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Published on: March 31, 2010
MSC exosome works through a protein-based mechanism of action
Wei Seong Toh1,2, Ruenn Chai Lai3, Bin Zhang3
1Faculty of Dentistry, National University of Singapore, Singapore.
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.
Insights
Mesenchymal stem cell (MSC) exosomes are extracellular vesicles that mediate therapeutic effects. This study proposes that MSC exosome potency primarily relies on protein cargo, not RNA, considering concentration and function.
Area of Science:
- Biomedical Sciences
- Cell Biology
- Regenerative Medicine
Background:
- Mesenchymal stem cells (MSCs) secrete extracellular vesicles (EVs), including exosomes (50-200 nm).
- MSC-derived EVs, often termed 'MSC exosomes', contain proteins like TSG101, Alix, CD9, CD63, CD81, and diverse RNA.
- These vesicles are recognized for mediating MSC-associated therapeutic effects by delivering cargo to recipient cells.
Purpose of the Study:
- To investigate the mechanism underlying the therapeutic potency of MSC exosomes.
- To expand the rationale for MSC exosome therapeutic activity beyond mere presence of cargo.
- To determine whether protein or RNA cargo is the primary driver of MSC exosome therapeutic function.
Main Methods:
- Characterization of MSC-derived EVs, focusing on size (50-200 nm) and associated proteins.
- Analysis of RNA cargo within MSC exosomes.
- Evaluation of protein cargo concentration, biochemical functionality, and response elicitation.
Main Results:
- MSC exosomes possess characteristic exosomal proteins and a diverse RNA cargo.
- Therapeutic potency was assessed based on protein/RNA concentration, functionality, and induced cellular response.
- Evidence suggests that protein cargo plays a more significant role than RNA cargo.
Conclusions:
- MSC exosomes exert therapeutic effects through delivered cargo.
- The functional capacity, concentration, and timely response elicited by protein cargo are key to MSC exosome potency.
- MSC exosome therapeutic mechanisms are likely protein-driven rather than RNA-driven.
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