Exosomes: the new frontier in aesthetic medicine?

In the realm of aesthetic and regenerative medicine, a potentially revolutionary new approach is gaining traction: exosome therapy.

While research is still in its infancy, exosome therapy is emerging as a promising contender in a range of therapeutic applications, such as tissue regeneration, wound healing and the treatment of various diseases, including neurological disorders and cardiovascular and autoimmune diseases.

Exosomes hold incredible potential for personalised medicine, given their specificity for certain tissues and disease states. They can serve as personalised diagnostic biomarkers and as advantageous drug delivery systems – one of their most notable advantages is their ability to cross biological barriers,¹ including the blood-brain barrier.

Their small size, low toxicity and high biocompatibility make exosomes particualrly attractive for therapeutic applications, including those in aesthetic medicine.²

Indeed, the role of exosomes is garnering significant interest in the field of aesthetic medicine. These tiny extracellular vesicles are gaining recognition for their unique ability to facilitate intercellular communication, which can be used in tissue regeneration and repair and overall skin health and rejuvenation.

Understanding exosomes

Exosomes are tiny vesicles released by cells in the body into the extracellular environment. They are defined as nanosized particles, ranging from 30 to 150nm in diameter, and are enclosed by a lipid bilayer. They are secreted by nearly all types of cells and contain a diverse array of components such as proteins, nucleic acids, lipids and genetic material (RNA and DNA).

‘What’s interesting about exosomes is that they can be released by almost all types of cells in the body, including those in our organs, tissues and even our bloodstream,’ Dr Tunc Tiryaki, a London-based plastic surgeon, told Aesthetic Medicine (UK)³. ‘They play a role in cell-to-cell communication, allowing cells to send signals and exchange information with each other over short and long distances. Research has shown that exosomes promote tissue repair, stimulate angiogenesis and modulate inflammation, suggesting their therapeutic potential for treating various diseases and injuries.’

Exosomes themselves are not cells and are incapable of reproduction. Their main role is in intercellular communication, transporting signals and information from one cell to another. Exosomes are natural carriers of bioactive molecules, and their contents and composition vary depending on the type of cell from which they were derived.

Exosomes are derived from various cell types – including human adipose-derived mesenchymal stem cells (MSCs), umbilical cord MSCs, bone marrow MSCs, as well as derived from bacteria and plants – and their cargo reflects the characteristics of the parent cell. When introduced into the body, exosomes can interact with target cells, delivering their cargo and altering cellular functions. Through these interactions, exosomes can alter the pathophysiological conditions of recipient cells, impacting processes involved in cell growth, tissue repair and collagen synthesis. Simply put, it is thought that when a healthy cell sends an exosome to an unhealthy cell, the damaged cell begins to repair and regenerate itself.

Exosomes and their role in aesthetic medicine

First identified in 1983, exosomes are currently being extensively studied for their role in various biological and pathological processes.

In aesthetic medicine, exosomes are being examined for their anti-inflammatory properties and skin repair and regeneration capabilities alongside their favourable characteristics of low immunogenicity and strong tissue penetration⁴. Studies have shown exosome therapy to reduce wrinkles, enhance neovascularisation, epidermal and collagen tissue regeneration, inhibit hyperpigmentation, reduce inflammation, inhibit scarring and promote hair follicle regeneration and formation.^4,5 As well, exosomes can enhance the effectiveness of other active components, such as hyaluronic acid, peptides and antioxidants.⁶

‘Exosomes can be loaded with cosmetic ingredients to enhance their delivery and efficacy,’ says Dr Turyaki³. ‘For example, they can be engineered to encapsulate ingredients such as peptides, antioxidants and growth factors, which can then be delivered to target cells or tissues for cosmetic benefits. The small size of exosomes allows them to penetrate the deeper layers of the skin, which can increase the bioavailability and effectiveness of the loaded cosmetic ingredients.

‘Exosomes are also biocompatible, which means they are well tolerated by the body and are less likely to cause adverse reactions. This makes them a promising option for cosmetic formulations, as they can be used in various cosmetic products, including creams, serums and masks, without causing significant irritation or other side effects.

