Exciting Exosomes in Aesthetic Dermatology

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Exosomes are extracellular vesicles produced by all cell types. They are spherical structures 30 to 160 nm in diameter composed of a lipid bilayer encapsulating a variety of biologically active substances including messenger RNA, micro RNA, DNA, proteins, and lipids. They were discovered in 1983 and thought to represent a form of cellular waste disposal. The term “exosome” was coined in 1987 when it was recognized that exosomes represented a form of intercellular communication and a method of macromolecule transmission among cells. Here are answers to the most common questions about exosomes.

How are exosomes created and how do they work?

Exosomes are created by a double invagination process of the originating cell’s plasma membrane, which forms an intracellular multivesicular body that contains intraluminal bodies. The intraluminal bodies release from the originating cell via exocytosis and are then called exosomes. The exosomes are then taken up by a recipient cell and induce a variety of biologic responses, depending on the contents of the exosome, playing a role in cell-to-cell signaling. For example, exosomes containing mRNA can affect protein production in the recipient cell while exosomes containing chemotherapeutic drugs can be used for targeted cancer treatment. Exosomes are released by a variety of cells in the immune system to include B-cells, dendritic cells, and mast cells. Exosomes are also thought to spread disease-associated cargos, such as neurodegenerative-associated peptides found in Alzheimer disease.

Are exosomes present in the skin and what changes do they induce?

Yes, keratinocyte-derived exosomes are manufactured by the body. They appear to modulate melanin synthesis by expressing proteins in melanosomes that control pigmentation. Exosomes can also be derived from dermal fibroblasts where they may induce cell proliferation and alter gene and protein expression in the extracellular matrix.

Where do exosomes come from for aesthetic use?

Exosomes for aesthetic use are derived from adult or mesenchymal stem cells. These cells can be harvested from umbilical cord mesenchymal stem cells or adipose-derived stem cells. The exosomes are isolated by differential centrifugation from culture media. The culture media is first centrifuged to remove higher mass contaminants. The centrifugation then occurs at higher and higher speeds until the exosomes aggregate as a pellet in the bottom of the centrifugation tube. These purified exosomes can then be placed into cosmetic formulations.

What are the dermatologically relevant uses of exosomes?

Exosomes are able to affect angiogenesis, inflammation, apoptosis, and cell proliferation and differentiation. Thus, their uses in dermatology could be far-reaching. Currently investigated potential uses for exosomes in dermatology include scar prevention and treatment, skin rejuvenation, pigmentation regulation, and hair growth. A variety of studies have been conducted, but most are in vitro or in mice. Since exosomes are important in intracellular communication, they could transmit messages to cells that alter behavior and induce anti-aging effects. For example, in cell culture exosomes have been observed to increase procollagen I synthesis and decrease metalloproteinase-1 expression by downregulating TNF-α and TGF-β. This would result in increased dermal collagen production and an aging benefit for mature skin.

Further, cell culture findings demonstrate that keratinocytes communicate with melanocytes via exosomal miRNA, which is microRNA representing a class of noncoding RNAs important in posttranscriptional regulation of gene expression affecting cell growth and differentiation. These keratinocyte exosomes decrease the production of melanin and the expression of tyrosinase in melanocytes, thus improving hyperpigmentation.

Finally, exosomes are being injected subcutaneously for the treatment of androgenetic alopecia. Exosomes can also be obtained from the dermal papillae cells, which are mesenchyme-derived fibroblasts that interact with hair germ cells and stem cells in the hair follicle. These dermal papillae exosomes can stimulate the proliferation and differentiation of the outer root sheath in mice.

What is the future of exosomes in dermatology?

At present, there is no standardized technique for exosome purification or identification of exosome contents. Because exosomes are rapidly degraded when applied topically or subcutaneously injected, frequent application is necessary. Most of the research in exosomes is centered on nanoparticle drug delivery, but the mechanism of action of exosomes has not been completely elucidated. The cargo that exosomes carry may vary and include a mixture of substances not fully identified. Exosomes also play an important role in the immune system involving not only skin disease, but also systemic cancers. There is no doubt that exosomes will be very important in dermatology and represent fertile ground for anti-aging research. There will be much more exciting science to come from exosome technology.

Zoe Diana Draelos, MD, is a consulting professor of dermatology at Duke University School of Medicine in Durham, North Carolina, and Dermatology Times’ Editor in Chief Emeritus.