Umbilical cord mesenchymal stem cell‐derived exosomes promote axon regeneration during optic nerve injury through microRNA‐dependent mTORC1 signalling

作者：Xuan Sang, Lei Tang, Liang Zhao, Nana Xu, Feng Liu, Yuhui Shen, Wei Wei, Yaqi Cheng, Wanjing Huang, Yurun Liu, Yaru Su, Chao Xu, Yongsheng Li, Zhichong Wang, Sheng Liu · 发表于：Clinical and Translational Medicine · 年份：2023 · DOI：10.1002/ctm2.1319 · 被引用次数：20 · 研究领域：Extracellular vesicles in disease、RNA Interference and Gene Delivery、MicroRNA in disease regulation

Dear Editor, Treatment for optic nerve (ON) injury remains a challenge worldwide. As essential paracrine signals of mesenchymal stem cells (MSCs), exosomes (exos) show source cell-like biological functions, which have recently been suggested to promote the functional recovery of central neurons.1-4 Reportedly, MSC-exos transfer active components, especially microRNAs (miRNAs), to facilitate intercellular communication, thereby exerting tissue regenerative effects.5-8 However, the effect of exos derived from umbilical cord MSCs (HuMSC-exos) and the underlying mechanisms in ON injury remain unclear. Here, we intended to explore whether HuMSC-exos have a neuroregenerative effect and the molecular mechanisms by which exosomal miRNAs play a role in this process. Exos were isolated from HuMSCs (Figure S1A–C) and purified by ultracentrifugation. Purified HuMSC-exos were identified by positive expression of their specific surface markers (CD9, CD63 and TSG101) by Western blotting (Figure S2A–E). They displayed typical exosomal features, including morphology and size, as detected by transmission electron microscopy (Figure S2F). Nanoparticle tracking analysis revealed that purified HuMSC-exos were relatively homogeneous particles, and the particle concentration in the distribution range of 30–200 nm was approximately 93.3% (Figure S2G). In the ON crush (ONC) model, HuMSC-exos promoted the survival of 30% of the retinal ganglion cells (RGCs) (Figure 1A,B), rescued 60% of the RGCs from ...