WHAT ABOUT EXOSOMES IN SKINCARE

The skincare industry is constantly seeking groundbreaking innovations to promise youthful, radiant skin. One of the latest trends is the incorporation of exosomes into skincare products.

Extracellular vesicles (EVs) are small, membrane-bound structures that are released from cells into the surrounding environment. These structures can be categorized as exosomes, microvesicles, or apoptotic vesicles, and they play an essential role in intercellular communication. Exosomes, a subset of EVs, are tiny extracellular vesicles secreted by all cell types. They are praised for their potential to deliver regenerative and anti-aging benefits directly to the skin.

This promise stems from their role in cell-to-cell communication, transporting crucial signaling molecules such as proteins, lipids, and nucleic acids (i.e. mRNA). These molecules can influence various cellular processes, potentially aiding in skin repair, reducing inflammation, and promoting a youthful appearance. However, at the same time, not all signals contained in exosomes are beneficial, some may induce harmful effects and trigger cellular dysfunction. [1]

The popularity of exosomes in clinical settings has recently waned due to issues like poor cargo characterization and short half-life, raising significant concerns about their efficacy and devices. This article aims to delve into the concerns surrounding the use of exosomes in skincare, highlighting the complex manufacturing process, the lack of transparency, and the potential risks involved.

THE COMPLEX PROCESS OF OBTAINING EXOSOMES

Exosomes are not simple to produce. They are obtained through a meticulous process that begins with the culturing of stem cells. These stem cells must be carefully maintained under specific conditions to ensure their health and productivity. Once the cells are sufficiently cultured, the surrounding culture medium is removed. The next steps involve filtering, isolating, and purifying the exosomes from this medium. This series of processes requires a highly regulated and competent Current Good Manufacturing Practice (cGMP) facility, which is essential to maintain the integrity and safety of the exosomes. [2]

 

TRANSPARENCY ISSUES IN EXOSOME SOURCING

One of the most pressing issues with the use of exosomes in skincare products is the lack of transparency from manufacturers. Critical details often remain undisclosed, including:

  • The specific cell lines from which the exosomes were derived.
  • Whether the production facility meets cGMP and ISO certification standards.
  • Documentation on the sterility of exosomes and assurance of low endotoxin levels.

Furthermore, skincare companies frequently do not disclose the stem cell type source of the exosomes. Exosomes could be derived from numerous stem cell types, including embryonic, induced pluripotent, hematopoietic, mesenchymal, neural, and endothelial stem cells. The type of stem cell used can significantly influence the properties and effects of the exosomes, making this information crucial for consumers.

Given that exosomes are derived from biological sources, consumers have a right to know the origin and handling of these materials. Without this information, the safety and efficacy of exosome-based skincare products cannot be guaranteed. This lack of transparency is a significant red flag. [3]

CHARACTERIZATION OF EXOSOME CARGO

A fundamental aspect of exosomes that is often overlooked is the characterization of their cargo. Exosomes carry a diverse array of signaling molecules, including nucleic acids (such as mRNA), proteins, cytokines, and growth factors. These molecules can have profound effects on the recipient cells, which can be either beneficial or detrimental. The effects can range from anti-inflammatory to pro-inflammatory, and from promoting cell growth to inducing cell death (apoptosis).

exosomes

Thus, merely stating that a product contains exosomes is insufficient. The specific content of these exosomes—what they carry inside—is crucial. The impact of exosomes on the skin depends heavily on their molecular cargo. For instance, exosomes with a high concentration of pro-inflammatory cytokines might exacerbate skin conditions rather than improve them. [4][5]

STRESS IN IN VITRO ENVIRONMENTS

The environment in which the exosomes are produced—typically in vitro (outside a living organism)—is often stressful for the cells. This stress may lead to abnormal signaling, resulting in exosomes that carry potentially harmful signals.

  • INCORRECT GAS LEVELS: Inaccurate levels of oxygen (O2) and carbon dioxide (CO2) can disrupt cellular metabolism and function.
  • NUTRIENT AND METABOLIC STRESS: Cells might experience nutrient imbalances or metabolic stress due to suboptimal culture media.
  • OXIDATIVE STRESS: The imbalance between the production of reactive oxygen species (ROS) and the cell's ability to detoxify these harmful products can lead to cellular damage and altered signaling.

