Exosome Treatments

What are exosome treatments?

Exosome treatments involve delivering products derived from extracellular vesicles released by cells to the skin or scalp. These vesicles are very small particles enclosed in a double-layered lipid (fat) membrane. They carry proteins, lipids and nucleic acids and mediate communication between cells. In aesthetic medicine, they are being studied for skin renewal, hair, scars and pigmentation (skin colour).

Studies report that these particles can affect inflammation in the skin, the formation of blood vessels, the remodelling of the extracellular matrix (the support structure that surrounds cells), pigmentation and the hair cycle. However, much of this information comes from laboratory and animal studies. A systematic review on facial rejuvenation, which gathered studies using set rules and assessed them together, also still treats effects such as stimulating collagen production and regulating inflammation as proposed effects. In other words, it is not yet clear how, and to what extent, exosomes work in humans.

Exosomes are not living cells. For this reason, they are regarded as a cell-free approach and are kept separate from stem cell treatments. Although the source may be a cell culture, what you receive is not the cell itself but a product containing the particles that the cell releases. The content of the product varies according to its source and how it is made.

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What does ‘exosome’ mean?

‘Exosome’ is the name of one subtype of extracellular vesicle. In its strict sense, the word describes small vesicles that originate from a specific transport route inside the cell (the endosomal pathway). In aesthetic publications and product promotion, however, it is used much more broadly, for almost any product said to contain extracellular vesicles.

Researchers who have looked at its use in aesthetic and regenerative medicine (the field of medicine that aims to repair and renew tissues) point out that many products and studies call these preparations exosomes, but that this specific origin of the particles is not always demonstrated. For this reason, some publications in this field prefer the broader terms ‘extracellular vesicle’ and ‘small extracellular vesicle’.

In its current guidelines, the International Society for Extracellular Vesicles, the field's international scientific society, also lists several challenges that are still being worked on: correct naming, telling vesicles apart from non-vesicular particles, and describing the properties of these particles (characterisation). In practical terms, this means that the word ‘exosome’ on a product does not, on its own, tell you what is in it or how much of it there is.

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Where do exosomes come from?

Most exosome products used for aesthetic purposes are derived from cultures of mesenchymal stem cells (stem cells originating from connective tissue); platelets, immune cells or plants can also be used as sources. Human studies in dermatology likewise show that the source is mostly mesenchymal stem cells.

In studies on hair loss, mesenchymal stem cells have been obtained from various tissues, such as fat tissue, the placenta, hair follicles, bone marrow, foreskin and the umbilical cord; products prepared from plant extracts have also been tried. According to researchers, the range of sources extends from mesenchymal stem cells to immune cells and platelets, and each source gives the product a different molecular signature — in other words, its own distinctive content. That is why the first question to ask, to understand what a product is, is where it comes from.

Plant-derived vesicles are a separate matter. The evidence for their use in dermatology remains largely at the laboratory level; clinical data are limited, and the methods used to obtain and characterise these particles vary from study to study. The fact that a product is plant-based does not, on its own, tell you anything about its effectiveness or safety.

The way the product is given also varies. In studies, products have been applied to the skin surface, delivered by microneedling (creating tiny channels in the skin with very fine needles), applied after fractional CO2 laser treatment or given by injection.

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What do studies on facial skin show?

Most studies on facial skin report improvements in skin quality measures such as wrinkles, pigmentation, moisture and elasticity; however, the certainty of this evidence is low or very low. A systematic review of extracellular vesicle treatments for facial rejuvenation assessed 16 studies with a total of 503 participants.

Most of these studies found improvement in at least one skin quality measure, and in comparative studies the results generally favoured the side treated with vesicles. On the other hand, the risk of bias (the likelihood that the result was influenced by the study's design) was rated moderate to critical for most of the efficacy results, and the certainty of the evidence was graded low or very low. The researchers consider that no firm conclusion can be drawn because of methodological limitations, inconsistent measurements and short follow-up.

