Positron Emission Tomography- guided treatment of acute myocardial infarctions with extracellular vesicles for optimal reduction of scar formation

Survival after an acute myocardial infarction (AMI) and heart failure has not improved over the last decade because treatment of today does not affect the reperfusion injury, which is induced when an occluded coronary artery is opened by percutaneous coronary intervention (PCI).

The restored blood flow (reperfusion) initiates a vicious cycle of inflammation and activation of heart fibroblasts with subsequent scar formation and loss of functionality, which leads to heart failure.In this project we will restrain the consequences of ischemia-reperfusion injury using administration of extracellular vesicles (EVs), generated from cultured human bone marrow-derived mesenchymal stromal cells, which have proven to be immune modulatory and to preserve the myocardial function in mice after an ischemia-reperfusion injury.

In order to determine the optimal timing and dose of the EVs for maximal therapeutic effect, there is a need to directly follow the activation of fibroblasts in vivo after administration of the EVs.

We will make use of a specially developed Positron Emission Tomography (PET) tracer, that binds to the activated fibroblasts, where the PET signal correlates to both localization and degree of fibroblast activation.

The dosing and timing of EV-delivery will first be developed in an ischemia-reperfusion model in mice (1st and 2nd year) and finally adapt the concept to pigs (3rd year). This project has a clear clinical implication to directly reduce scar formation after AMI.