Vesicle therapy to reduce inflammation after heart surgery

Associate Professor Joy Wolfram, The University of Queensland

Future Leader Fellowship - Level 2

Years funded: 2025 - 2028

Developing effective therapeutics to address cardiac surgery-induced inflammation by leveraging extracellular vesicles

Cardiac surgery in high-risk patients (e.g., elderly, endocarditis, severe heart failure, etc.) leads to inflammatory responses, causing post-operative complications that can progress to multi-system organ failure and death. Inflammatory responses remain clinically unaddressed in such patients, highlighting the need for better approaches for post-operative management to improve quality of life and reduce mortality.

The goal of the project is to develop effective therapeutics to address cardiac surgery-induced inflammation by leveraging extracellular vesicles (EVs). Cells reduce inflammation by releasing EVs that interact with recipient cells to suppress inflammatory pathways. EVs can be isolated and engineered as a new paradigm of anti-inflammatory therapeutics. The versatile bioactive cargo of EVs makes them superior to conventional pharmaceuticals and ideal candidates for treating multifaceted inflammation caused by cardiac surgery.

My vision is to realise the potential of EVs as effective therapeutics for cardiac surgery in high-risk patients who could benefit the most. I will leverage an innovative ex vivo system, large animal model, and EV manufacturing/engineering strategies to generate critical preclinical data for larger scale studies and clinical trials to improve post-operative complications form cardiac surgery in high-risk patients. I collaborate with world-leading cardiothoracic surgeons, making me ideally placed to realise this vision.

I will assess EV therapeutics for cardiac surgery-induced inflammation through the following aims:

1. Evaluate anti-inflammatory effects of EVs in an extracorporeal ex vivo model of blood flow during cardiac surgery.
2. Assess therapeutic effects of EVs in reducing cardiac surgery-induced inflammation in an ovine model.
3. Develop large-scale manufacturing approaches for uniform EV therapeutics.

This project will have impact through advancing knowledge in the EV field and by developing a new paradigm of therapeutics for cardiac surgery complications with the goal of improving post-operative recovery in high-risk patients.