Individual studies fit this picture. In a randomised study of 28 people (the side of the face that received each treatment was chosen at random), a solution containing exosomes derived from fat-tissue stem cells was applied to one half of the face with microneedling, and saline was applied to the other half, also with microneedling; at the final follow-up visit, more marked improvement was reported on the exosome side. In a 60-person split-face study (one side of the face compared with the other) in which a vesicle product was added after radiofrequency (RF) microneedling, follow-up lasted 12 weeks and the study was not blinded, meaning the treatment given was not kept hidden; the researchers state that the results should be interpreted with caution. In a split-face study that compared exosomes with platelet-rich plasma (PRP) using the same method, and in which the assessor did not know which side had received which treatment, both sides showed similar improvement in wrinkles, uneven skin tone, redness and skin texture.

In many of these studies, exosomes were not given on their own but together with another procedure, such as microneedling. Whether it is possible to say how much of the observed change is due to the exosomes depends on whether the same procedure was also carried out on the comparison side. There is even less evidence on scars and pigmentation: a systematic review of the effects of mesenchymal stem cell-derived exosomes on scars, ageing and dark patches (hyperpigmentation) is based on 6 studies with a total of 99 people and regards the evidence as being at the level of preliminary findings. In another review of exosome use with microneedling, 8 studies could be included in the final assessment, and the number of participants in these studies ranged from 3 to 60.

RELATEDPRP

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Where does the evidence stand for hair loss?

Exosome studies in hair loss show a promising but limited picture; effectiveness and safety have not yet been established. A systematic review of the clinical evidence across different types of hair loss covers 11 studies:

• 2 randomised controlled trials.
• 3 retrospective studies (based on past patient records).
• 3 prospective studies with no control group.
• 1 case series (a publication describing several patients together).
• 2 case reports (publications describing a single patient).

All of these studies reported improvement in at least one hair measure, and no serious side effects were reported. However, because the study designs differ from one another, it is difficult to compare the results directly; participant numbers are small and follow-up periods vary. The researchers state that better-quality randomised trials are needed before standard treatment protocols can be established.

Another review that critically assessed regenerative treatments for androgenetic alopecia (male- or female-pattern hair loss, the most common type, linked to hormones and genetics) also found the clinical evidence on stem cell and exosome treatments promising but still limited; it stresses that standardised methods are key to transparency, reproducibility and patient safety. Hair loss is not a single condition, and research looks at its different types separately. The type of hair loss you have is determined at a consultation.

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Limits of this treatment

The current limits of exosome treatments come from the evidence: studies are small, follow-up periods are short, and most designs do not include a comparison group. The long-term effects and safety are not known. A review of 17 human studies in dermatology listed small participant groups, short follow-up, non-randomised single-group designs and possible conflicts of interest among the limitations.

Another systematic review, of 19 human studies on skin renewal, also found that most of the studies were not randomised and that the effects were observed over the short term. According to the review of exosome use with microneedling, larger studies with longer follow-up are needed to establish safety and effectiveness. A meta-analysis (an analysis that statistically combines the results of different studies) that pooled 39 human studies in aesthetics reports consistent findings in the direction of improvement; however, it also acknowledges that differences between the studies and non-standardised protocols limit how far these results can be generalised. That is why the pooled percentages from the analysis should be viewed with caution: reducing results from different products, doses and methods to a single number creates an impression of certainty that the data do not support.

In concrete terms, this means that the outcomes measured in studies are things like wrinkles, pigmentation, moisture, elasticity, pore appearance and hair density; lifting sagging skin or restoring lost volume is not the aim of these studies. Repair effects shown in the laboratory are not proof that the same will happen in people. For this reason, exosome treatment cannot be presented as a promise that tissue will be renewed.

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Why do products differ?

