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; Diwei Zheng; Chengliang Lyu; Dongfang Wang; Shang Li; Feng Li; Jiawei Zhao; Meng Qin; Weiping Li; Hui Tan; Guanghui Ma; Wei Wei

doi:10.1016/j.xcrm.2025.102319

Selenized neural stem cell-derived exosomes: A neotype therapeutic agent for traumatic injuries of the central nervous system

Cell Rep Med. 2025 Sep 16;6(9):102319. doi: 10.1016/j.xcrm.2025.102319. Epub 2025 Aug 28.

Authors

Wenjing Wang¹, Guihong Lu², Peilin Guo³, Haochong Zhang⁴, Yan Wang⁵, Diwei Zheng⁵, Chengliang Lyu⁵, Dongfang Wang⁶, Shang Li⁴, Feng Li⁵, Jiawei Zhao⁵, Meng Qin⁷, Weiping Li⁸, Hui Tan⁹, Guanghui Ma¹⁰, Wei Wei¹¹

Affiliations

¹ State Key Laboratory of Biopharmaceutical Preparation and Delivery, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, P.R. China; Department of Neurosurgery, Shenzhen Key Laboratory of Neurosurgery, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen 518035, P.R. China.
² Center for Child Care and Mental Health (CCCMH), Shenzhen Children's Hospital, Shenzhen 518026, P.R. China.
³ State Key Laboratory of Biopharmaceutical Preparation and Delivery, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, P.R. China; School of Chemical Engineering, University of Chinese Academy of Sciences, Beijing 100049, P.R. China.
⁴ Senior Department of Orthopedics, the Fourth Medical Center of Chinese PLA General Hospital, Beijing 100089, P.R. China.
⁵ State Key Laboratory of Biopharmaceutical Preparation and Delivery, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, P.R. China.
⁶ Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing 100871, P.R. China.
⁷ Mental Health Center and Center for Preclinical Safety Evaluation of Drugs, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
⁸ Department of Neurosurgery, Shenzhen Key Laboratory of Neurosurgery, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen 518035, P.R. China. Electronic address: wpli@szu.edu.cn.
⁹ Center for Child Care and Mental Health (CCCMH), Shenzhen Children's Hospital, Shenzhen 518026, P.R. China; Department of Neurosurgery, Shenzhen Key Laboratory of Neurosurgery, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen 518035, P.R. China. Electronic address: huitan@email.szu.edu.cn.
¹⁰ State Key Laboratory of Biopharmaceutical Preparation and Delivery, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, P.R. China; School of Chemical Engineering, University of Chinese Academy of Sciences, Beijing 100049, P.R. China. Electronic address: ghma@ipe.ac.cn.
¹¹ State Key Laboratory of Biopharmaceutical Preparation and Delivery, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, P.R. China; School of Chemical Engineering, University of Chinese Academy of Sciences, Beijing 100049, P.R. China. Electronic address: weiwei@ipe.ac.cn.

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.

Keywords: exosomes; neuroinflammation; oxidative stress; selenium; traumatic brain injury; traumatic spinal cord injury.

MeSH terms

Animals
Apolipoproteins E / metabolism
Apoptosis / drug effects
Blood-Brain Barrier / metabolism
Brain Injuries, Traumatic* / pathology
Brain Injuries, Traumatic* / therapy
Central Nervous System* / pathology
Disease Models, Animal
Exosomes* / metabolism
Humans
Male
Mice
Mice, Inbred C57BL
MicroRNAs / genetics
MicroRNAs / metabolism
Neural Stem Cells* / cytology
Neural Stem Cells* / metabolism
Neurons / metabolism
Neuroprotective Agents / pharmacology
Reactive Oxygen Species / metabolism
Spinal Cord Injuries / pathology
Spinal Cord Injuries / therapy

Substances

MicroRNAs
Reactive Oxygen Species
Neuroprotective Agents
Apolipoproteins E