Unless you have been hiding under a rock for the last 12 months, one of the hottest and most controversial topics in aesthetics has been the use of exosomes. I have been researching the market since 2019 with the intention of introducing an exosome product as a distributor, and I have spoken with companies from several countries offering differing sources of exosomes.
As well as the source difference, I was offered many ranges of exosome quantity per vial as manufacturers adopted a ‘mine is bigger than theirs’ approach to this relatively new field.
Then, having spoken with the US scientists behind EXO|E, I settled on their Plant Extracellular Nanoparticle technology (PEN). There were a number of advantages of this technology. PENs are the plant version of exosomes, and EXO|E contains a high concentration of these in its product, along with other important factors that I felt give it the edge.
First, let’s look at exosomes: what are they, and how do they work?
What are exosomes?
Exosomes are microscopic vesicles ranging from 30-150 nanometres and are essential communication messengers. Once introduced to the target tissue, these tiny vesicles initiate cell-to-cell communication and deliver bioactive molecules that promote cellular regeneration and rejuvenation.
Exosomes can carry a diverse load of molecules, including microRNAs and mRNAs, interleukins, cytokines and lipids. Exosomes interact with recipient cells by binding to their surface receptors, which enables the internalisation of exosomes into the target cells; the exosome molecular load is then released and begins to exert its effects. Exosomes are derived from many sources, and practitioners should be aware of the origin of the product they are using. Currently, in the UK and the EU, exosomes derived from human sources are not allowed to be used due to directive 2004/23/EC, which states, “In view of the risk of transmission of communicable diseases, the use of human cells, tissues and products is prohibited.” This means injectable and topical application of exosomes derived from a human source is prohibited. There can be no off-label use by prescribers either, as the products are not licensed for any use. This was a significant reason I opted against human-derived exosome products. As well as legality, other important factors influenced my decision.
Other sources of exosome products available in the UK include animal (mammal), fish and plant, which are all legally available. Mammal and fish-derived exosomes all still contain trace elements of the DNA of the donor, and several religions and lifestyle choice groups would not welcome their use on themselves.
Mammal, fish, and human-derived exosomes are all supplied as a lyophilised product that needs reconstitution before use. Lyophilising or freeze-drying denatures the proteins of a product. Try powdered milk! The denaturing of the proteins means the manufacturers must add back into the product synthetic growth factors, and the number that they add is typically between five to 20 – significantly reducing their effectiveness when compared with a product that has thousands of active growth factors in their natural state, such as EXO|E.
Mammalian and fish-derived exosomes also need help to get through the epidermal barrier. Despite only having licenses for topical application, they require either injection on needling into the skin or application post ablative procedure in order to attempt to get them where they need to be to have any effect, which to me was again a limiting factor in the marketability of such a product. When I discovered EXO|E, I discovered a product that is applied topically and can pass through the epidermal barrier.
What attracted me to EXO|E?
EXO|E is a consortia of plant stem cell extracts containing PDENS (plant exosomes) and other secretary cell factors derived from vegan sources.1-4 EXO|E is lipophilic, so it is applied topically to the skin and is not injected.
While I was focused on the quantity of exosomes in the product (because more is better, right?), Dr Rob King, from the manufacturer, explained to me that it isn’t just about the exosomes.
Exosomes are communication vesicles; increasing the quantity increases communication, but if you just take exosomes from any source, you don’t know what they are communicating and what they are carrying. Sure, they may improve certain outcomes just by increasing messaging, but with EXO|E in production, they actually induce an inflammatory environment that the plant stem cells are in and then extract the full composition of secretary factors released by the stem cells as they appropriately react to the inflammation. This extraction contains exosomes (there are 25 billion over the entire 15-day EXO|E course), liposomes, growth factors, interleukins and cytokines – all focus on reducing inflammation and repairing the damaged cells. So, in effect, these are targeted, programmed nanoparticles to reduce inflammation and promote wound healing. My mind was blown!
So why use exosomes with in-clinic treatments?
