Developing patient-derived organoids to dissect the cellular & molecular mechanisms underpinning resolving and persistent forms of arthrofibrosis

This award aims to develop patient-derived cell-based organoid models of the knee in healthy and fibrotic conditions, replacing the use of some mice in arthrofibrosis studies.

Arthrofibrosis causes joint stiffening, pain and limited motion and is caused by excessive scar tissue formation, for example after knee replacement surgery. Arthrofibrosis in the shoulder joint uniquely resolves over time whereas fibrosis in the knee and other joints persists. While some therapies delay progression of fibrotic conditions, none reverse fibrosis and fundamental knowledge gaps of which cells and molecules drive fibrosis in different tissues remain. Researchers typically use rodents to study joint disease due to the complexities of modelling in vitro immune system events which drive many joint conditions. Professor Stephanie Dakin aims to develop patient-derived organoids and demonstrate their utility in arthrofibrosis research by determining the underlying mechanisms of disease persistence in knee arthrofibrosis. She will then compare to the pathways in shoulder arthrofibrosis, to identify and test new therapeutic strategies to treat persistent arthrofibrosis.