Exosomes- A New Exciting Antiaging Ingredient!
Exosomes are the new hot antiaging skin care ingredient used for skin rejuvenation. Are exosomes replacing HA serums which are falling out of favor? Suddenly I am seeing companies from several countries touting the benefits of exosomes. But- do they work? Which are best? And what should we be looking for when deciding if an exosome containing product is worth the money?
Exosomes deliver protected and intact RNA and other signaling proteins to target cells.[i] The contents of the exosomes are transferred to the cell, which changes its activity. Exosomes are a safe way to entice cells to have a specific action because they demonstrate very low immunogenicity. [ii]
Why Is Everyone So Excited About Exosomes?
It is now believed that many of the beneficial effects that stem cells have for skin rejuvenation actually come from secreted exosomes.[iii] This means that the same antiaging skin effects can be achieved without having to use actual stem cells which come with a long list of problems outside of the scope of this article. The homing properties of exosomes make them very useful in treating targeted areas.[iv],[v]
What Are Exosomes?
Exosomes are a type of extracellular vesicle[vi] that have a phospholipid bilayer membrane ranging from 30 to 150 nm in diameter. They are found in body tissues and fluids. Cells such as keratinocytes, fibroblasts, and platelets secrete exosomes that have profound effects on the skin and other body tissues.
What are Extracellular Vesicles?
Extracellular vesicles (EVs) are lipid bilayer bound vesicles secreted by cells. EVs can cross from the dermis to epidermis and function as a conduit of communication between cells such as keratinocytes, melanocytes, and fibroblasts.[vii] Exosomes are the smallest and most studied subtype of EV. EVs can carry multiple types of cargo between cells such as proteases (MMPs), inflammatory cytokines, growth factors, mRNA, miRNA, mitochondrial DNA and genomic DNA.
How Do Exosomes Cause Skin Effects?
Exosomes are lipid membrane packets that contain cell signaling molecules that allow cells to communicate with each other. The exosomes are released from the cells and move through body fluids to reach their target to communicate messages.
What Are The Different Types Of Exosomes?
Exosomes vary by origin, size, content, and function. In most of the wound healing studies, mesenchymal stem cell-derived exosomes (MSC-exosomes) have been used. Exosomes derived from platelets have been shown to be effective in ischemic wounds,[viii] rotator cuff tears[ix] and skin rejuvenation.[x] Macrophage derived exosomes accelerate wound healing,[xi] while adipose derived exosomes have reduced scar formation.[xii]
What Do Exosomes Contain?
Exosomes contain different types of contents depending upon their source and function. They may contain mRNA, microRNA, growth factors, and other immune factors. Exosomes can be chosen for use depending on what contents that have. For example, exosomes with large amounts of TGF-β have been to treat ischemic wounds. [xiii]
What Do Exosomes Do?
Inside the exosome sphere is an interluminal space that contains the proteins and nucleic acids and protects them from degradation. [xiv] Exosomes interact with the recipient cells via surface receptor molecules and ligands. When the surface receptors bind the exosome, internalization of the exosome occurs by endocytosis. This allows cells to transfer RNA material and proteins from one cell to another!
Exosomes act on other cells to affect:
Exosomes in skin care
There are significant variations in the source, isolation methods, size and contents of exosomes.[xvii] Therefore it is important to understand that not all exosomes function the same way. This si where we are beginning to see the problem in cosmeceutical claims cropping up. Just because a product has exosomes in it does not mean it has been proven to work. Make sure you know the source of the exosomes and the data behind the product before you get excited about one of these exosome-containing skin care products.
Studies on exosomes:
Exosomes used topically after a microneedling procedure
Exosomes derived from mesenchymal stem cells were placed on skin that had been microneedled and led to an improvement in the skin’s appearance.[xviii] The injury caused by microneedling creates an inflammatory trigger that stimulates the exosomes to respond with regenerating signals. This study clearly showed that when the correct type of exosomes are placed on the skin after microneedling, rejuvenation is seen.
Topical platelet derived exosomes applied twice daily to aged skin
56 participants at the Mayo clinic used a platelet derived exosome product Plated™ Skin Science by Rion) twice daily for 6 weeks. Statistically significant improvement in skin health noted by decreased redness and improvement in wrinkles. It was safe and well tolerated.[xix]
It is certain that the source, quality, and quantity of exosomes has an impact on the outcome.[xx] For this reason we must insist that skin care companies provide details on the types of exosomes they are using in their antiaging products. For now, I am partial to the plated™ Intensive Repair Serum which was was the serum used in the Proffer study.[xxi]
References:
[i] Baumann L Ch 5 Intrinsic Aging in Baumann’s Cosmetic Dermatology Ed. 3 (McGraw Hill 2022)
[ii] Muthu, S., Bapat, A., Jain, R., Jeyaraman, N., & Jeyaraman, M. (2021). Exosomal therapy—A new frontier in regenerative medicine. Stem Cell Investigation, 8.
