Extracellular vesicles – exosome tech
Extracellular vesicles (EVs) have emerged as promising nanocarriers for drug delivery and targeted therapy, as alternatives to stem cell therapy. EVs are endosome-derived small membrane vesicles, approximately 30 to 150 nm in diameter, and are released into extracellular fluids by cells in all living systems. They are generated by many cell types and contain not only proteins and lipids but also mRNAs and microRNAs (miRNAs).
EVs are well suited for small functional molecule delivery, and increasing evidence indicates that they have a pivotal role in cell-to-cell communication.
In contrast to transplanted exogenous MSCs, the MSC-derived EVs do not proliferate, are less immunogenic, and are easier to store and deliver than MSCs
Extracellular vesicles derived from MSC
EVs as therapeutic agents
MSC-derived EVs have been examined to support regeneration in the context of numerous diseases such as autism, stroke, traumatic brain injury, Parkinson’s disease and Alzheimer’s disease.
As was shown By Prof. Offen team, when intranasally administered, EVs can pass the Blood Brain Barrier (BBB) and are better retained in injury sites in the brain/CNS than when delivered intravenously. Moreover, EVs may be loadable with an array of therapeutic cargos for specific diseases.
EVs “Homing” To Damaged Areas At Mice Brain Models
Intranasal MSC-Exosome home specifically to spinal cord lesion
EVs are promising therapeutic agents because their complex cargo of proteins and genetic materials has diverse biochemical potential to participate in multiple biochemical and cellular processes, an important attribute in the treatment of complex diseases with multiple secondary injury mechanisms involved, such as TBI.
EVs are more amenable to development as an “off-the-shelf” therapeutic agent that can be delivered to patients in a timely manner. They also reduce the safety risks inherent in administering viable cells such as the risk of occlusion in microvasculature or unregulated growth of transplanted cells.
As natural delivery vehicles, EVs advance the development of RNAi-based therapeutics in central nervous system (CNS) diseases, as RNAi delivery is hampered by the BBB, susceptibility to nuclease degradation, and lack of cell-specific targeting. As such, intranasal exosome administration has broad potentials and offers an alternative to cell transplantation in treating Spinal Cord Injuries.
Further investigation is warranted to take full advantage of regenerative potential of cell free MSC-derived EVs, including the choice of MSC sources and their culture conditions, the optimized isolation procedure and the optimal dose and therapeutic time window, as these have been shown to impact the functional properties of the EVs.