Grant: Project Grant

The goal of this project is to understand how tendon cells make tendon, so we can improve how it heals. Tendon injuries are extremely common and affect young and old alike. Tendons can be damaged from intense physical activity or gradually wear out over time. Once tendon is injured, it rarely returns to the preinjury state. Currently in the clinic, we treat the pain and inflammation and hope for scar tissue to restore some of the structural integrity, but tendon is a finely tuned organ with specific biomechanical properties, while a scar is thick disorganized connective tissue which cannot meet the demands put on tendon. This leaves patients in pain and immobilized, which impacts their ability to work and exercise, and deprives them of their independence. A vicious circle ensues, as this state is accompanied by a much higher risk of reinjury. True regeneration means restoring the tissue to the preinjury state and is dependent on stem cells to replace the damaged tissue with new tendon tissue. We have found Mesenchymal Progenitor (MP) cells with the potential to make tendon cells in adult mice, however, there are considerable gaps in our understanding of the molecular processes that drive MPs to become tendon cells. Herein, we address this by using a genetic tool, which allows us to identify, isolate and manipulate MPs in mouse injury models. We will perform a systematic analysis of MPs throughout the healing process to find out what genes they need to activate, and in what order, to generate tendon. Then, with the aim to enhance tendon cell formation and reduce scar tissue deposition, we will strategically perform genetic and pharmacological modifications to affect MP behaviour, and evaluate the consequences on tendon healing outcome parameters. This research will map the path from stem cell to tendon cell and generate leads to uncover targets for therapeutic and tissue engineering strategies that can be used to improve tendon regeneration and mitigate degeneration.