<p>Topical Application of Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells in Combination with Sponge Spicules for Treatment of Photoaging</p>

Abstract

The topical application of exosomes secreted by mesenchymal stem cells (MSC-Exos) on the skin is a very new and interesting topic in the medical field. In this study, we aimed to investigate whether marine sponge Haliclona sp. spicules (SHSs) could effectively enhance the skin delivery of human umbilical cord-derived MSC-Exos (hucMSC-Exos), and further evaluate the topical application of hucMSC-Exos combined with SHSs in rejuvenating photoaged mouse skin. Materials and Methods: SHSs were isolated from the explants of sponge Haliclona sp. with our proprietary method, and hucMSC-Exos were prepared from the conditioned medium of hucMSCs using ultracentrifugation. The effects of SHSs on the skin penetration of fluorescently labeled hucMSC-Exos were determined using confocal microscopy in vitro (porcine skin) and in vivo (mouse skin). The therapeutic effects of hucMSC-Exos coupled with SHSs against UV-induced photoaging in mice were assessed by using microwrinkles analysis, pathohistological examination and real-time RT-PCR. We also tested the skin irritation caused by the combination of hucMSC-Exos and SHSs in guinea pigs. Results: In vitro results showed that hucMSC-Exos could not readily penetrate through porcine skin by themselves. However, SHSs increased the skin absorption of exosomes by a factor of 5.87 through creating microchannels. Similar penetration enhancement of hucMSC-Exos was observed after SHSs treatment in mice. The combined use of hucMSC-Exos and SHSs showed significant anti-photoaging effects in mice, including reducing microwrinkles, alleviating histopathological changes, and promoting the expression of extracellular matrix constituents, whereas hucMSC-Exos alone produced considerably weaker effects. Skin irritation test showed that the combination of hucMSC-Exos and SHSs caused slight irritation, and the skin recovered shortly. Conclusion: SHSs provide a safe and effective way to enhance the skin delivery of MSC-Exos. Moreover, the combination of MSC-Exos and SHSs may be of much use in the treatment of photoaging.

Exosomal therapy—a new frontier in regenerative medicine

“…Intrathecal is the preferred route in neurodegenerative conditions such as Alzheimer's, Parkinson's, and Creutz-Feld Jakob's disease (98,99). Local aerosol sprays are used in the management of wounds and ulcers (107,108). For hair growth and rejuvenation in age-related therapies, this is the preferred route (108,109).…”

“…Local aerosol sprays are used in the management of wounds and ulcers (107,108). For hair growth and rejuvenation in age-related therapies, this is the preferred route (108,109). During the time of the coronavirus disease-2019 (COVID-19) pandemic, there have been interesting studies discussing the role of exosomal therapy as a promising therapeutic candidate (110).…”

Adipose-Derived Mesenchymal Stem Cells (AD-MSCs) against Ultraviolet (UV) Radiation Effects and the Skin Photoaging

“…The topical application of exosomes secreted by MSCs (MSC-Exos) on the skin is a very new and interesting topic in the medical field. Zhang et al [ 38 ] investigated whether marine sponge Haliclona sp. spicules (SHSs) could effectively enhance the skin delivery of human umbilical cord-derived MSC-Exos (hucMSC-Exos), and further evaluated the topical application of hucMSC-Exos combined with SHSs in rejuvenating photoaged mouse skin.…”

The Role of Exosomes Derived From Mesenchymal Stromal Cells in Dermatology

“…Interestingly, they also found decreased MMP-1 production, which works as a collagenase and encodes a secreted enzyme which breaks down the types I, II, and III interstitial collagens ( Tallant et al, 2010 ; Kim et al, 2017 ). Lastly, Zhang K. et al (2020) studied whether the marine sponge Haliclona sp. spicules (SHSs) could effectively enhance the skin delivery of exosomes from hUC-MSCs by evaluating its topical application in rejuvenating photoaged mouse skin.…”

“…It was reported that the combination of exosomes and SHSs showed significant anti-photoaging effects in mice, including reducing microwrinkles, alleviating histopathological changes and promoting the expression of extracellular matrix constituents. Moreover, skin irritation tests on a guinea pig animal model showed slight irritation ( Zhang K. et al, 2020 ) ( Table 1 and Supplementary Table 3 ).…”