Healthcare News

Exosomes: A brief introduction into the tiny messengers shaping human health

If the debate surrounding germ theory and terrain theory challenges the veracity of viruses, then in a similar way, exosomes challenge the very foundation of person-to-person viral transmission. Our understanding of the complexities of exosomes is still in its infancy but let us take a closer look into what we know so far.

What are exosomes?

Exosomes are small extracellular vesicles (EVs) that typically range in diameter from 30 to 150 nanometers and are encased in a lipid membrane. These vesicles are secreted by nearly all types of cells within the body and play a critical role in facilitating communication between different cell types. Initially, exosomes were thought to merely serve as a means for cells to dispose of waste products or unwanted materials, but current research reveals that their functions are far more complex and multifaceted. They are now recognized as key players in the transfer of various biomolecules, including proteins, lipids, and RNA molecules, from one cell to another, thereby influencing and regulating numerous cellular processes, which has significant implications for understanding intercellular communication and potential therapeutic applications (Raposo & Stoorvogel, 2013).¹

The role of exosomes in human health

Exosomes contribute significantly to a multitude of physiological processes within the human body, including the regulation of immune responses, tissue repair, and the maintenance of cellular homeostasis. These small extracellular vesicles play a crucial role in intercellular communication, facilitating the transfer of proteins, lipids, and genetic material between cells. Their diverse functions highlight their importance in both health and disease, as they are involved in various biological activities and signaling pathways. Here are some key roles that exosomes play in enhancing our understanding of cellular dynamics and their implications for therapeutic applications:

Cell-to-cell communication:

Exosomes function as essential vehicles for transporting bioactive molecules, including microRNAs (miRNAs), messenger RNAs (mRNAs), and proteins, to recipient cells. This intricate transfer of molecular information plays a significant role in influencing gene expression and can lead to alterations in cellular behavior. Such changes are crucial for maintaining the proper functions of healthy tissues and ensuring overall cellular communication and interaction within the body (Tkach & Thery, 2016).²

Immune system modulation:

Exosomes play a crucial and pivotal role in modulating and influencing immune responses. Depending on the specific context and circumstances, they can either activate or suppress a variety of different immune functions, thereby contributing significantly to the overall balance and homeostasis of the immune system (Robbins & Morelli, 2014).³

Tissue regeneration and repair:

Exosomes that are derived from stem cells have demonstrated significant potential in enhancing the processes of tissue repair and regeneration. This remarkable ability to facilitate recovery positions these exosomes as potentially invaluable resources in the ever-evolving field of regenerative medicine, thereby opening up new and innovative avenues for therapeutic strategies and interventions (Lai et al., 2013).⁴

Neuroprotection:

Exosomes play a critical role in supporting the survival and proper functioning of neurons, which has significant implications for various neurodegenerative diseases, including Alzheimer’s and Parkinson’s. Their unique ability to transport protective factors can help mitigate neuronal damage and promote overall brain health and resilience, potentially offering new avenues for therapeutic interventions (Saeedi et al., 2019).⁵

Certain exosomes possess the ability to transport oncogenic molecules that significantly enhance tumor growth, promote metastasis, and contribute to drug resistance, thereby positioning these exosomes as promising potential targets for innovative cancer treatment strategies (Kalluri & LeBleu, 2020).⁶

Exosomes as vehicles for viral spread

While exosomes provide numerous advantages in facilitating cellular communication and interaction, they simultaneously play a more insidious role in the biological landscape: aiding in the spread of viruses. Certain viruses cleverly exploit the exosomal pathways to evade detection and attack by the immune system, thereby enhancing their infectivity and enabling the dissemination of infection to distant cells throughout the body. Here is a closer look at how various viruses manipulate and exploit exosomes to their advantage:

Mimicking exosomes:

Numerous viruses, such as the human immunodeficiency virus (HIV) and the hepatitis C virus, cleverly hijack the cellular machinery that is responsible for the production and secretion of exosomes. By engaging in this cunning strategy, these viruses are able to package and disseminate essential viral components within exosomal vesicles, thereby enhancing their ability to infect and spread (Meckes & Raab-Traub, 2011).⁷

Facilitating immune evasion:

Viral particles that are encapsulated within exosomes have the ability to successfully evade immune surveillance mechanisms. This evasion can ultimately result in persistent infections that are notably challenging to eliminate, making treatment difficult and complicating the overall management of the infection (Nolte-‘t Hoen et al., 2016).⁸

Enhancing infectivity:

The exosome-mediated delivery of viral RNA and proteins to uninfected cells has the potential to significantly boost viral replication rates, thereby accelerating the overall progression of the disease. This phenomenon highlights the critical role that exosomes play in viral pathogenesis, as demonstrated by the research conducted by Schorey et al. in 2015.⁹

Viruses have the capability to utilize exosomes as a means to transmit resistance factors to nearby cells, consequently diminishing their susceptibility to various antiviral medications, as noted by Mack et al. in the year 2000.¹⁰

