EVolution sFoF
Lead Research Organisation:
Aston University
Department Name: College of Health and Life Sciences
Abstract
Inflammation, the most important response of our 'Innate Immune System', is a normal defence mechanism that protects from infection and repairs damage caused by trauma (e.g. wounds). However, the full benefits of inflammation are only realised when the response is turned off and the infected or traumatised tissue is returned to normal. This process is known as 'resolution' and is essential to successful wound healing facilitated by immune cells. When this process is defective it can 'stall' leading to damaging chronic inflammation and non-healing wounds.
By studying the resolution of inflammation and understanding the mechanisms by which immune cells communicate with each other, we have identified crucial factors that drive resolution and thus support wound healing. These factors are small membrane bags (called extracellular vesicles: EV) which carry important cargo - active signals that flick the switch in inflammation from defence to repair. This switch is present in important immune cells - macrophages - and switches the cell from an M1 (defence) phenotype to an M2 (repair) phenotype to resolve inflammation. EV are therefore crucial in resolving inflammation.
Why is this important? Poor wound healing is a major challenge especially with the advancing age of our population and incidence of important co-morbidities such as diabetes. Estimates suggest that each year 3.8 million patients are managed by the NHS for wounds, with over 130 million patient visits from healthcare staff, at an annual NHS cost of £8.3 billion, of which £5.6 billion is associated with managing non-healing (chronic) wounds. Consequently, there is an urgent and unmet need to understand and exploit the immune control that is impaired with ageing and to develop novel approaches to promote wound healing. In chronic (non-healing wounds) the resolution is 'stalled' in the inflammatory phase i.e. the switch is inactive in chronic wounds and our work has identified a route to reactivation of this switch. This proposed programme will exploit this to achieve impact in wound healing therapies by producing EV loaded with the appropriate 'switch' cargo.
Our proposal brings together a strong multi-disciplinary team and cutting-edge technology to undertake key technical developments to move our research to the next stage of exploitation as a product to benefit wound healing. To do this we will take industry standard cell lines used for production of therapeutic agents and engineer them to carry the active cargo needed for switching to repair. We will then prove the ability of these engineered EV to 'flick the switch' in inflammation to repair in a manner that supports effective wound healing.
This programme of work will deliver for the first time EV engineered to carry inflammation controlling cargo with a proven benefit in wound healing. This novel and fundamental development will have a significant impact in the field of wound healing and regenerative medicine. Our use of industry relevant cell and culture systems de-risks the programme for further development at the end of this project, ensuring the outcomes of our programme can be progressed rapidly to clinical trials.
By studying the resolution of inflammation and understanding the mechanisms by which immune cells communicate with each other, we have identified crucial factors that drive resolution and thus support wound healing. These factors are small membrane bags (called extracellular vesicles: EV) which carry important cargo - active signals that flick the switch in inflammation from defence to repair. This switch is present in important immune cells - macrophages - and switches the cell from an M1 (defence) phenotype to an M2 (repair) phenotype to resolve inflammation. EV are therefore crucial in resolving inflammation.
Why is this important? Poor wound healing is a major challenge especially with the advancing age of our population and incidence of important co-morbidities such as diabetes. Estimates suggest that each year 3.8 million patients are managed by the NHS for wounds, with over 130 million patient visits from healthcare staff, at an annual NHS cost of £8.3 billion, of which £5.6 billion is associated with managing non-healing (chronic) wounds. Consequently, there is an urgent and unmet need to understand and exploit the immune control that is impaired with ageing and to develop novel approaches to promote wound healing. In chronic (non-healing wounds) the resolution is 'stalled' in the inflammatory phase i.e. the switch is inactive in chronic wounds and our work has identified a route to reactivation of this switch. This proposed programme will exploit this to achieve impact in wound healing therapies by producing EV loaded with the appropriate 'switch' cargo.
Our proposal brings together a strong multi-disciplinary team and cutting-edge technology to undertake key technical developments to move our research to the next stage of exploitation as a product to benefit wound healing. To do this we will take industry standard cell lines used for production of therapeutic agents and engineer them to carry the active cargo needed for switching to repair. We will then prove the ability of these engineered EV to 'flick the switch' in inflammation to repair in a manner that supports effective wound healing.
This programme of work will deliver for the first time EV engineered to carry inflammation controlling cargo with a proven benefit in wound healing. This novel and fundamental development will have a significant impact in the field of wound healing and regenerative medicine. Our use of industry relevant cell and culture systems de-risks the programme for further development at the end of this project, ensuring the outcomes of our programme can be progressed rapidly to clinical trials.
