GMP-compatible extracellular vesicles prevent heart failure after a myocardial infarction through reduction of myofibroblast activation

ABSTRACT: Ischemic heart disease is the leading cause of heart failure and mortality in the Western world. Survival after a ST-Elevation Myocardial Infarction (STEMI) has not improved over the last decade, mostly because revascularization with percutaneous coronary intervention (PCI) may, paradoxically, induce myocardial ischemia-reperfusion (MIR) injury. The injury is orchestrated by macrophages and leads to myofibroblast activation and additional scar formation. Here, we have developed a good manufacturing practice compatible protocol for the generation of an immune modulatory extracellular vesicle (EV)-rich product from bone marrow mesenchymal stromal. In blinded, placebo-controlled MIR models in mice and pigs, the EV product preserved the myocardial function in the mice hearts and was cardioprotective in the pig models of MIR. To facilitate translation to the clinic, we have also developed a positron emission tomography (PET)-based system to longitudinally detect in vivo heart myofibroblast activation and, thereby, the scar formation in mice and humans. The PET system showed that the EV-product significantly reduced myofibroblast activation and the scar size in placebo-controlled MIR-injury models in mice. In conclusion, PET-directed EV-treatment might offer an individualized additive treatment to PCI in order to prevent heart failure after STEMI.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Pierre Sabatier  

LAB HEAD: Jesper Olsen

PROVIDER: PXD064567 | Pride | 2026-06-12

REPOSITORIES: Pride