Scientists at Brigham and Women’s Hospital have used a new method to acquire cells from tissue samples for use in rheumatoid arthritis research, which could help with the development of new rheumatoid arthritis therapies.
Rheumatoid arthritis affects more than 1.3 million individuals in the United States. The disease affects the joints and causes chronic inflammation and considerable pain and swelling, reducing movement and the function of joints. Inflammation can also occur in other areas of the body.
There are effective rheumatoid arthritis therapies that can ease the symptoms of the disease by targeting pathways and cell types that cause inflammation of the joints. While these rheumatoid arthritis therapies have positive results in some patients, some individuals fail to respond. Further rheumatoid arthritis research is necessary to determine why that is the case.
Researchers are currently looking for biomarkers that could be used to determine whether patients will respond to a particular therapy, and cell samples are required to identify pathways that lead to inflammation to allow them to be targeted.
Due to the complexity of rheumatoid arthritis, identifying new targets and biomarkers is difficult. Before new therapies can be developed, large numbers of cells from a diverse range of patients need to be collected for large-scale rheumatoid arthritis research studies.
The researchers at Brigham and Women’s Hospital wanted to conduct such a large-scale study, but that would require cells to be gathered from multiple locations. This presented a problem. The researchers needed a reproducible method of cell collection and a better process for preserving those cells, since they would need to be sent to a central location where analyses could take place.
The researchers devised a new method of preserving cells to allow large samples to be obtained for the study. The preservation method involved freezing intact synovial tissue samples quickly after acquisition, and transporting them to the testing sites. The researchers then acquired viable cells for the study from those preserved tissues.
Tissues were collected from 10 sites, from 22 biopsies and 36 elective surgical procedures, which yielded 58 synovial tissues for the study. Between 30 and 40 cell types were studied along with thousands of genes, using multiple high-dimensional analyses including single cell RNA sequencing, flow cytometry, and mass cytometry.
Without a large number of cells from a diverse range of patients, it would be difficult to identify inflammation pathways to target. “When applied to large numbers of patients, these analyses have the potential to identify specific inflammatory pathways that define subsets of RA patients, which may eventually help guide treatment decisions,” said Dr, Deepak Rao, lead author of the study.
“We also hope that this approach of cryopreserving viable, intact tissue can be used as a model for centralized analysis of samples from multiple study sites in other rheumatic and inflammatory conditions,” explained Dr. Rao.
The new preservation technique was explained at the annual conference of the American College of Rheumatology and Association of Rheumatology Health Professionals in San Diego.