Exosomes are membrane-bound extracellular vesicles with a size of 30–150 nm, secreted by nearly all cell types. They were originally considered cellular waste products, but it is now established that they play an essential role in intercellular communication. They transport proteins, lipids, and RNA and regulate numerous physiological processes, including immune responses, tissue regeneration, and metabolic regulation.
Due to their versatile functions, exosomes are increasingly coming into focus in biomedical research, particularly regarding their potential application in regenerative medicine, diagnostics, and targeted drug delivery, including in dietary supplements. In this article, we will discuss the functioning of exosomes and take a closer look at their opportunities and possibilities.
Biogenesis and function of exosomes
Exosomes are formed within the cell through a specific sequence of intracellular processes:
Formation of multivesicular endosomes (MVEs)
In our cells, there are small "factories" called endosomes. In these endosomes, even smaller "packages" called exosomes are formed. You can imagine it like pressing an air bubble, creating a new, small bubble inside.
There are two ways in which these exosomes are formed:
- With the help of a "sorting team": A complex system of proteins called ESCRT helps to shape the exosomes properly.
- In other, still unknown ways: There are also mechanisms that function independently of ESCRT - these are not yet fully understood.
When the endosome is full of these small exosome packets, we call it a multivesicular endosome (MVE). Imagine the MVE is like a bag full of small messages. This bag then fuses with the cell membrane and opens outward, releasing the exosomes. These exosomes then float around the body and deliver messages to other cells as signaling molecules.
Exocytosis of the exosomes
The MVEs (the "bags" full of exosomes) fuse with the cell membrane and thereby release the exosomes into the space outside the cell.
Interaction with target cells
Exosomes are small packages with important information. When they dock to or are taken up by other cells, they release their molecular content.This content can change the function of the cell by triggering specific signaling pathways or leading to changes in the tissue. The exosomes act like small regulators of cell activity.
Regulation by microRNAs (miRNAs)
Exosomes transport a variety of microRNAs that can specifically penetrate target cells and regulate gene expression there. These miRNAs can either inhibit or stimulate the production of certain proteins. (Learn more about this in the article on proteomics) This has significant implications for cellular processes such as inflammation, tissue regeneration, and cell protection.
For example, certain miRNAs in exosomes have been shown to be capable of suppressing inflammatory signaling pathways and activating repair mechanisms in damaged tissues.In cancer research, it is being investigated how exosomal miRNAs influence tumor progression and whether they can be used as a targeted therapy option.
Comparison of plant and human exosomes
Both animal and plant cells produce exosomes, but they differ in their molecular composition and potential applications:
|
Property |
Human exosomes |
Plant exosomes |
|
Origin |
Stem cells, immune cells, epithelial cells |
Plant cells (fruits, vegetables, herbs) |
|
Function |
Immune modulation, tissue regeneration, signal transduction |
Antioxidative, anti-inflammatory properties |
|
Composition |
Proteins, microRNAs, lipids |
Polyphenols, plant RNA |
|
Stability |
Relatively unstable in the digestive tract |
High stability and bioavailability |
While human exosomes are being researched for personalized therapies, plant exosomes have great potential as natural dietary supplements.Studies show that they may have anti-inflammatory effects and may influence the intestinal microbiome. Plant exosomes from grapes or broccoli contain bioactive molecules that could act as prebiotic substances.
Potential of exosomes for longevity and obstacles to implementation
Exosomes could also play a very important role in longevity research due to the properties described above, particularly in the following areas:
- Cellular senescence: Cellular senescence refers to a state in which cells irreversibly withdraw from the cell cycle. Exosomes could contribute to the elimination or reactivation of senescent cells, thereby slowing down the aging process.
- Mitochondrial Function: Exosomes could specifically correct mitochondrial dysfunctions that play a key role in age-related diseases.
- Immune Regulation: By modulating the immune system, exosomes could inhibit chronic inflammatory processes that contribute to age-related diseases.
- Neurodegenerative Diseases: Exosomes show promising approaches in the treatment of Alzheimer’s and Parkinson’s, as they could promote neuronal regeneration.
Learn more about the molecular foundations of the aging process at the Hallmarks of Aging.
Why are exosomes not yet used more widely?
Despite their enormous potential, there are several challenges that currently limit the widespread application of exosomes in longevity medicine:
- Lack of standardization: The production and characterization of exosomes is complex and requires standardized protocols that have not yet been fully established.
