Extracellular Vesicles in Physiology, Pathology, and Therapy of the Immune and Central Nervous System, with Focus on Extracellular Vesicles Derived from Mesenchymal Stem Cells as Therapeutic Tools

Abstract

Extracellular vesicles (EVs) are membrane-surrounded structures released by most cell types. They are characterized by a specific set of proteins, lipids and nucleic acids. EVs have been recognized as potent vehicles of intercellular communication to transmit biological signals between cells. In addition, pathophysiological roles of EVs in conditions like cancer, infectious diseases and neurodegenerative disorders are well established. In recent years focus has been shifted on therapeutic use of stem cell derived-EVs. Use of stem cell derived-EVs present distinct advantage over the whole stem cells as EVs do not replicate and after intravenous administration, they are less likely to trap inside the lungs. From the therapeutic perspective, the most promising cellular sources of EVs are mesenchymal stem cells (MSCs), which are easy to obtain and maintain. Therapeutic activity of MSCs has been shown in numerous animal models and the beneficial paracrine effect of MSCs may be mediated by EVs. The various components of MSC derived-EVs such as proteins, lipids, and RNA might play a specific therapeutic role. In this review, we characterize the role of EVs in immune and central nervous system (CNS); present evidences for defective signaling of these vesicles in neurodegeneration and therapeutic role of EVs in CNS.

Extracellular Vesicles from Mesenchymal Stem Cells Exert Pleiotropic Effects on Amyloid‐β, Inflammation, and Regeneration: A Spark of Hope for Alzheimer's Disease from Tiny Structures?

“…EVs are in fact endowed with several advantageous properties and possess a higher safety profile with respect to the whole cells; since they do not induce vascular obstruction, they can pass the blood–brain barrier easier than the entire cells, have low immunogenicity, and could be engineered for personalized treatments …”

“…The protective potentials of MSC‐EVs in the brain have been recently demonstrated in both the regulation of the inflammatory response mediated by microglial cells and in the regenerative and maintenance effects of tissue homeostasis . In particular, it has been shown that the administration of MSC‐EVs promotes neurogenesis, angiogenesis, remodeling of nervous processes with the formation of new synapses, and induce axonal plasticity . In addition, MSC‐EVs have been shown to exert immunomodulatory effects (see Box ).…”

Mesenchymal Stem Cell-derived Extracellular Vesicles for Renal Repair

“…MSC-derived EVs express characteristics of their parental MSCs, including the surface markers CD44, CD73, CD90, and CD105, as well as specific EV surface markers, such as CD9, CD63, and CD81 [34-36]. Importantly, MSC-derived EVs contain a vast number of mRNAs, microRNAs and proteins, which mediate the paracrine effects of MSCs by modulating several cellular pathways in recipient cells [30]. …”

“…In addition to the release of cytokines, chemokines, and growth factors, these cells produce and secrete extracellular vesicles (EVs), membrane microparticles that transfer mRNAs, microRNAs, and proteins to recipient cells [29]. Previous studies have shown that MSC-derived EVs transfer enhances proliferation, inhibits apoptosis, decreases inflammation, and promotes angiogenesis by altering the gene expression profile of their target cells [28, 30]. Therefore, delivery of MSC-derived EVs may be an attractive cell-free therapy for renal disease.…”

Strategies to improve the migration of mesenchymal stromal cells in cell therapy

“…Recently, extracellular vesicles (EVs), membrane-surrounded structures released by most cell types, have been recognized as potent vehicles of intercellular communication that transmit biological signals between the cells. Paracrine effects of MSCs may be mediated by EVs [136] . The stromal cell derivedEVs do not replicate like the stromal cells, and they are less likely to become trapped inside the lungs after intravenous administration.…”