A novel approach to attain highly purified exosomes for the investigation of cardioprotection (Mr Elias Sulaiman)

Myocardial infarction (MI) is a major cause of death and disability. New strategies to protect the myocardium are required.

Nano-sized extracellular vesicles (sEVs) called exosomes can protect the heart and improve function when administered after MI.

Mesenchymal stromal cells (MSC) are a promising source of sEVs with beneficial properties including the ability to protect against infarction.

However, their mechanism of action remains controversial, and understanding is hindered by the lack of purity or consistency between laboratories in the sEV preparations being used.

We recently established a unique protocol for dual-tagging sEVs with a short, rationally designed epitope tag conjugated to a small, bright Nano-luciferase.

The tagged sEVs can be immunoprecipitated using a specific, medium-affinity recombinant nanobody, and importantly, they can be efficiently eluted from the antibodies and purified for functional studies using gentle conditions. Furthermore, nano-luciferase can be used to trace their cellular uptake and biodistribution.

In this studentship, the student will apply this method to purify sEVs from reversibly immortalised MSC, characterise them to an unprecedented degree, and investigate aspects of their ability to protect the heart.

We anticipate that this approach will allow us to resolve some of the outstanding controversies about sEVs and their mechanism of action.