Selenized neural stem cell-derived exosomes: A neotype therapeutic agent for traumatic injuries of the central nervous system
Wenjing Wang, Guihong Lu, Peilin Guo, Haochong Zhang, Yan Wang, Di-Wei Zheng, Chengliang Lyu, Dongfang Wang, Lijun Shang, Feng Li, Jiawei Zhao, Meng Qin, Weiping Li, Hui Tan, Guanghui Ma, Wei Wei
Abstract
Oxidative damage and neuroinflammation are the key features of central nervous system (CNS) injury. Inspired by the neuroprotective properties of neural stem cell-derived exosomes (NExo) and the reactive oxygen species (ROS) scavenging ability of selenium, we develop an advanced NExo bearing ultrasmall nano-selenium (∼3.5 nm) via lipid-mediated nucleation (SeNExo). In addition to maintaining the biological components of NExo, the resulting SeNExo exhibits a Se-O bond that dramatically enhances its ROS-scavenging performance. SeNExo penetrates the blood-brain barrier (BBB) via the apolipoprotein E and prolow-density lipoprotein receptor-related protein 1 (APOE_LRP-1) interaction. Through proteomics, microRNA (miRNA) omics, and single-nucleus RNA sequencing, we find that SeNExo can alleviate neuronal apoptosis, restore glia homeostasis, and remodel glia-neuron networks. Therefore, SeNExo confers potent therapeutic benefits, significantly reducing cerebral lesions in a murine traumatic brain injury model. Even extending to a murine spinal cord injury model, SeNExo promotes locomotory recovery, further supporting SeNExo as a neotype and a promising therapeutic agent for treating traumatic CNS injury.