Periodic Reporting for period 2 - EVICARE (Extracellular Vesicle-Inspired CArdiac Repair)
Reporting period: 2019-03-01 to 2020-08-31
More than 3.5 million new people are diagnosed with heart failure every year in Europe, with a long-term prognosis of 50% mortality within four years. There is urgent need for more innovative, regenerative therapies with the potential to change the course of the condition. Prof Dr Joost Sluijter at University Medical Center Utrecht is developing a promising therapy: stimulating cardiac repair with extracellular vesicles that are derived from progenitor cells. Membrane-encapsulated packages, containing a cocktail of stimulating factors, secreted by these early descendants of stem cells, could have a potent healing capacity. With the ERC grant, Prof Dr Sluijter aims 1) to improve delivery of these extracellular vesicles, 2) better understand their mechanism of action, and 3) design ways to stimulate their production and release by progenitor cells.
2) To explore and determine functional targets of our EVs, we started several projects on a cell- and organ level. For down-stream functional testing, we have established now multiple endothelial cell assays to study their behaviour, observed that isolated EVs have effects on different immune cells, and observed that fibrosis can be modulated upon EV exposure, however, high dosing is essential to achieve this.
3) To determine if EV release by progenitor cells can be stimulated, we explored the maximum effect that can be expected by interfering with endolysosomal trafficking. Although this was successful, we also realized that EV release can only be stimulated in a limited way and therefore focussed on other aspects to improve their production. We achieved higher functionality of extracellular vesicles by implementing different isolation techniques, including size-exclusion chromatography, by using different columns for their isolation, and introduced an alternative method for the biofabrication of cell-derived nanovesicles, moreover we implemented bioreactors for cell culture.