Researchers in New York have investigated the mechanism of action of extracellular vesicles, also called exosomes, secreted by mesenchymal stem cells (MSC). Their research highlights that MSC-derived exosomes involved in cardiac regeneration act by an increase in angiogenesis, an anti-apoptotic effect on cardiomyocytes, cell proliferation, and a decrease of collagen production by cardiac fibroblasts.
Exosomes derived from MSCs have attracted great interest due to their reported regeneration properties. It is well accepted that MSCs' role in regeneration is due to the exosomes that they secrete. Indeed, extracellular vesicles have shown healing behaviour in multiple conditions: inflammatory diseases, cardiac issues, neurological disorders and liver fibrosis. Because the exosome field is novel, however, the mechanisms by which they trigger those healing processes are not clearly identified yet.
Juliane Nguyen and her team at the University at Buffalo investigated the content of exosomes produced by MSCs to explain their therapeutic benefits. They modified the exosomes to highly express some miRNA and thus increase the target range of the exosomes.
They found 23 miRNA that were expressed at a significant level. Those 23 miRNA are postulated to affect 5481 genes, which are involved mainly in cardiovascular development, pathways related to cell death and growth, angiogenesis and fibrosis.
This research helps investigators understand how MSC exosomes function so they can more easily predict the outcomes of further studies. This work also shows that modification of exosome by incorporation of miRNA into the producing cell is feasible and allows the design of exosomes tailored to particular requirements.