For example, stressed cells may secrete exosomes with higher levels of pro-inflammatory cytokines, which could potentially worsen skin conditions instead of improving them. This amplification of harmful signals within exosomes highlights the importance of maintaining optimal culture conditions to ensure the production of beneficial exosomes. [6]

POTENTIAL NEGATIVE EFFECTS

The amplification of harmful signals within exosomes can lead to a predominance of pro-inflammatory signals, worsening skin conditions. While exosomes have the allure of targeted delivery with lower immunogenicity compared to stem cell therapies, their potential hinges on two critical factors:

  • Comprehensive characterization of exosome cargo.
  • Optimal culture conditions in an experienced cGMP lab.

Exosomes could benefit various skin conditions, but this remains speculative without clear clinical evidence, which is currently sparse. A full characterization of cargo, cell type, and other factors is essential and often not provided by skincare companies selling exosome creams. Using biologically active exosomes with unknown sources or compositions is a risk. Addressing large-scale manufacturing, purification, batch-to-batch variation, and complex cargo analysis is necessary for clinical translation. [6][7]

CONCLUSION

The promise of exosomes in skincare is marred by substantial unknowns and potential risks. Without rigorous transparency from companies about their sourcing, production standards, and detailed characterization of exosome cargo, consumers cannot be assured of the safety or effectiveness of these products. While exosomes hold some hope due to their lower immunogenicity compared to stem cell therapies, the current state of knowledge and practice in the industry is insufficient to guarantee their benefits. Until these gaps are addressed, the use of exosomes in skincare remains a venture fraught with uncertainty.

In summary, the skincare industry must prioritize scientific integrity, transparency, and rigorous testing to harness the potential of exosomes. Until then, consumers should approach exosome-based skincare products with caution, demanding clear and comprehensive information about their production and content.

REFERENCES:

[1] A review of the regulatory mechanisms of extracellular vesicles-mediated intercellular communication, Ya-Juan Liu &  Cheng Wang - Cell Communication and Signaling volume 21, Article number: 77 (2023) 

https://biosignaling.biomedcentral.com/articles/10.1186/s12964-023-01103-6#auth-Ya_Juan-Liu-Aff1

[2] Manufacturing Therapeutic Exosomes: from Bench to Industry, So-Hee Ahn,1,3 Seung-Wook Ryu,1,3 Hojun Choi,1 Sangmin You,1 Jun Park

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9095511/

[3] Andreu Z., Rivas E., Sanguino-Pascual A., Lamana A., Marazuela M., González-Alvaro I., Sánchez-Madrid F., de la Fuente H., Yáñez-Mó M. Comparative analysis of EV isolation procedures for miRNAs detection in serum samples. J. Extracell. Vesicles. 2016;5:31655. doi: 10.3402/jev.v5.31655

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4916259/

[4] Bachurski D., Schuldner M., Nguyen P.H., Malz A., Reiners K.S., Grenzi P.C., Babatz F., Schauss A.C., Hansen H.P., Hallek M., et al. Extracellular vesicle measurements with nanoparticle tracking analysis - an accuracy and repeatability comparison between NanoSight NS300 and ZetaView. J. Extracell. Vesicles. 2019;8:1596016. doi: 10.1080/20013078.2019.1596016

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6450530/

[5] Battistelli M., Falcieri E. Apoptotic bodies: particular extracellular vesicles involved in intercellular communication. Biology (Basel) 2020;9:21. doi: 10.3390/biology9010021

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168913/

[6] Friends and foes: Extracellular vesicles in aging and rejuvenation, Brian V. Lananna and Shin‐ichiro Imai

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8493967/

[7] Environmental Exposures and Extracellular Vesicles: Indicators of Systemic Effects and Human Disease, Christina M. Eckhardt, MD, Andrea A. Baccarelli, MD, PhD, and Haotian Wu, PhD

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9395256/