Extracellular Vesicles of Mesenchymal Stem Cells: Therapeutic Properties Discovered with Extraordinary Success

Abstract

Mesenchymal stem cells (MSCs), the cells distributed in the stromas of the body, are known for various properties including replication, the potential of various differentiations, the immune-related processes including inflammation. About two decades ago, these cells were shown to play relevant roles in the therapy of numerous diseases, dependent on their immune regulation and their release of cytokines and growth factors, with ensuing activation of favorable enzymes and processes. Such discovery induced great increase of their investigation. Soon thereafter, however, it became clear that therapeutic actions of MSCs are risky, accompanied by serious drawbacks and defects. MSC therapy has been therefore reduced to a few diseases, replaced for the others by their extracellular vesicles, the MSC-EVs. The latter vesicles recapitulate most therapeutic actions of MSCs, with equal or even better efficacies and without the serious drawbacks of the parent cells. In addition, MSC-EVs are characterized by many advantages, among which are their heterogeneities dependent on the stromas of origin, the alleviation of cell aging, the regulation of immune responses and inflammation. Here we illustrate the MSC-EV therapeutic effects, largely mediated by specific miRNAs, covering various diseases and pathological processes occurring in the bones, heart and vessels, kidney, and brain. MSC-EVs operate also on the development of cancers and on COVID-19, where they alleviate the organ lesions induced by the virus. Therapy by MSC-EVs can be improved by combination of their innate potential to engineering processes inducing precise targeting and transfer of drugs. The unique properties of MSC-EVs explain their intense studies, carried out with extraordinary success. Although not yet developed to clinical practice, the perspectives for proximal future are encouraging.

Dental Pulp Stem Cell-Derived Secretome and Its Regenerative Potential

“…Modulation of adipose-derived MSCs with lipopolysaccharide increased the levels of the tumor necrosis factor alpha (TNF-α) and IL-6 and increased the regenerative profile of the secretome [ 83 ]. Releases by MSCs vesicles are easy to collect, and their therapeutic possibilities have also been analyzed [ 11 , 17 , 84 , 85 ]. A vesicle including EXs is usually isolated from stem cells according to the standard protocol.…”

Thinking Quantitatively of RNA-Based Information Transfer via Extracellular Vesicles: Lessons to Learn for the Design of RNA-Loaded EVs

“…As an example, mesenchymal stem cell (MSC) based cell therapies (from whom a large fraction of EVs potential drug products are derived) can hardly be explained by one specific pathway, and is now considered to be the result of a multifactorial effect involving both IDO-1 [115], PGE2, Nitric oxide [116], TGF-β1, IL-10, VEGF, HGF, mitochondrial transfer [117], etc. It is therefore very likely that MSC-EVs would also benefit from this pleiotropic effect as MSC-EVs are now reported to be the mediator of MSC therapeutic effect [118]. Some teams either tried to inhibit [3,6,7,[119][120][121][122] or activate particular pathways [4] that were expected to be involved in the MSC-EV mechanism of action and have shown that in both cases the results were not unequivocal, each pathway having been only responsible for a fraction of the effect.…”

The immunology and immunotherapy for COVID-19

“…Furthermore, the potential of COVID-19 treatment can be improved by modifying the extracellular vesicles of MSCs (Ref. 109).…”