Therapeutic potential of mesenchymal stem cell-derived extracellular vesicles as novel cell-free therapy for treatment of autoimmune disorders

Over the past decades, new light has been shed on the efficiency of Mesenchymal Stem Cells (MSCs) in the treatment of autoimmune diseases. The therapeutic functions of MSCs partly stem from their well-recognized ability to efficiently modulate immune responses and it is well substantiated that MSC secretory components, in particular extracellular vesicles (EVs), play a critical role in this immunomodulation. In fact, almost any cell type can generate and release EVs under both pathological and physiological conditions and these nano-sized particles are believed to greatly contribute to homeostasis and cell-cell communication through transportation of a wide variety of biomolecules including nucleic acid, signaling lipids, regulatory proteins, transcription factors, cytokines, and growth factors. Lamentably, despite exhibiting promising results in both animal experiments and clinical trials, MSC therapy is still largely restricted to the experimental stage due to its critical pitfalls and drawbacks such as safety issues, poor cell survival, immune rejection and high cost. On the other hand, MSC-derived EVs, which ideally reflect the exact biophysical features of MSCs, are considered to be much safer and more effective than MSCs themselves. Therefore, introducing alternative approaches based on MSC-derived EVs can offer appreciable promise in overcoming the limitations and practical challenges observed in cell-based therapy and thus the extracellular vesicles of MSCs may also provide a far more potent therapeutic strategy for immune-related disorders. In this review, we first focus on the properties of MSC-derived EVs and then we shall provide valuable insight regarding their beneficial therapeutic opportunities to further compare this alternative approach with conventional MSC therapy. Finally, we will attempt to summarize the current findings on the influences of MSC-derived EVs on autoimmune disorders, offering a potential alternative avenue towards treatment of autoimmune diseases.