MSC exosome works through a protein-based mechanism of action

Abstract

Mesenchymal stem cell (MSC) exosome specifically defines the 50-200 nm vesicles that are secreted into the extracellular space when multivesicular bodies in the MSC fuse with the plasma membrane. However, the exosome is just one of several 50-200 nm extracellular vesicles (EVs) known to be secreted by cells. Nevertheless, the term 'MSC exosome' is often used to describe populations of 50-200 nm EVs that are prepared from culture medium conditioned by MSCs on the basis that these populations collectively exhibited typical exosome-associated proteins such as endosomal proteins, TSG101 and Alix, and tetraspanin proteins, CD9, CD63 and CD81. They also carry a rich diverse RNA cargo. MSC exosomes are increasingly implicated as the mediator of many of the MSC-associated therapeutic potencies. They elicit therapeutic activity by delivering their cargo of potentially therapeutic proteins and RNAs to the recipient cells. The therapeutic potency of MSC exosomes is usually rationalized on the presence of a biologically relevant protein or RNA in the MSC exosome. In the present paper, we expanded this rationale beyond a physical presence to include biologically relevant concentration, biochemical functionality and the potential to elicit an appropriate timely biochemical response. Based on these, we propose that MSC exosomes most probably work through the protein rather than the RNA.

Keywords: MSC exosome; enzyme; mechanism of action; microRNA; proteome.

Figure 1.. The MOA underpinning the therapeutic efficacy of MSC exosomes could be attributed to their cargo of protein or RNA.

As a first requisite to identifying the candidate molecule, the candidate protein or miRNA that has the potential to elicit the therapeutic response in the target cells must be present in the exosomes. Second, the candidate must be in a biologically functional configuration. In the case of protein enzyme, this property could be directly assessed by enzyme activity. For miRNA to be functional, the exosomal miRNA must either be mature miRNAs in RISCs or pre-miRNAs that could be loaded into RISCs. Third, the candidate protein or miRNA in a therapeutic dose must have sufficient functional activity to elicit the biological response of the target cell.