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 100 nm in diameter, and are released into extracellular fluids by cells in all living systems. Exosomes are small-membrane vesicles of
endosomal origin with a size of 30–120 nm in diameter. 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 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.
MSC-derived exosomes have shown promise in the field of regenerative medicine including treatment of TBI, and 3D MSC culture further enhances generation of exosomes and therapeutic effects.
Exosomes 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.
Unlike transplantation of exogenous neural stem/progenitor cells, MSC-derived exosomes that stimulate endogenous neural stem/progenitor cells to repair injured brain may have several main advantages including:
a) no ethical issue of embryonic and fetal cells
b) less invasiveness.
c) low or no immunogenicity
d) 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.
The ongoing and next steps for exosome research in the translational regenerative medicine would be:
- Determine the mechanisms (central and peripheral effects) of the exosomes underlying improved functional recovery after TBI,
- Maximize generation of exosomes by the MSCs,
- Identify the optimal sources of cells used for generating exosomes and determine potential effects of age and sex of donor cells on exosome generation and contents
- Refine the isolation procedure for exosomes
- Define the optimal dose and therapeutic time window and potential routes of administration
- Identify the contents of exosomes and modify the content contained in or on exosomes for targeted treatment
- Develop exosomes as a drug delivery system that can cross the blood-brain barrier and facilitate drug penetration into the brain
- Scale up cell manufacturing and exosome preparation by developing and refining 3D culture methods such as scaffolds, or tissue-engineered models, cell spheroids, and micro-carrier cultures, monitor potential adverse effects
- Move towards translating these studies into therapies.