Neural Regeneration Research ›› 2023, Vol. 18 ›› Issue (2): 404-409.doi: 10.4103/1673-5374.346466

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Neural stem cell-derived exosome as a nano-sized carrier for BDNF delivery to a rat model of ischemic stroke

Zhi-Han Zhu1, Feng Jia2, Waqas Ahmed1, Gui-Long Zhang3, Hong Wang1, Chao-Qun Lin1, Wang-Hao Chen4, Lu-Kui Chen1, 2, *   

  1. 1Department of Neurosurgery, School of Medicine, Southeast University, Nanjing, Jiangsu Province, China; 2Department of Neurosurgery, Neuroscience Center, Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong Province, China; 3Department of Neurosurgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, China; 4Department of Neurosurgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  • Online:2023-02-15 Published:2022-08-09
  • Contact: Lu-Kui Chen, MD, neuro_clk@hotmail.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 81671819 (to LKC), and the Natural Science Foundation of Guangdong Province, Nos. 2021A1515010001 and 2019A1515012103 (both to LKC).

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Abstract: Our previous study demonstrated the potential therapeutic role of human neural stem cell-derived exosomes (hNSC-Exo) in ischemic stroke. Here, we loaded brain-derived neurotrophic factor (BDNF) into exosomes derived from NSCs to construct engineered exosomes (BDNF-hNSC-Exo) and compared their effects with those of hNSC-Exo on ischemic stroke both in vitro and in vivo. In a model of H2O2-induced oxidative stress in NSCs, BDNF-hNSC-Exo markedly enhanced cell survival. In a rat middle cerebral artery occlusion model, BDNF-hNSC-Exo not only inhibited the activation of microglia, but also promoted the differentiation of endogenous NSCs into neurons. These results suggest that BDNF can improve the function of NSC-derived exosomes in the treatment of ischemic stroke. Our research may support the clinical use of other neurotrophic factors for central nervous system diseases.

Key words: brain-derived neurotrophic factor, exosome, inflammation, ischemic stroke, neural stem cell, neurogenesis, neurological recovery, transplantation