Shenzhen Beike Biotechnology Research Institute, Shenzhen 518057, PR China.
Department of Plastic and Aesthetic Surgery, Shenzhen People's Hospital, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen 518055, PR China.
Biomater Adv. 2022 May;136:212781. doi: 10.1016/j.bioadv.2022.212781. Epub 2022 Apr 1.
Application of adipose-derived mesenchymal stromal cells (AMSCs)-derived extracellular vesicles (EVs) in skin wound healing has been documented. In this study, we investigated the therapeutic potential of AMSCs-derived EVs in skin wound healing through delivery of microRNA-10b (miR-10b). HaCaT cells were treated with HO to establish the skin wound cell models. Next, the binding affinity between miR-194, PEA15, and CDK6 was identified. Additionally, EVs were isolated from the culture medium of AMSC sheets, followed by incubation with HO-treated HaCaT cells to detect cell proliferation, migration, and apoptosis using gain- or loss-of-function experiments. Lastly, the mice skin wound models were also established to assess skin wound healing ability. miR-10b was down-regulated in the skin trauma models and enriched in the EVs of AMSC sheets. Moreover, miR-10b derived from EVs targeted PEA15 to promote CDK6 expression, thereby stimulating the proliferation and migration of HO-damaged HaCaT cells but inhibiting apoptosis. In vivo experiments further ascertained the therapeutic functionality of AMSC sheets-derived EVs-miR-10b. In summary, AMSC sheets-derived EVs carrying miR-10b promoted CDK6 expression to intensify skin wound healing by regulating PEA15.
脂肪间充质干细胞(ADSCs)衍生的细胞外囊泡(EVs)在皮肤伤口愈合中的应用已有相关记载。在本研究中,我们通过递送 microRNA-10b(miR-10b),探究了 ADSCs 衍生的 EVs 在皮肤伤口愈合中的治疗潜力。使用 HO 处理 HaCaT 细胞,建立皮肤伤口细胞模型。随后,鉴定 miR-194、PEA15 和 CDK6 之间的结合亲和力。此外,从 ADSC 片的培养上清液中分离 EVs,然后与 HO 处理的 HaCaT 细胞孵育,通过增益或缺失功能实验检测细胞增殖、迁移和凋亡。最后,还建立了小鼠皮肤伤口模型,以评估皮肤伤口愈合能力。miR-10b 在皮肤创伤模型中下调,且在 ADSC 片的 EVs 中富集。此外,来源于 EVs 的 miR-10b 靶向 PEA15 以促进 CDK6 表达,从而刺激 HO 损伤的 HaCaT 细胞的增殖和迁移,但抑制凋亡。体内实验进一步证实了源自 ADSC 片的 EVs-miR-10b 的治疗功能。总之,携带 miR-10b 的 ADSC 衍生的 EVs 通过调节 PEA15 来促进 CDK6 表达,从而增强皮肤伤口愈合。