Central Laboratory of Longhua Branch, Second Clinical Medical College (Shenzhen People's Hospital) of Jinan University, Shenzhen 518109, People's Republic of China.
Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou 510632, People's Republic of China.
Int J Nanomedicine. 2020 Apr 23;15:2859-2872. doi: 10.2147/IJN.S249751. eCollection 2020.
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 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.
SHSs were isolated from the explants of sponge 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.
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.
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.
间充质干细胞（MSC-Exos）分泌的细胞外囊泡（Exos）的局部应用是医学领域一个非常新且有趣的课题。本研究旨在探讨海洋海绵 sp. 骨针（SHSs）是否能有效促进人脐带间充质干细胞来源的 MSC-Exos（hucMSC-Exos）在皮肤中的传递，并进一步评估 hucMSC-Exos 与 SHSs 联合应用于光老化小鼠皮肤再生的效果。
采用专利方法从海绵 sp. 的外植体中分离出 SHSs，采用超速离心法从 hucMSCs 的条件培养基中制备 hucMSC-Exos。采用共聚焦显微镜分别在体外（猪皮）和体内（鼠皮）研究 SHSs 对荧光标记 hucMSC-Exos 皮肤渗透的影响。采用微皱纹分析、组织病理学检查和实时 RT-PCR 评估 hucMSC-Exos 与 SHSs 联合治疗对紫外线诱导的光老化小鼠的疗效。我们还在豚鼠中测试了 hucMSC-Exos 与 SHSs 联合使用引起的皮肤刺激。
体外结果显示，hucMSC-Exos 本身不易穿透猪皮。然而，SHSs 通过制造微通道将外泌体的皮肤吸收率提高了 5.87 倍。SHSs 处理后，在小鼠中也观察到 hucMSC-Exos 有类似的渗透增强效果。hucMSC-Exos 与 SHSs 联合使用在小鼠中表现出显著的抗光老化作用，包括减少微皱纹、缓解组织病理学改变和促进细胞外基质成分的表达，而 hucMSC-Exos 单独使用则产生的效果较弱。皮肤刺激试验表明，hucMSC-Exos 与 SHSs 的联合使用会引起轻微刺激，但皮肤很快恢复。
SHSs 为 MSC-Exos 的皮肤传递提供了一种安全有效的方法。此外，MSC-Exos 与 SHSs 的联合使用可能在光老化治疗中具有很大的应用价值。