The content of exosome products is not fixed or uniform. The source cells and the manufacturing and purification methods change the product, and there is no agreed standard for quality or effectiveness. Researchers who have examined their use in aesthetic and regenerative medicine also note that, because of differences in biological source and in isolation and application methods, studies in this field remain very different from one another.

Another assessment of their use in dermatology lists the main limitations as follows:

• Low production yield.
• Differences between products and their contents.
• No agreed standards for quality and effectiveness.
• Uncertain regulatory status (the product's position in terms of official approval and oversight).

Whether these treatments become part of standard treatment is also seen as depending on consistent manufacturing, shared standards for describing product content, meaningful tests of effectiveness, and comparative studies that follow results for years rather than weeks.

The regulatory picture is similar. A review of the regulation of exosomes as biological medicines highlights three points: the variety of manufacturing techniques makes standardisation difficult, regulatory approaches vary from country to country, and a therapeutic exosome product should be approved only after its molecular structure, its behaviour in the body and its effectiveness have been demonstrated. In its position paper on clinical studies, the International Society for Extracellular Vesicles also stresses that whether vesicles are regarded as the active substance or as a carrier determines the requirements for manufacturing, quality control and clinical research.

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Regulatory warnings

The US Food and Drug Administration (FDA) has announced that there are no approved exosome products in the US, and it has warned the public following reports of serious side effects involving unapproved products. These warnings apply to the US and do not indicate a product's status in Türkiye; however, they clearly reveal the regulatory uncertainty in this field.

According to the FDA's Public Safety Notification of December 2019, serious side effects were reported in patients in the state of Nebraska who had been treated with unapproved products marketed with the claim that they contained exosomes. The same notification also states that exosomes used to treat diseases and conditions in humans are generally regulated as drugs and biological products and require review and approval before they are marketed. The agency's 2020 Consumer Alert repeats that misleading information about these products is widespread online and that there is no approved exosome product.

Publications from other countries paint a similar picture. A case series states that the exosome-containing cosmetic products it looked at were approved for use on the skin surface, but that injecting them into the skin is an unregulated, off-label use (outside the uses covered by the product's licence or approval) in many countries, including South Korea. A case report also emphasises that there is no exosome product approved for injection into the skin. This is why you need to ask separately, for each product suggested to you, about its registration status in Türkiye and the manufacturer's intended purpose — that is, whether it was made to be applied to the skin surface or to be injected.

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Known risks

Side effects reported in controlled studies are mostly mild and temporary. However, serious complications such as tissue death (necrosis), granuloma (an inflammatory lump of tissue that the body forms in reaction to a foreign substance) and permanent scarring have been reported in individual cases, particularly after injection into the skin. Long-term safety data are not yet available.

No serious side effects were reported in the studies included in the facial rejuvenation review; however, the researchers see this only as a positive safety signal for the short term and state that the short follow-up does not allow a firm conclusion. In the split-face study combined with radiofrequency (RF) microneedling, local reactions at the treatment site were temporary and mostly mild. According to another review of human studies, the safety profile of treatments applied to the skin surface is favourable in most studies; for off-label use by injection, however, there are individual reports of risks.

Studies in dermatology include rare reports of granuloma, necrosis and allergic reactions after injection. One case report describes a patient who was given freeze-dried exosomes for acne scars through multiple injections into the skin of the cheeks. Three days later, the patient developed tissue death attributed to impaired blood circulation, with painful, open (ulcerated) raised lesions and dark discolouration; this ultimately left marked depressed scars and darkening of the skin. In a case series of four patients who had unapproved products injected into the skin outside clinical settings, the patients developed long-lasting redness, nodules (firm lumps in the skin), granulomatous inflammation and scarring. Despite treatment, none of the cases fully resolved.

These reports are based on individual cases and do not show how often these complications occur. However, the fact that they are limited to individual cases does not mean the risk can be ignored. That is why it is important to ask, before the treatment, about the product's source, its approval status and how it will be given. These risks must be explained to you before the treatment.

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