- Regulatory hurdles: The legal classification of exosomes as drugs or dietary supplements is unclear, making market entry difficult. Additionally, non-plant exosome therapies are currently not approved within the EU.
- Insufficient clinical studies: Many studies are still in the preclinical stage, and long-term data on safety and efficacy are lacking.
- Ethical questions: Especially with exosomes from human stem cells, there are ethical concerns regarding their extraction and application.
Despite these challenges, ongoing research on exosomes will lead them to play a key role in longevity research and personalized medicine in the coming years. Advances in biotechnology, optimized manufacturing processes, and regulatory clarity are likely to pave the way for this.
Regulatory framework for exosomes in the EU
The legal classification of exosomes varies depending on the area of application:
- Medicinal products: Human exosomes are subject to the Advanced Therapy Medicinal Products (ATMPs) regulation of the EMA and require comprehensive clinical testing.
- Dietary supplements: Plant-based exosomes may fall under the Novel Food Regulation (EU Regulation 2015/2283) if they represent a novel ingredient.
- Cosmetic products: Exosome-based skincare must comply with the EU Cosmetics Regulation (EC) 1223/2009, with corresponding studies on safety and efficacy.
Exosomes in already existing products and markets
Exosomes are already commercially available in various industries and have established themselves in certain areas:
Cosmetic applications
Exosome-containing skincare products are marketed by various brands as an anti-aging solution. These products contain exosomes that are said to stimulate collagen production and support skin regeneration. Some dermatological treatments also use exosomes to accelerate skin rejuvenation and wound healing.
Regenerative medicine
In clinical studies, exosomes are being investigated for promoting tissue regeneration.Initial applications show promising results in the treatment of cartilage defects and muscle injuries. Certain companies offer exosome-based injections for regenerative orthopedics and aesthetics.
Hair growth therapies
Exosomes are increasingly used in hair care products and scalp treatments, with the intention of promoting hair growth and reducing hair loss. Clinical applications combine exosomes with PRP (Platelet-Rich Plasma) to stimulate the regeneration of hair follicles.
Functional foods and dietary supplements
Plant-based exosomes from foods like grapes and ginger are used in dietary supplements to provide antioxidant and anti-inflammatory benefits.Some companies are developing exosome-rich foods to support the microbiome and improve gut health.
For example, exosomes from ginger are used in functional beverages and dietary supplements, as they can transport anti-inflammatory agents that are particularly beneficial for people with gastrointestinal issues.
Drug development and active ingredient transport:
Pharmaceutical companies are researching exosomes as carriers for targeted drug delivery. Initial trials show that exosomes can transport active ingredients precisely to diseased tissues. Especially in oncology, exosomes are being investigated as vehicles for targeted drug delivery.
Advantages of exosomal applications
- Highly efficient cell communication: Exosomes transmit biological signals specifically to target cells.
- High bioavailability: Plant exosomes are stable against digestive enzymes and reach the organism intact.
- Regenerative potentials: Accelerated wound healing and tissue repair are attributed to exosomes.
- Wide range of applications: Medicine, cosmetics, and functional nutrition could significantly benefit from exosomes.
- Targeted Active Ingredient Delivery: Exosomes offer a means for targeted therapies through the transport of bioactive molecules.
Challenges and Open Questions
Despite the promising potential of exosomes, there are still some hurdles that complicate widespread application. There is a lack of long-term studies on safety and efficacy, which complicates clinical approval. Additionally, regulatory requirements are inconsistent, as exosomes could be classified as drugs, dietary supplements, or cosmetic active ingredients depending on the area of application. Depending on whether patenting is possible, there are more or less incentives from private entities to invest significant money in research.
The production is also demanding: The isolation, purification, and scaling require complex biotechnological processes that currently incur high costs. Furthermore, there are immunological risks, as exosomes can potentially trigger unexpected reactions in the immune system.
When using human exosomes, there are also ethical concerns, especially when they are derived from stem cells. Standardization of manufacturing processes and further research are necessary to establish exosomes as a safe and effective therapeutic tool.
Future Perspectives of Exosome Research
Exosomes are more than just cell fragments – they represent a highly developed platform for cellular signal transduction and intercellular substance transport.While plant-based exosomes are already being researched in functional nutrition, human exosomal applications face regulatory and technological challenges. Ongoing research will help advance exosomes as an innovative therapeutic option for regenerative medicine, targeted drug delivery, and personalized medicine.
