Bad stem cells: are they responsible for rheumatoid arthritis?

Disease - Rheumatoid arthritis

Lead applicant - Professor Cosimo De Bari

Organisation - University of Aberdeen

Type of grant - Project Grant

Status of grant - Active

Amount of the original award - £201,718.40

Start date - 1 November 2011

Reference - 19667

Public Summary

What are the aims of this research?

We intend to test the theory that RA is sustained and perpetuated by diseased stem cells in the joint that give rise to abnormal tissue which causes loss of bone and cartilage.

Why is this research important?

Over 400,000 people in the UK are affected by RA. It tends to strike during the most productive years and within ten years of onset around half of patients are unable to work. Current treatments for RA are not ideal as not all patients respond to treatment. Even when joint inflammation is under control joint damage can still progress. This suggests that the mechanisms of joint destruction are partly independent of inflammation. We need to understand these mechanisms more fully to develop new drugs that can also halt the progression of RA.

In RA, cells called synovial fibroblasts which are present in the synovial membrane of joints, increase dramatically in number to form pannus. This is a tumour-like tissue that causes joint damage, and spreads disease to unaffected joints. However, the origin and nature of the synovial fibroblasts, key cells in RA, remain unknown. Our recent work indicates that in healthy joints the synovial fibroblast is a type of stem cell. Stem cells are responsible for the maintenance and renewal of tissues throughout life. If “bad” stem cells lead to RA, then we can develop novel medications to target them to halt disease progression and to restore normal joints.

We will use cells from human tissue which is normally discarded after surgery and an animal model to answer a number of questions. Are stem cells, normally present in the joint synovium (joint lining), responsible for pannus formation in RA? Is the pannus in RA sustained by a diseased stem cell that increases in an uncontrolled manner? When does this start? Our animal model will also allow us to find out if “bad” stem cells are present in the synovium, or if they originate from the bone marrow.

How will the findings benefit patients?

Pharmacological targeting of stem cells in the body could lead to major biomedical breakthroughs in the years to come. This approach is new in rheumatology but is being used successfully in other research areas such as cancer. This study will generate knowledge that will be instrumental for the development of novel drugs to stop these “bad” stem cells and arrest, or even reverse, disease progression and joint damage in RA.