Exosome Therapy Reduces Scarring and Heart Failure Following a Heart Attack
The heart regenerates poorly in comparison to other tissues, and the maladaptive inflammation that occurs following a heart attack does not help the situation. Fibrosis and scarring occurs in inflamed heart tissue, causing loss of function and heart failure. Stem cell therapies and the use of exosomes derived from stem cells are well demonstrated to reduce unwanted inflammation in animal studies, and are fairly widely used in the medical tourism industry. Here researchers report on the assessment of the ability of an exosome therapy to reduce heart failure following an induced heart attack in pigs, showing that it reduces the formation of scar tissue and helps to maintain heart function.
Myocardial ischemia-reperfusion (MIR) injury drives adverse remodeling and heart failure after ST-elevation myocardial infarction (STEMI), yet no therapy directly targets the fibrotic response. Here, we developed a good manufacturing practice-compatible extracellular vesicle (EV)-enriched secretome from bone marrow mesenchymal stromal cells and identified a laminin-521-based production strategy suitable for clinical translation.
The EV-enriched secretome exhibited in vitro immunomodulatory activity, and in murine MIR-injury models, treatment preserved left ventricular ejection fraction, reduced platelet-derived growth factor receptor beta (PDGFRβ)-associated myofibroblast activation quantified by positron emission tomography (PET) imaging, attenuated fibrosis, and promoted reparative macrophage polarization.
In a clinically relevant porcine ischemia-reperfusion model, intracoronary administration was cardioprotective. We further developed a clinically approved PDGFRβ-targeted PET-imaging platform for longitudinal assessment of fibrotic activity in STEMI patients, where preliminary observations suggest that myofibroblast activation persists for up to 2 months after STEMI in selected patients. Together, these findings establish a translational therapeutic-diagnostic framework for individualized management of MIR injury.