Abstract

EV MEET Cell: An Efficient EV-Target Cell Interaction through Modulation of the Extracellular Environment of Target cell

Sai Kiang Lim, Research Director, A*STAR Institute of Medical Biology

Mesenchymal stromal cells (MSC) have displayed promising therapeutic potential; nonetheless, no FDA-approved MSC product exists due largely to the absence of a reliable potency assay based on the mechanisms of action to ensure consistent efficacy. MSCs are now thought to exert their effects primarily by releasing small extracellular vesicles (sEVs) of 50-200 nm. While non-living MSC-sEV drugs offer distinct advantages over larger, living MSC drugs, elucidating their mechanism of action to develop robust potency assays remains a challenge. A pivotal prelude to elucidating the mechanism of action for MSC-sEV is how extracellular vesicles (EVs) communicate with their primary target cells. Given the inherent inefficiencies of processes like endocytosis, endosomal escape, and EV uncoating during cellular internalization, we propose an alternative EV communication approach, EV-MEET Cell, which stands for EV-Modulation of the Extracellular Environment of Target Cells. This approach involves modifying the external cellular milieu such that signals from a single EV could be transmitted to multiple recipient cells, thereby eliciting a more widespread tissue response.