The four phases of wound healing are:
- Haemostasis
- Inflammation
- Proliferative
- Remodelling.5-6
The first phase is haemostasis. Haemostasis is the process of the wound being closed by clotting. It prevents blood loss, starts immediately after injury and lasts only five to 10 minutes. Platelets in the blood gather to stop bleeding by forming a clot. These platelets recruit a host of cells to come to the site of injury by secreting chemical signals. This results in a transition to the second phase, the inflammatory phase, which lasts four to six days and is characterised by the presence of erythema, warmth, oedema, and pain.7-8 Stem cells, fibroblasts, endothelial cells, macrophages, and other cells are also called up to repair and regenerate the damaged tissues and transition to the 3rd phase of wound healing over the next six to 21 days. In this proliferative phase, new collagen and blood vessels are formed, healing and strengthening the damaged tissues. The fourth and final phase in wound healing is remodelling, also known as the maturation phase. From 21 days up to two years, the collagen fibres are thickened and strengthened.9-12
Skin rejuvenation treatment devices used in clinics aim to induce a targeted, measured, limited and clean injury to the skin to induce new collagen production and remodelling. This intentional skin injury results in inflammation that leaves the skin red, swollen, and tender, resulting in patient discomfort, a potentially lengthy recovery time of one to 12 weeks, and a patient experience that may deter them from completing the recommended number of treatments for optimal results.8
All clinics will have seen patients surprised by the pain during treatment and unable to cope with the downtime the treatment caused.
EXO|E helps deliver rapid relief of symptoms that may be caused by any inflammatory process and helps generate noticeable tissue enhancement.
EXO|E works to minimise the Inflammatory 2nd Phase and quickly transition the targeted tissues to optimise the desired Proliferative 3rd Phase. The whole, balanced, and natural combination of exosomes, soluble factors, and other secretory factors derived from plant and yeast cells is a novel approach to wound healing and regenerative medicine. 10, 11
EXO|E’s powerful anti-inflammatory effect is produced through patented biotechnology to minimise inflammation, redness, swelling, pain, and discomfort induced during the 2nd phase and optimise the aim of the 3rd phase in which new collagen, elastin, blood vessels, hyaluronic acid is formed to renew, plump, moisturise and rejuvenate skin tissues.
This enhancement of the proliferative phase results in a clinically visible and tangible improvement of the treated tissues as well as providing a superior patient experience with much less discomfort, shortened recovery time, and much more likelihood of patient compliance and desire to return and complete the course of treatments that may be required to achieve the desired clinical result.
Advantages of using vegan cell sources to produce the EXO|E product include: The exosomes and other secretory factors produce the desired action of the tissues using a universal cellular language; Being able to reproduce the same product consistently and routinely; Being free of potential pathogens, such as viruses and prions, that may be transmitted by products derived from human or animal sources.
EXO|E also does not have a single application approach, as used by the other products, where they are applied after an invasive treatment. The EXO|E treatment course is delivered over 15 days with 29 applications during this period. This is because secretary signals between cells have a paracrine effect, like how hormones in the blood have an endocrine effect.
These signals bind to cell receptors, and once the receptors are saturated, they have reached their limit to exert further effect. At this point, the paracrine response is either maxed out, or an opposite response to counteract and reduce this signal is caused. In order to avoid the downregulation of the desired paracrine signals and to maximise the effect on the dynamic intracellular interaction, EXO|E is designed to deliver over 25 Billion nanoparticles over the 15-day course of treatment to maintain and direct the desired anti-inflammatory effect and enhance the regenerative proliferative phase.
The EXO|E treatment kits comes in three parts.
Step 1
EXO|E’s pre-treatment product D|TOX is applied topically at home for seven days prior to the treatment by the patient morning and night. D|TOX stimulates cell autophagy, which clears up cellular debris, leaving healthy cells as well as increasing the body’s own production of hyaluronic acid resulting in better hydrated healthy cells, preparing the skin for treatment.
