The Power of Exosomes

The term “exosomes” has frequently been in the news in recent years. They have been known to biologists since their discovery in the 1980s, but they remain something unknown to most other people. As their relevance in the pharmaceutical and medical field increases, we want to explain in simple ways what exosomes are, and why they are disrupting science.

A lot of people assume that exosomes are stem cells - but they are not. Exosomes are defined as very small extracellular vesicles which are produced and released from most mammalian cells. Vesicles are delimited particles which have a lipid bilayer around them to protect the cargo it is carrying. A simple way to imagine them is by thinking of little lipid bubbles that contain small molecules.

The purpose of exosomes is to transport molecules between the cell and its surrounding. In other words, the cell releases exosomes to communicate with other cells and tissues. Through exosomes, cells can manage physiological processes like coagulation, inter-cellular signalling and waste management.

Exosomes are present in biological fluids like blood and urine, and can also be found in tissues.

Exosomes were first discovered in 1983 in immature red blood cells by Stahl and his team¹ as well as Johnstone et al. in the same year². The term “exosome” was coined by Johnstone a few years later³.

These studies showed that intra-luminal vesicles (ILVs) generated in multi-vesicular bodies can be released to the space outside the cell through fusion with the plasma membrane.

These insights, though impressive, did not spark much interest in exosomes within the scientific world for a few decades. It was not until the early 2000s when the potential of exosomes was recognized, which is evident when looking at the significant increase in publications (115 publications in 2006, 1010 publications in 2015)⁴.

Exosome content can be proteins, lipids and nucleic acids. The content of exosomes is not only cell-type specific, but also influenced by the condition of the cell. This means that dependent on the health and current status of the cell, it will release different types of cargo into extracellular space.

One outstanding property of exosomes is that they can mediate regenerative outcomes after injuries or during acute phases of a disease, if they are released from stem cells. Exosomes from mesenchymal stem cells, for instance, were found to activate several signalling pathways which are important in bone fracture repair and wound healing. These exosomes also participate in the regulation of immune-mediated responses and inflammatory diseases.

Exosomes have also been known to contain numerous disease-associated cargos, because they can be released from sources such as cancer cells, or carry neurodegenerative associated peptides. However, the mechanisms by which disease-associated factors spread between cells still remains poorly understood.

Are exosomes extracellular vesicles? Or are they two different things?

Exosomes are in fact a sub-type of extracellular vesicles (EVs). EVs are generally defined as membrane-bound particles which are released from almost all known cells. They contain cargo and cannot replicate. EV sizes range from 20nm to 10µm; however, the majority of EVs is smaller than 200nm.

The release of exosomes from the cell is via so-called multivesicular bodies, which fuse with the cell surface, the outer cell membrane, and set the vesicles free. The size of exosomes is limited by that of the parent multivesicular body. Because of this, exosomes are generally smaller than most other EVs, with a typical diameter range from 30 to 150nm.

EVs have a variety of biological functions, such as elimination of unwanted materials, transfer of functional proteins and RNA, molecular recycling, communication with other cells and others.

Besides exosomes, there are other types of EVs, such as apoptotic bodies and ectosomes. They are derived from cells undergoing apoptosis and plasma membrane shedding, and thus have different functions.

Exosomes can be a very versatile tool in pharmaceutical engineering, with the potential to change medicine in many different ways. Here are some areas where exosomes can help:

• Regenerative Medicine: Exosomes from stem cells are known to play a substantial role in wound repair, tissue regeneration and immune response. Applying these regenerative substances in a condensed and targeted way can accelerate natural regenerative processes in the body.
• Diagnostics: EVs are proposed to play a role in spreading of disease. Specific exosome levels can be elevated in the serum of cancer patients or patients with neurodegenerative diseases compared to controls. Thus, exosomes can be potential biomarkers to help detect specific pathologies in patients.
• Therapeutics: Many studies have shown that the content of exosomes can lead to tumor invasion and metastasis, as well as neural cell death in neurodegenerative diseases. If the cargo is manipulated, exosomes can be excellent carriers of therapeutics and drugs, altering and maybe even reversing these disease-driven effects in patients. Another example are patient-derived exosomes, which are being investigated as a new cancer immunotherapy in several clinical trials.
• Vaccines: The possibility of engineered exosomes as vaccines for different diseases, such as COVID-19, is currently being investigated.

What is the super power of exosomes? What are the advantages of exosomes?

Exosomes are the delivery men of the cell, with the potential to be excellent drug carriers. With their ability to transport many different types of molecules, they can serve as a versatile engineering platform for various purposes, such as in regenerative medicine, cancer therapies, diagnostics and as vaccines.

As a component that is naturally released from the cell, their structure is simple, yet it allows them to enter all areas of the body. When combined with specific cargo such as drugs or RNA, they have the potential to reach places that are otherwise difficult to reach for the drug by itself. Additionally, the uptake of drugs when packed in exosomes was shown to be significantly increased.

Another advantage of exosomes is that they can be manipulated in vitro, which means that they can be engineered under controlled conditions in the lab.

All of these reasons combined make exosomes the incredible biological tool it is.

We previously wrote an in-depth article on stem cell therapy costs, amongst them infusion therapy with exosomes. Click here to read the article on exosome therapy costs.

As previously explained, there are many different treatment possibilities that are currently being researched. The majority of these treatment options are still under development and for the most part not available to patients yet.

However, exosomes are already offered as a therapeutic measure in regenerative medicine. Exosomes from patient-derived stem cells, for instance, are offered at ANOVA. Known as the Stem Cell Secretome, this therapy employs the sum of all naturally released bioactive compounds from the stem cell, such as exosomes, growth hormones, cytokines and RNAs, to enhance the body’s own regenerative processes. These can be applied for a variety of diseases, such as

• Orthopaedic issues (i.e. knee injury, degenerative disc disease, osteoarthritis)
• Neurodegenerative diseases (i.e. multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer’s disease, Parkinson’s disease)
• Spinal Cord Injury
• Lyme Disease
• Erectile Dysfunction

and others.

If you would like to receive more information on currently available treatment options containing exosomes, contact us to request a consultation with our medical professionals.