Exosomes have emerged as promising nanocarriers for drug delivery and targeted therapy, as alternatives to stem cell therapy.
Exosomes 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).
Exosomes 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 exosomes do not proliferate, are less immunogenic, and are easier to store and deliver than MSCs
Exosomes derived from MSC
Exosomes derived from MSCs (MSC-Exo) have been extensively characterized regarding their proteins, lipids, and RNA profiles. MSC-derived exosomes 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, exosomes can pass the BBB and are better retained in injury sites in the brain/CNS than when delivered intravenously. Moreover, exosomes may be loadable with an array of therapeutic cargos for specific diseases.
Exosomes “homing” to damaged areas at mice brain models
Intranasal MSC-Exosome home specifically to spinal cord lesion
As natural delivery vehicles, exosomes 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 SCI.
MSC-derived exosomes that stimulate endogenous neural stem/progenitor cells to repair injured brain may have several main advantages including:
- No ethical issue of embryonic and fetal cells
- Less invasiveness
- Low or no immunogenicity
- Low or no tumorigenicity
Exosomes 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.
Further investigation is warranted to take full advantage of regenerative potential of cell free MSC-derived exosomes, including the choice of MSC sources and their culture conditions, as these have been shown to impact the functional properties of the exosomes.