[iii] Baraniak PR, McDevitt TC. Stem cell paracrine actions and tissue regeneration. Regen Med 2010;5:121e43.
[iv] Prasai, A., Jay, J. W., Jupiter, D., Wolf, S. E., & El Ayadi, A. (2021). Role of Exosomes in Dermal Wound Healing: A Systematic Review. Journal of Investigative Dermatology.
[v] Liu C, Su C. Design strategies and application progress of therapeutic exosomes. Theranostics 2019;9:1015e28.
[vi] L. Baumann Ch. 5 Intrinsic Aging in Baumann’s Cosmetic Dermatology (McGraw Hill 2022)
[vii] Wallis R, Mizen H, Bishop CL. The bright and dark side of extracellular vesicles in the senescence-associated secretory phenotype. Mech Ageing Dev. 2020;189:111263.
[viii] Shi, A., Li, J., Qiu, X., Sabbah, M., Boroumand, S., Huang, T. C. T., … & Moran, S. L. (2021). TGF-β loaded exosome enhances ischemic wound healing in vitro and in vivo. Theranostics, 11(13), 6616.
[ix] Ren, Y., Zhang, S., Wang, Y., Jacobson, D. S., Reisdorf, R. L., Kuroiwa, T., … & Zhao, C. (2021). Effects of purified exosome product on rotator cuff tendon-bone healing in vitro and in vivo. Biomaterials, 276, 121019.
[x] Proffer, S. L., Paradise, C. R., DeGrazia, E., Halaas, Y., Durairaj, K. K., Somenek, M., … & Wyles, S. P. (2022). Efficacy and Tolerability of Topical Platelet Exosomes for Skin Rejuvenation: Six-Week Results. Aesthetic Surgery Journal, 42(10), 1185-1193.
[xi] Li, M., Wang, T., Tian, H., Wei, G., Zhao, L., & Shi, Y. (2019). Macrophage-derived exosomes accelerate wound healing through their anti-inflammation effects in a diabetic rat model. Artificial Cells, Nanomedicine, and Biotechnology, 47(1), 3793-3803.
[xii] Li, C., Wei, S., Xu, Q., Sun, Y., Ning, X., & Wang, Z. (2021). Application of ADSCs and their Exosomes in Scar Prevention. Stem Cell Reviews and Reports, 1-16.
[xiii] Shi, A., Li, J., Qiu, X., Sabbah, M., Boroumand, S., Huang, T. C. T., … & Moran, S. L. (2021). TGF-β loaded exosome enhances ischemic wound healing in vitro and in vivo. Theranostics, 11(13), 6616.
[xiv] Proffer, S. L., Paradise, C. R., DeGrazia, E., Halaas, Y., Durairaj, K. K., Somenek, M., … & Wyles, S. P. (2022). Efficacy and Tolerability of Topical Platelet Exosomes for Skin Rejuvenation: Six-Week Results. Aesthetic Surgery Journal, 42(10), 1185-1193.
[xv] Goodarzi P, Larijani B, Alavi-Moghadam S, Tayanloo-Beik A, MohamadiJahani F, Ranjbaran N, et al. Mesenchymal stem cells-derived exosomes for wound regeneration. Adv Exp Med Biol 2018;1119:119e31.
[xvi] Wang, P., Theocharidis, G., Vlachos, I. S., Kounas, K., Lobao, A., Shu, B., … & Veves, A. (2022). Exosomes derived from epidermal stem cells improve diabetic wound healing. Journal of Investigative Dermatology.
[xvii] Prasai, A., Jay, J. W., Jupiter, D., Wolf, S. E., & El Ayadi, A. (2021). Role of Exosomes in Dermal Wound Healing: A Systematic Review. Journal of Investigative Dermatology.
[xviii] Chernoff, G. (2021). The Utilization of Human Placental Mesenchymal Stem Cell Derived Exosomes in Aging Skin: An Investigational Pilot Study. J Surg, 6, 1388.
[xix] Proffer, S. L., Paradise, C. R., DeGrazia, E., Halaas, Y., Durairaj, K. K., Somenek, M., … & Wyles, S. P. (2022). Efficacy and Tolerability of Topical Platelet Exosomes for Skin Rejuvenation: Six-Week Results. Aesthetic Surgery Journal, 42(10), 1185-1193.
[xx] Zhang, Y., Bi, J., Huang, J., Tang, Y., Du, S., & Li, P. (2020). Exosome: a review of its classification, isolation techniques, storage, diagnostic and targeted therapy applications. International journal of nanomedicine, 15, 6917.
[xxi] Proffer, S. L., Paradise, C. R., DeGrazia, E., Halaas, Y., Durairaj, K. K., Somenek, M., … & Wyles, S. P. (2022). Efficacy and Tolerability of Topical Platelet Exosomes for Skin Rejuvenation: Six-Week Results. Aesthetic Surgery Journal, 42(10), 1185-1193.