‘Furthermore, they can cross biological barriers, such as the blood-brain barrier, which opens up possibilities for their use in products targeting the central nervous system or other hard- to-reach areas of the body. This property can be particularly useful for developing aesthetic products with anti-ageing or skin rejuvenation effects, as they can potentially deliver ingredients to deeper layers of the skin, where they can stimulate collagen production, reduce inflammation and promote skin regeneration.’

Dr Todd Schlesinger, a researcher and board-certified dermatologist from the USA, told IMCAS’ Insider Magazine⁷: ‘Currently exosomes are being used by lots of practitioners for topical use as a cosmetic, and we are seeing huge effects in the skin. We are seeing improvement for scar reduction, improvement for hypertrophic scars as well as keloids, and we are using them a lot in wound healing in post procedure to improve outcomes, enhance results and reduce downtime.

They are also being used as a pre-procedure primary in place of topical antioxidants, growth factors and retinoids.

‘If you have a patient that comes in with a lot of sun damage or with skin that is unhealthy to an extent, you don’t necessarily want to introduce a procedure that is going to be ablative and require a lot of wound healing. This is where we can consider exosomes to help prepare the skin to increase healing capacity.’

Exosomes, senescence & skin rejuvenation

The process of skin ageing is influenced by multiple factors, with one important aspect being the senescence of vital cells, including keratinocytes, fibroblasts and melanocytes.

Exosomes are attracting attention due to their ability to help delay cell ageing8 (such as inhibiting the synthesis of related ageing factor-β-galactosidase (SA-β-Gal)⁹ and inhibiting skin photoageing¹⁰. Another study demonstrates that human- induced potent stem cell-derived exosomes can delay fibroblast senescence¹¹.

Moreover, exosomes derived from various stem cell sources have demonstrated therapeutic implications in tissue regeneration, wound healing and dermatological conditions through mechanisms such as decreased expression of matrix metalloproteinase (MMP), increased collagen and elastin production and modulation of intracellular signaling pathways¹².

In a review of the current literature, published in Plastic & Reconstructive Surgery⁵, the authors note that exosome therapy raises interest by fibroblast proliferation and migration stimulation. ‘In vitro and in vivo studies of UV-B photoaged models have shown that exosome treatment protects cells from UV-B damage by decreasing inflammatory markers, such as tumour necrosis factor alpha (TNF-α), while upregulating TGF-β and tissue inhibitor of MMP (TIMP). These mechanisms led to a reversal of fibroblast senescence with upregulation of collagen I, elastin, and fibronectin production and decreased expression of collagen III,’ the authors write.

Wound healing & scar revision

Exosomes have the potential to positively influence the wound- healing process by affecting various immune and resident tissue cells during the inflammation phase

and initiating extracellular matrix deposition during the proliferation phase. In a 2018 study¹³, exosomes from adipose-derived stem cells (ADSCs) achieved significant results in accelerating wound healing. It was found that ADSCs have the ability to promote cell proliferation and migration – and thereby accelerate wound healing – thanks to the increased levels of type I and III collagen, bFGF, and TGF-B.

Further, exosomes have been shown to promote collagen synthesis and induce neovascularisation in damaged skin¹⁴, enhancing their use in wound healing.

Studies have also shown that exosomes play a role in promoting blood coagulation¹⁵, reducing inflammation¹⁶, accelerating tissue remodelling¹⁷, and inhibiting scar formation¹⁸ by mediating wound repair-related signalling pathways.

A more simplified wound healing process could also improve aesthetic scar outcomes. In the Plastic & Reconstructive Surgery review⁵, the authors note that exosomes derived from various source cell types, including epidermal stem cells, induced pluripotent stem cells and mesenchymal stem cells (adipose tissue, bone marrow and umbilical cord), mitigate collagen production, distribution and the ratio of type III to type I collagen. ‘by increasing the ratio of collagen III to collagen I, adipose-derived exosomes suppress properties associated with poor scarring such as excessive collagen deposition and aberrant cross-linking,’ the authors write.

‘Exosomes are also reported to inhibit myofibroblasts differentiation, keloid fibroblasts / hypertrophic scar fibroblasts proliferation and migration.’

In 2020, Kwon et al¹⁹ published a clinical trial examining exosomes’ potential role in preventing scar formation. Results demonstrated that a combination of adipose- derived exosomes with fractional carbon dioxide laser for facial acne scars yielded less erythema at treatment sites, shorter post- treatment downtime, fewer side effects and overall better outcome compared with fractional carbon dioxide laser treatment alone.

