Cell therapies involving c-kit+ progenitor cells (CPCs) and mesenchymal stem cells (MSCs) have been actively studied for cardiac repair. The benefits of such therapies have more recently been attributed to the release of small extracellular vesicles (sEVs) from the parent cells. These sEVs are 30−180 nm vesicles containing protein/nucleic acid cargo encapsulated within an amphiphilic bilayer membrane. Despite their pro-reparative effects, sEV composition and cargo loading is highly variable, making it challenging to develop robust therapies with sEVs. Synthetic alternatives have been developed to allow cargo modulation, including prior work from the laboratory, to design sEV-like vehicles (ELVs). ELVs are synthesized from the sEV membrane but allow controlled cargo loading. It is previously shown that loading pro-angiogenic miR-126 into CPC-derived ELVs significantly increases endothelial cell angiogenesis compared to CPC-sEVs alone. Here, they expand on this work to design MSC-derived ELVs and study the role of the parent cell type on ELV composition and function. It is found that ELV origin does affect the ELV potency and that ELV membrane composition can affect outcomes. This study showcases the versatility of ELVs to be synthesized from different parent cells and highlights the importance of selecting ELV source cells based on the desired functional outcomes.
This work was supported by grant R01 HL145644 awarded to M.E.D, as well as funding from the Additional Ventures Cures Collaborative. The authors would like to thank the Robert P. Apkarian Integrated Electron Microscopy Core (IEMC), the Emory Flow Cytometry Core (EFCC), and the Emory Integrated Proteomics Core (EIPC), which are subsidized by the Emory University School of Medicine. All three are part of the Emory Integrated Core Facilities. This work was also supported in part by Georgia Institute of Technology's Systems Mass Spectrometry Core Facility.
