EXOSOMES

Consultant plastic surgeon and founder of the London Regenerative Institute Mr Tunc Tiryaki reveals the results of the latest clinical study on the rejuvenating effects of exosomes .

WHAT ARE EXOSOMES?

Exosomes are tiny structures that are found inside cells. They are like small bubbles or vesicles that are released by cells and can travel to other cells in the body. Think of them as “cellular messengers” that transmit important information between cells.1,2

Exosomes are made up of a lipid bilayer, which is a double layer of fats that surrounds and protects their contents. Inside the exosome, there can be various types of molecules, such as proteins, lipids, and nucleic acids, like DNA and RNA.3,4

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. 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.3-6

THE BEAUTY OF EXOSOMES

Exosomes have gained attention in the cosmetic industry due to their unique properties, including their small size, biocompatibility, and ability to cross biological barriers, such as the blood-brain barrier.7In the aesthetic industry, exosomes can be loaded with cosmetic ingredients to enhance their delivery and efficacy. For example, they can be engineered to encapsulate cosmetic ingredients such as peptides, antioxidants, and growth factors, which can then be delivered to target cells or tissues for cosmetic benefits. 2,8,9The 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. 10Exosomes are also biocompatible, which means they are well tolerated by the body and are less likely to cause adverse reactions. 2This 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. 11-12Furthermore, 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.

1- 2 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. 10,13,14

REGENERATIVE PROPERTIES

The use of cord blood exosomes, specifically derived from umbilical cord blood, has gained attention in recent years due to their potential regenerative properties. The combination of constructive miRNAs and growth factors in them works synergistically to promote regenerative processes in target cells and tissues. By delivering specific miRNAs and growth factors, cord blood exosomes can provide regenerative signals that promote tissue repair, modulate inflammation, and support cell survival and growth, making them a promising therapeutic option for regenerative medicine.15-19

The cream formulation containing ‘hybrosomes’, the cord blood exosome ingredient, was developed to harness the potential regenerative properties of exosomes for skincare or other cosmetic purposes.

CLINICAL STUDY TO COMPARE THE EFFECTS OF FOUR DIFFERENT CREAM FORMULATIONS ON WRINKLES AND ELASTICITY

THE FOUR CREAM FORMULATIONS USED IN THE STUDY WERE:

A study was designed so that participants were randomly assigned to different groups, such as a treatment group using the cream formulation with hybrosome base cream, a control group using a placebo or another product without hybrosome and a negative control group as 0.2% retinol combined with base cream. This random assignment helped to ensure that any observed effects for wrinkle reduction, transepidermal water loss, melanin level and regeneration capacity related to skin-ageing were also evaluated.

Participants were randomly assigned to one of the four cream formulations. The study design was single-blinded, meaning that the participants did not know which cream formulation they were using, but the researchers knew the details of each cream formulation. This helps to minimise bias in the results. The effects of the different cream formulations on wrinkles and skin elasticity were assessed at specific time points, such as before the study, and at regular intervals during the study period. Various methods, such as skin measurements, questionnaires assessed the changes in wrinkles and elasticity.

METHOD

Ten female volunteers aged between 40-56 years having no skin or other diseases were selected for the study and consent was taken. The volunteers were not informed about the contents of the creams. All volunteers selected for the study met the requirements for inclusion, signed consent to voluntary participation and were informed about the purpose of the study, how it was conducted and possible side effects. During the entire study, the volunteers were under the constant care of a dermatologist.

Each volunteer for the study, which was conducted at home, was provided with a cream, and applied it once a day for four weeks. The test was performed in accordance with the research procedure of Skin Lab International Sp. z o.o. (PO-08 Research implementation) under the supervision of a specialist. Volunteers qualified for the study received the tested product and a prepared questionnaire. They were informed about the conditions of the study as well as the area and frequency of product application. Skin parameters were measured at the Skin Lab International Laboratory in Krakow following a previously agreed plan. Measurements are carried out using Derma Lab Combo and ASW 300 measuring devices.

Wrinkle analysis would involve assessing the presence and severity of wrinkles on the skin, which could be subjective or objective measures. Elasticity measurement in cosmetics typically refers to the assessment of the skin’s ability to stretch and rebound. Skin elasticity is an important parameter in the cosmetic industry, as it is associated with youthful, healthy-looking skin.

