSC2，以及对当前治疗无反应的患者的MSC1数量是否大于MSC2。我们还想测试我们是否能找到方法在实验室中治疗MSC1细胞，并使它们变成MSC2细胞，这样当给病人注射MSC2细胞时，炎症就能停止。我们想在动物身上验证这一假设，并在RA患者身上验证我们的一些发现。这将使我们想到新的方法，使干细胞移植在RA患者中更有效。