Journal
NANOSCALE
Volume 12, Issue 38, Pages 19844-19854Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/d0nr04278a
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Funding
- European Union's Horizon 2020 Research and Innovation Programme through the Marie Sklodowska-Curie Individual Fellowship [659175]
- IDT Post Doc Award Program
- Biotechnology and Biological Sciences Research Council Doctoral Training Partnership [BB/N503952/1]
- Imperial College London British Heart Foundation Centre for Research Excellence [RE/13/4/30184]
- British Heart Foundation Studentship grant [FS/16/76/32409]
- Deutsche Forschungsgemeinschaft [KA 4370/1-1]
- Rosetrees Trust
- BHF Centre for Cardiac Regeneration at Imperial College London [RM/17/1/33377]
- GSK through the Imperial College London Engineered Medicines Laboratory Project
- Marie Curie Actions (MSCA) [659175] Funding Source: Marie Curie Actions (MSCA)
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Extracellular vesicles (EVs) represent a promising cell-free alternative for treatment of cardiovascular diseases. Nevertheless, the lack of standardised and reproducible isolation methods capable of recovering pure, intact EVs presents a significant obstacle. Additionally, there is significant interest in investigating the interactions of EVs with different cardiac cell types. Here we established a robust technique for the production and isolation of EVs harvested from an enriched (>97% purity) population of human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs) with size exclusion chromatography. Utilizing an advanced fluorescence labelling strategy, we then investigated the interplay of the CM-EVs with the three major cellular components of the myocardium (fibroblasts, cardiomyocytes and endothelial cells) and identified that cardiac endothelial cells show preferential uptake of these EVs. Overall, our findings provide a great opportunity to overcome the translational hurdles associated with the isolation of intact, non-aggregated human iPSC-CM EVs at high purity. Furthermore, understanding in detail the interaction of the secreted EVs with their surrounding cells in the heart may open promising new avenues in the field of EV engineering for targeted delivery in cardiac regeneration.
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