Why one Person’s exosomes cannot function in another Person

Despite their versatile and beneficial roles in various biological processes, exosomes are highly specific to the individual from whom they originate. This intriguing specificity raises a critical and thought-provoking question: why can exosomes derived from one person not function optimally in the body of another individual? Here are several compelling reasons for this fascinating phenomenon:

Personalized molecular cargo:

Exosomes are known to transport molecular signatures that are distinctly aligned with the host's unique genetic composition, immune status, and specific cellular environment. Consequently, exosomes derived from one individual may exhibit incompatibility when interacting with another person's biological system, leading to potential challenges in therapeutic applications and biological interactions (Yanez-Mo et al., 2015).¹¹

Immune system recognition:

When exosomes derived from one individual enter the body of another individual, they can activate immune responses that lead to their swift clearance or rejection by the recipient's immune system. This phenomenon of immune recognition highlights the significant challenges that arise in the development of exosome-based therapies intended for use across different individuals (Thery et al., 2002).¹² The variability in immune responses among different people complicates therapeutic applications and necessitates careful consideration in the design of such treatments.

Membrane protein differences:

The surface proteins that are found on exosomes play an essential role in facilitating their interactions with target cells. Given that these proteins can vary significantly from one individual to another, the overall functionality and effectiveness of exosomes across different individuals is inherently limited, which can affect their biological roles and potential therapeutic applications (Mathivanan et al., 2010).¹³

Exosomal specificity to microenvironments:

Exosomes are intricately designed to function optimally within the distinct cellular microenvironment of their host. When these exosomes are introduced into a different microenvironment, they may lose their effectiveness or potentially become harmful, which complicates their therapeutic applications even further (Whiteside, 2016).¹⁴

Conclusion

Exosomes play a crucial role in facilitating cellular communication and have significant implications for human health and disease. Their potential applications span a wide range of fields, including regenerative medicine, immune modulation, and targeted drug delivery. However, their involvement in viral transmission underscores the urgent need for further research to fully comprehend their dual nature and implications. Additionally, the unique characteristics of exosomes present substantial challenges for therapeutic applications, as these challenges can vary greatly across different individuals. By gaining deeper insights into these tiny messengers, we could pave the way for groundbreaking advancements in medicine, particularly in combating infections and developing personalized treatment approaches that are tailored to individual needs and conditions. Understanding the full spectrum of exosome functions could ultimately lead to innovative strategies that enhance patient outcomes and improve overall healthcare.

Discussion Point

At the beginning of this piece I postulated that exosomes could challenge the very foundation of person-to-person transmission because they facilitate viral spread from one cell to another within their original host but cannot function in the same manner when removed and placed into another.

Therefore, if exosomes and viral particles, originating in Person A, find their way into Person B, is it not logical to assume the virus will have no affect on Person B? This is because the exosomes will be unable to establish cellular communication within Person B, (non-originating host) resulting in no intercellular viral spread taking place.

No spread - no illness!

This sounds like a topic for another day.

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1. Raposo, G., & Stoorvogel, W. (2013). Extracellular vesicles: Exosomes, micro-vesicles, and friends. Journal of Cell Biology, 200(4), 373-383.

2. Tkach, M., & Thery, C. (2016). Communication by extracellular vesicles: Where we are and where we need to go. Cell, 164(6), 1226-1232.

3. Robbins, P. D., & Morelli, A. E. (2014). Regulation of immune responses by extracellular vesicles. Nature Reviews Immunology, 14(3), 195-208.

4. Lai, R. C., et al. (2013). Exosome therapy: A novel approach for regenerative medicine. Molecular Therapy, 21(7), 1236-1243.

5. Saeedi, S., et al. (2019). Exosome-derived microRNAs: Novel players in neurodegenerative diseases. Frontiers in Neuroscience, 13, 1339.

6. Kalluri, R., & LeBleu, V. S. (2020). The biology, function, and biomedical applications of exosomes. Science, 367(6478), eaau6977.

7. Meckes, D. G., & Raab-Traub, N. (2011). Microvesicles and viral infection. Journal of Virology, 85(24), 12844-12854.

8. Nolte-‘t Hoen, E. N., et al. (2016). Exosomes and viral infections: A double-edged sword. Cellular Microbiology, 18(4), 488-499.

9. Schorey, J. S., et al. (2015). Exosomes and other extracellular vesicles in host-pathogen interactions. Nature Reviews Microbiology, 13(10), 620-630.

10. Mack, M., et al. (2000). Transfer of viral resistance by exosomes derived from T cells. Nature Medicine, 6(7), 769-775.

11. Yanez-Mo, M., et al. (2015). Biological properties of extracellular vesicles and their physiological functions. Journal of Extracellular Vesicles, 4(1), 27066.

12. Thery, C., et al. (2002). Exosomes: Composition, biogenesis, and function. Nature Reviews Immunology, 2(8), 569-579.

13. Mathivanan, S., et al. (2010). Exosomes: Extracellular organelles important in intercellular communication. Journal of Proteomics, 73(10), 1907-1920.

14. Whiteside, T. L. (2016). Exosomes and tumor-mediated immune suppression. Journal of Clinical Investigation, 126(4), 1216-1223.