International Journal of Nanomedicine (Apr 2020)
Topical Application of Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells in Combination with Sponge Spicules for Treatment of Photoaging
Abstract
Keda Zhang,1,2,* Li Yu,3,* Fu-Rong Li,4,* Xue Li,5 Zhefeng Wang,6 Xiaoting Zou,1,2 Chi Zhang,7 Kongpeng Lv,2 Boping Zhou,1 Samir Mitragotri,8 Ming Chen7 1Central Laboratory of Longhua Branch, Second Clinical Medical College (Shenzhen People’s Hospital) of Jinan University, Shenzhen 518109, People’s Republic of China; 2Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou 510632, People’s Republic of China; 3Department of Plastic and Aesthetic Surgery, Second Clinical Medical College (Shenzhen People’s Hospital) of Jinan University, Shenzhen 518020, People’s Republic of China; 4Translational Medicine Collaborative Innovation Center, Second Clinical Medical College (Shenzhen People’s Hospital) of Jinan University, Shenzhen, 518020, People’s Republic of China; 5Institute of Mass Spectrometry and Atmospheric Environment, Jinan University, Guangzhou 510632, People’s Republic of China; 6Department of Cardiology, Second Clinical Medical College (Shenzhen People’s Hospital) of Jinan University, Shenzhen 518020, People’s Republic of China; 7State-Province Joint Engineering Laboratory of Marine Bioproducts and Technology, College of Ocean and Earth Sciences, Xiamen University, Xiamen 361102, People’s Republic of China; 8School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA*These authors contributed equally to this workCorrespondence: Ming Chen; Boping Zhou Email [email protected]; [email protected]: 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.Keywords: exosomes, mesenchymal stem cell, skin delivery, marine sponge spicules, photoaging
