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

Zhi-Han Zhu; Feng Jia; Waqas Ahmed; Gui-Long Zhang; Hong Wang; Chao-Qun Lin; Wang-Hao Chen; Lu-Kui Chen

doi:10.4103/1673-5374.346466

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

Neural Regen Res. 2023 Feb;18(2):404-409. doi: 10.4103/1673-5374.346466.

Authors

Zhi-Han Zhu¹, Feng Jia², Waqas Ahmed¹, Gui-Long Zhang³, Hong Wang¹, Chao-Qun Lin¹, Wang-Hao Chen⁴, Lu-Kui Chen⁵

Affiliations

¹ Department of Neurosurgery, School of Medicine, Southeast University, Nanjing, Jiangsu Province, China.
² Department of Neurosurgery, Neuroscience Center, Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong Province, China.
³ Department of Neurosurgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, China.
⁴ Department of Neurosurgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁵ Department of Neurosurgery, School of Medicine, Southeast University, Nanjing, Jiangsu Province; Department of Neurosurgery, Neuroscience Center, Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong Province, China.

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.

Keywords: brain-derived neurotrophic factor; exosome; inflammation; ischemic stroke; neural stem cell; neurogenesis; neurological recovery; transplantation.