Exosomes — Extracellular Vesicles: What Are They? Could the “Cargo” Onboard Be Dangerous?

Joseph R. Anticaglia, MD
Medical Advisory Board

Exosomes are microscopic, round, or oval sac-like structures that contain proteins, lipids, RNA, and DNA. They’re produced inside the cell by almost all cell types, and are released into the extracellular space, the space outside the cell. They’re about one 100th the size of a human cell and are also known as Extracellular Vesicles (EVs). A vesicle is a small sac-like structure.

Exosomes are formed when vesicles inside the cell fuse with the plasma membranes, the membrane that surrounds the cell. The combination of vesicles, and plasma membranes brings about the creation of exosomes, and their release into the extracellular space.

Upon entering the extracellular space, exosomes can travel, for instance, by way of the bloodstream to other parts of the body and transfer their “cargo” (protein, lipids, DNA, RNA) into other cells. Exosomes carry out the transfer of the content of their cargo to recipient cells by fusing with the recipient’s cell membrane, or with the recipient’s proteins located on the outside of their cell membrane.

Why the Intense Interest in Extracellular Vesicles?

EVs are of great interest to the scientific community since they are thought to provide cell-to- cell communication important for the body to function properly, and their potential role as biomarkers of disease, Scientists are also excited about their diagnostic, monitoring, and therapeutic possibilities. Of concern, however, is that they also transfer harmful proteins and genetic material between cells.

Potential Benefits of Extracellular Vesicles

• Cell Communication; One way to think of exosomes is to picture it as a UPS network delivering information, messages, and “cargo” to different regions of the body.
• Regenerative Potential is the ability to repair tissues through repopulation, and differentiation. Studies suggest EVs are useful in regenerating damaged tissues like skin, bone and cartilage by promoting cell proliferation, and migration to the damaged tissue.
• Blood Brain Barrier: EVs can cross the blood brain barrier increasing their potential use for neurologic diseases.
• Immune Response: Extracellular vesicles are thought to help immune response by activating antibodies, inflammatory factors, or killer T cells. Paradoxically, they’re thought to have the opposite effect.
• Drug Delivery: Drug information conceivably, is packaged into EVs, and the drug “cargo” is delivered to the indicated recipient cells.
• Diagnostic Potential: EVs have the diagnostic potential as a non-invasive biomarker to detect, and monitor the status of different conditions.
• Cardiovascular Disease: Extracellular vesicles is thought to have great potential in treating CV disease
• Waste Management: EVs serve to remove unwanted, or degraded proteins.

Potential Harmful Effects of Extracellular Vesicles

• Cancer: EVs might tell us about the location, spread, and growth of cancer; but a worrisome downside of these vesicles is the potential for the cancer to communicate, and spread to other regions of the body. It’s thought that EVs-exosomes, laden with a “cargo” of cancer cells plays a role in the spread of cancer to other cells.
• Extravesicular vesicles can contribute to tumor growth, drug resistance, and promote the growth of new blood vessels (angiogenesis) which contributes to the spread of cancer.
• Diseases: Sometimes EVs can cause certain diseases to spread to different parts of the body. They may cause T cell death preventing immune cells from killing cancer. Paradoxically, they may have the opposite effect on the immune system.

The increased interest in exosomes — extracellular vesicles has grown exponentially over the past twenty years fueled by their potential diagnostic and therapeutic applications. Exosomes can be found in almost every bodily fluid. They can be isolated using various techniques, and visualized under a microscope.

They were originally thought to function as a means to eliminate unwanted, unnecessary material from cells. Research has highlighted their critical role in cell-to-cell communication, and their potential benefits. Other studies have demonstrated the dark side of exosome.

Many challenges face the scientific community doing EVs research, particularly since extracellular vesicles have the potential of being both disease curing, and disease promoting. Researchers are laboring to overcome the safety concerns posed by the dangerous “cargo” in extracellular vesicles that can be delivered to different parts of the body.

Glossary

Vesicles — are small, membrane bound sacs within the cell that can fuse with the plasma membrane to release their contents outside the cell. The process is a form of active transport, and is called exocytosis.

Angiogenesis is the development, and formation of blood vessels.

Endosome — a sac found within a cell.

FDA: As of January 2024, the FDA has not approved any exosome products.

References

1. Clayton Bolt, Raghu Kalluri, Cancer exosomes: Mini cells packed with potential for treatment and diagnostics; MD Anderson Center; June 16, 2021
2. Yvonne Couch, et al; A brief history of nearly EV‐erything — The rise and rise of extracellular vesicles; J Extracell Vesicles, Dec 17, 2021
3. Eileen Tzng et al; Current challenges surrounding exosome treatments; Extracellular Vesicle, Volume 2, December 2023, 100023
4. Girijesh K. Patel, Ajay P. Singh, Exosomes, in Diagnostic and Therapeutic Applications of Exosomes in Cancer; Science Direct. 2018
5. Atilla Engin; Dark-Side of Exosomes; Adv Exp Med Biol, 2021
6. Chris Centeno, MD; Exosome Products Remain Unapproved Drugs: Kimera Labs; Jan 18, 2024
7. Julien M. Essola et al; Exosome regulation of immune response mechanism: Pros and cons in immunotherapy; Bioact Mater, Feb 2024
8. Hui Jing et al; Exosomes and regenerative medicine state-of-the-art and perspectives; Translational Research, 1018
9. FDA; Consumer alert on regenerative medicine products including stem cells and exosome; July 22, 2020,
10. ASRA; Exosomes: The Good, The Bad, and The Ugly; May 12, 2002

This article is intended solely as a learning experience. Please consult your physician for diagnostic and treatment options.