Step 2
EXO|E in clinic application. EXO|E is applied topically prior to any treatment. If using topical anaesthetic, EXO|E is applied 10 minutes prior to the anaesthetic and allowed to absorb. EXO|E in-clinic application contains over 15 billion nanoparticles and enhances the patient’s overall in-clinic experience by minimising redness and inflammation. Each application is shown to reduce inflammation by 61%. By reducing the patient’s background inflammation prior to treatment, the lower inflammation starting point will mean a lower peak of inflammation following the treatment – reducing patient risk and potential negative outcomes. The powerful natural formulation also helps to stimulate hydration, collagen, elastin and hyaluronic acid production.
Step 3
EXO|E’s post-treatment product RE|PAIR is applied topically at home for seven days post procedures morning and night. RE|PAIR helps control and reduce inflammation healing time and increase cell proliferation and hydration. It also helps to stimulate collagen, elastin and hyaluronic acid production for brighter, healthier skin.
The EXO|E regimen also includes a continual care regime where D|TOX serum can be applied at home by the patient daily in the morning to continue the autophagy effect on the cells and continue to stimulate cellular debris clean-up and promoting the production of hyaluronic acid and the RE|PAIR is applied daily at night for the reduction in inflammation and continued collagen and elastin benefits. The continual care regime contains a lower concentration of PDENs, with five billion being contained in each 30ml bottle.
New in the UK are the DE|RIVE PDEN hair and scalp support products. DE|RIVE comes in a two-part kit:
A super concentrated syringe of over 15 billion nanoparticles specially formulated with plant-based biomimetic stem cell extracts for scalp and hair health.
A lower concentration home care serum for twice daily application to nourish the scalp and hair follicles, continuing the removal of dead skin cells and stimulating hydration and blood flow to the scalp.
DE|RIVE is applied topically in clinic and can also be micro-needled into the scalp or applied with the AquafirmeXS ULTRA technology to painlessly enhance delivery to the deeper follicles of the scalp and also provide ultrasonic stimulation of hair follicles. DE|RIVE is shown in studies to increase cytokeratin 15 protein levels, which are integral to the fortification of the hair shaft itself. Utilising the ULTRA technology in clinic and the DE|RIVE homecare, results can be seen as quickly as 30 days. A course of four treatments over six months is recommended.
The EXO|E technology, as well as the pipeline of plant-derived nanotechnology, excited me then and having seen it in action in many clinics now in the UK, including on my own face and scalp, is keeping me excited as we are taking aesthetic treatments to a different level of results whilst enhancing the patient experience in clinic and considerably reducing their post-procedure downtime.
Resources
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2. Teng Y, Xu F, Zhang X, et al. Plant-derived exosomal microRNAs inhibit lung inflammation induced by exosomes SARS-CoV-2 Nsp12. Mol Ther. 2021;29(8):2424-2440. doi:10.1016/j.ymthe.2021.05.005
3. Cui Y, Gao J, He Y, Jiang L. Plant extracellular vesicles. Protoplasma. 2020;257(1):3-12. doi:10.1007/s00709-019-01435-6
4. Dad HA, Gu TW, Zhu AQ, Huang LQ, Peng LH. Plant Exosome-like Nanovesicles: Emerging Therapeutics and Drug Delivery Nanoplatforms. Mol Ther. 2021;29(1):13-31. doi:10.1016/j.ymthe.2020.11.030
5. Hoyle NP, Seinkmaine E, Putker M, et al., Circadian actin dynamics drive rhythmic fibroblast mobilization during wound healing. Sci Transl Med. 2017;9(415):eaal2774. doi:10.1126/scitranslmed.aal2774.
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7. . Liu T, Zhang L, Joo D, Sun SC. NF-κB signalling in inflammation. Signal Transduct Target Ther. 2017;2(April). doi:10.1038/sigtrans.2017.234. 7.
8. Dinarello CA. Overview of the IL-1 family in innate inflammation and acquired immunity. Immunol Rev. 2018;281(1):8-27. doi:10.1111/imr.12621
9. McCance KL, Huether SE, Geneser F, et al. Collagen Structure and Stability. PLoS One. 2010;78(3):929-958. doi:10.1146/annurev.biochem.77.032207.120833.COLLAGEN
10. Tahergorabi Z, Khazaei M. A review on angiogenesis and its assays. Iran J Basic Med Sci. 2012;15(6):1110-1126.
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