Exosome Learn

Exosome Learn

Exosomes are emerging as promising nanocarriers for drug delivery and targeted therapies, as alternatives to stem cell therapy.

Exosomes are endosome-derived small membrane vesicles, approximately 30 to 100 nm in diameter. They are released into extracellular fluids by cells in all living systems. Many types of cells generate exosomes which contain proteins and lipids as well as mRNAs and microRNAs (miRNAs).

Exosomes are well suited for small functional molecule delivery and carrying therapeutic cargo. Increasing evidence indicates that they play a pivotal role in cell-to-cell communication.

Additional benefits of MSC-derived exosomes, as compared with transplanted exogenous MSCs, are that the exosomes do not proliferate, are less immunogenic, and are easier to store and deliver than MSCs. These benefits bode well for creation of an off-the-shelf, easy to administer, therapy which could be helpful to a broad base of patients.

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.

Exosomes are more likely 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 are expected to have 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. This is 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:

  1. Determine the mechanisms (central and peripheral effects) of the exosomes underlying improved functional recovery after TBI;
  2. Maximize generation of exosomes by MSCs;
  3. 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;
  4. Refine the isolation procedure for exosomes;
  5. Define the optimal dose and therapeutic time window and potential routes of administration;
  6. Identify the contents of exosomes and modify the content contained in or on exosomes for targeted treatment;
  7. Develop exosomes as a drug delivery system that can cross the blood-brain barrier and facilitate drug penetration into the brain;
  8.  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, while monitoring potential adverse effects; and 
  9.  Advance towards translating these studies into therapies.

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