Lead investigator Prof Stephanie Dakin has teamed up with co-investigator Prof Chris Buckley, Prof Andrew Price and surgical colleagues at NDORMS to understand the mechanisms behind fibrosis in the knee with the aim to reduce the number of patients requiring surgery from the condition.
The team are hoping to learn lessons from frozen shoulder, a fibrotic disease affecting the shoulder joint capsule which almost always resolves over time. They plan to model the responses of the cells in the shoulder capsule that bring about a resolution of fibrosis and look for ways to replicate the process in the knee.
Prof Dakin explained: 'By studying frozen shoulder patient tissues, we've been able to identify how the major cell types in the shoulder joint capsule, namely macrophages and fibroblasts, crosstalk to moderate inflammation and resolve fibrosis. We want to use this knowledge to understand the biological cues which we can then apply to the knee joint to help prevent patients developing arthrofibrosis after knee replacement.'
The project, funded by the NC3R's and Rosetrees Trust, will create a cellular atlas of the human knee capsule during three stages: development, health and fibrotic disease. The team will build advanced 3D tissue culture models comprised of patient-derived cells, and compare the cells and molecules directly with those in the shoulder capsule where fibrosis resolves. Not only will the researchers be able to see how the cells behave to resolve fibrosis, they will also be able to test new therapeutics to improve the condition for patients.
As these biological tools are further developed and adopted by scientists studying musculoskeletal disease, this could further support NC3R's aim to reduce, refine and replace the use of animal models to study disease.