FINDINGS

It appears that there is a minimal difference in the percentage of wrinkle removal between the base cream alone (11.4%) and the base cream combined with retinol formulation (11.5%). This difference is not statistically significant.

All hybrosome creams have been found to be approximately 30% more effective in reducing wrinkles and 22% more effective in elasticity when compared to base cream or base cream retinol used alone.

Figure 1: (A) Comparison of different cream formulations in anti-wrinkle and elasticity (B) Visual of different cream formulations in anti-wrinkle and elasticity (C) The effect of hybrosome cream on forehead wrinkles and crow’s feet wrinkles at the end of Day 0 and Day 56.

CONCLUSIONS

As a result of clinical studies, it has been seen that cream formulation with hybrosome molecules reduces the wrinkle area, increases the elasticity, as well as gives better results in wrinkle area and TEWL recovery against the gold standard retinol. The recovery of the forehead and crow’s feet wrinkle areas, as well as the melanin level results of hybrosome molecules, improved in direct proportion to the usage.

Exosomes have gained significant attention in recent years due to their potential clinical applications in various fields, including as intravenous (IV) therapies, micro-needling, and in cosmetic products. They hold great promise for various clinical applications, further research and clinical trials are needed to establish their safety, efficacy, and optimal use in IV therapies. Exosome treatments show promising potential for topical and cosmetic use in various clinical applications.10,11Moreover, exosome-based skincare treatments are also being explored for other clinical applications, such as wound healing, hair regrowth, and scar reduction. For this reason, it can be predicted that exosome treatments will have great importance in our clinics in 12, 19 a very short time.

Hybrosome biotech skincare brand Morphiya is one of the first topical exosome products to launch and Morphiya’s “Genesis Formula’’ is available now. For further information about Morphiya and how it can be used in-clinic and on patients, contact info@recure.co.uk

REFERENCES

1. Bu H, He D, He X, Wang K. Exosomes: Isolation, Analysis, and Applications in Cancer Detection and Therapy. Chembiochem. 2019 Feb 15;20(4):451-461. doi: 10.1002/cbic.201800470. Epub 2018 Dec 7. PMID: 30371016.

2. Kul, Y. and Erbaş, O., 2022. Exosomes: Classification, Isolation, and Therapeutic Applications in Various Diseases. Journal of Experimental and Basic Medical Sciences, 3(1), pp.006-012.

3. Ju Y, Bai H, Ren L, Zhang L. The Role of Exosome and the ESCRT Pathway on Enveloped Virus Infection. Int J Mol Sci. 2021 Aug 22;22(16):9060. doi: 10.3390/ijms22169060. PMID: 34445766; PMCID: PMC8396519.

4. Chen H, Wang L, Zeng X, Schwarz H, Nanda HS, Peng X, Zhou Y. Exosomes, a New Star for Targeted Delivery. Front Cell Dev Biol. 2021 Oct 8;9:751079. doi: 10.3389/fcell.2021.751079. PMID: 34692704; PMCID: PMC8531489.

5. Liu Q, Li S, Dupuy A, Mai HL, Sailliet N, Logé C, Robert JH, Brouard S. Exosomes as New Biomarkers and Drug Delivery Tools for the Prevention and Treatment of Various Diseases: Current Perspectives. Int J Mol Sci. 2021 Jul 21;22(15):7763. doi: 10.3390/ijms22157763. PMID: 34360530; PMCID: PMC8346134.

6. Vizoso FJ, Eiro N, Cid S, SchneiderJ, Perez-Fernandez R. Mesenchymal Stem Cell Secretome: Toward Cell-Free Therapeutic Strategies in Regenerative Medicine. Int J Mol Sci. 2017 Aug 25;18(9):1852. doi: 10.3390/ijms18091852. PMID: 28841158; PMCID: PMC5618501.

7. Szwedowicz U, Łapińska Z, Gajewska-Naryniecka A, Choromańska A. Exosomes and Other Extracellular Vesicles with High Therapeutic Potential: TheirApplications in Oncology, Neurology, and Dermatology. Molecules. 2022 Feb 15;27(4):1303. doi: 10.3390/ molecules27041303. PMID: 35209095; PMCID: PMC8879284.

8. Bian D, Wu Y, Song G, Azizi R, Zamani A. The application of mesenchymal stromal cells (MSCs) and their derivative exosome in skin wound healing: a comprehensive review. Stem Cell Res Ther. 2022 Jan 24;13(1):24. doi: 10.1186/s13287-021-02697-9. PMID: 35073970; PMCID: PMC8785459.