Exosomes in hair restoration

Exosomes offer potential benefits in promoting hair follicle health and stimulating hair growth. They induce hair follicle regeneration by promoting the proliferation of dermal papilla cells and downregulating related hair follicle inhibitory signalling proteins. This process promotes hair follicle stem cell proliferation, hair follicle regeneration and hair follicle formation, transitioning the telogen phase to the growth phase^4,5. Exosomes derived from various source cell types, including dermal papilla, have been found to significantly induce and prolong the anagen phase, resulting in hair growth⁵.

How to use exosomes in the aesthetic clinic

While exosomes can be administered through various methods, including topical application, intravenous therapy, microneedling or direct injection into the treatment area, at the time of writing exosome products in the aesthetics field are advertised for topical use only.

A 2023 review of exosomes in regenerative cosmetic dermatology²⁰ found that the ‘direct application of exosomes following skin rejuvenation procedures – fractional laser, micro-needling, RF microneedling, microdermabrasion – supports the healing process and alleviates associated symptoms such as erythema, oedema and any related discomfort.

‘The anti-inflammatory properties of exosomes allow for faster healing, minimal complications such as post- inflammatory hyperpigmentation and scarring, and allow for better photorejuvenation results due to the enhancement of collagenases and dermal fibroblast proliferation,’ the authors note.

Several clinical trials have explored the efficacy of exosomes in aesthetic treatments. Published in the Journal of Cosmetic Dermatology, Park et al²¹ conducted a 12-week randomised, split-face comparative study involving 28 individuals, demonstrating that the application of human adipose stem cell-derived exosomes in conjunction with microneedling resulted in significantly greater clinical improvements in skin wrinkles, elasticity, hydration and pigmentation than on the non- exosome treated side.

Exosomes have also been assessed as a standalone topical treatment. Proffer et al reported significant improvements in skin health, including reductions in redness and wrinkles from a 6-week clinical trial using a serum containing human platelet- derived exosomes²².

Chernoff et al observed improvements in skin texture, evenness and decreased oiliness using a topical mixture of placental-derived MSC-exosomes combined with other treatments over 30 days²³.

Additionally, Jo et al found that Lactobacillus plantarum-derived exosomes applied to the skin achieved a reduction in eye wrinkles and improvements in skin elasticity, hydration and density in 16 volunteers after 4 weeks of treatment²⁴.

Current challenges

The application of exosomes in aesthetic medicine is still in its early stages, but clinical research is rapidly advancing. Several studies have demonstrated the efficacy of exosome treatments in improving skin quality and accelerating wound healing. However, more extensive clinical trials are needed to fully understand their potential and establish standardised protocols for their use in aesthetic procedures.

Exosomes, despite being plentiful in nature, present challenges in their extraction and preservation due to their small size and susceptibility to environmental factors. In addition, because they can be derived from different tissues in the body, selectively extracting exosomes based on their exact location and their specific contents remains a challenge.

There are currently many methods for isolation and purification of exosomes, but standardised methods are needed to ensure replication of research findings and translating them into practical applications. As the field progresses, overcoming these hurdles will be crucial to unlock the full therapeutic potential of exosomes in clinical practice and personalised medicine.

‘Exosomes are derived from different tissues in the body, such as placental tissue, umbilical stem cells, bone marrow conditioned media, adipose tissue, and mesenchymal tissue to name just a few,’ says Dr Schlesinger3. ‘Different companies are producing exosomes in different ways, and I think that as the science is refined, we’ll find that exosomes will be able to be produced in a more selective way, meaning you will be able to better characterise their size and their contents and fine-tune the contents to contain specific siRNAs, miRNAs, proteins or lipids for clean, targeted delivery.

‘I think that generally physicians can try them in their practice and see how they work for them and their patients. They can enhance the results, and the science that we have so far from different disease states and dermatology and models that we have are positive. As we continue to study their nature and potential uses, we will see more research coming out which will only improve products on the market.’

As research into exosomes continues to progress, their applications in aesthetic medicine are expected to expand. Future developments may include targeted exosome therapies for specific skin conditions, personalised treatments based on individual patient needs, and the combination of exosomes with other modalities – potentially making exosomes an indispensable tool in the aesthetic medical clinic. AMP