9. Tenchov R, Sasso JM, Wang X, Liaw WS, Chen CA, Zhou QA. Exosomes Nature’s Lipid Nanoparticles, a Rising Star in Drug Delivery and Diagnostics. ACS Nano. 2022 Nov 22;16(11):17802-17846. doi: 10.1021/acsnano.2c08774. Epub 2022 Nov 10. PMID: 36354238; PMCID: PMC9706680.

10. Kee LT, Ng CY, Al-Masawa ME, Foo JB, How CW, Ng MH, LawJX. Extracellular Vesicles in Facial Aesthetics: A Review. Int J Mol Sci. 2022 Jun 16;23(12):6742. doi: 10.3390/ijms23126742. PMID: 35743181; PMCID: PMC9223821.

11. Salvioni L, Morelli L, Ochoa E, Labra M, Fiandra L, Palugan L, Prosperi D, Colombo M. The emerging role of nanotechnology in skincare. Adv Colloid Interface Sci. 2021 Jul;293:102437. doi: 10.1016/j.cis.2021.102437. Epub 2021 May 11. PMID: 34023566.

12. Wu JY, Wu SN, Zhang LP, Zhao XS, Li Y, Yang QY, Yuan RY, Liu JL, Mao HJ, Zhu NW. Stem Cell-Derived Exosomes: A New Method for Reversing Skin Aging. Tissue Eng Regen Med. 2022 Oct;19(5):961-968. doi: 10.1007/s13770-022-00461-5. Epub 2022 Jul 9. PMID: 35809187; PMCID: PMC9477989.

13. Lv J, Yang S, Lv M, Lv J, Sui Y, Guo S. Protective roles of mesenchymal stem cells on skin photoaging: Anarrative review. Tissue Cell. 2022 Jun;76:101746. doi: 10.1016/j.tice.2022.101746. Epub 2022 Jan 29. PMID: 35182986.

14. Csekes E, Račková L. Skin Aging, Cellular Senescence and Natural Polyphenols. Int J Mol Sci. 2021 Nov 23;22(23):12641. doi: 10.3390/ijms222312641. PMID: 34884444; PMCID: PMC8657738.

15. Roura S, Vives J. Extracellular vesicles: Squeezing every drop of regenerative potential of umbilical cord blood. Metabolism. 2019 Jun;95:102-104. doi: 10.1016/j.metabol.2019.02.006. Epub 2019 Mar 1. PMID: 30831143.

16. Hu Y, Rao SS, Wang ZX, Cao J, Tan YJ, Luo J, Li HM, Zhang WS, Chen CY, Xie H. Exosomes from human umbilical cord blood accelerate cutaneous wound healing through miR-21- 3p-mediated promotion of angiogenesis and fibroblast function. Theranostics. 2018 Jan 1;8(1):169-184. doi: 10.7150/thno.21234. PMID: 29290800; PMCID: PMC5743467.

17. Zhang Y, Pan Y, Liu Y, Li X, Tang L, Duan M, Li J, Zhang G. Exosomes derived from human umbilical cord blood mesenchymal stem cells stimulate regenerative wound healing via transforming growth factor-receptor inhibition. Stem Cell Res Ther. 2021 Aug 3;12(1):434. doi: 10.1186/s13287-021-02517-0. PMID: 34344478; PMCID: PMC8336384.

18. Cleys ER, Halleran JL, McWhorter E, HergenrederJ, Enriquez VA, da Silveira JC, Bruemmer JE, Winger QA, Bouma GJ. Identification of microRNAs in exosomes isolated from serum and umbilical cord blood, as well as placentomes of gestational day 90 pregnant sheep. Mol Reprod Dev. 2014 Nov;81(11):983-93. doi: 10.1002/mrd.22420. Epub 2014 Sep 30. PMID: 25269776.

 19. Hu Y, Rao SS, Wang ZX, Cao J, Tan YJ, Luo J, Li HM, Zhang WS, Chen CY, Xie H. Exosomes from human umbilical cord blood accelerate cutaneous wound healing through miR-21- 3p-mediated promotion of angiogenesis and fibroblast function. Theranostics. 2018 Jan 1;8(1):169-184. doi: 10.7150/thno.21234. PMID: 29290800; PMCID: PMC5743467.