中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (2): 404-409.doi: 10.4103/1673-5374.346466

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

神经干细胞源性外泌体作为纳米级载体向缺血性脑卒中模型递送脑源性神经营养因子

  

  • 出版日期:2023-02-15 发布日期:2022-08-09
  • 基金资助:

    国家自然科学基金和广东省自然科学基金

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).

摘要:

作者既往的研究证明了人类神经干细胞源性外泌体(hNSC-Exo)对缺血性脑卒中的潜在治疗作用。实验进一步将脑源性神经营养因子(BDNF)转染至神经干细胞源性外泌体中,以构建工程外泌体(BDNF-hNSC-Exo),并比较其与hNSC-Exo的效果。体外实验显示,在H2O2诱导的神经干细胞氧化应激模型中,BDNF-hNSC-Exo明显增强了细胞的生存能力。体内实验显示,BDNF-hNSC-Exo不仅明显抑制了缺血性脑卒中动物模型小胶质细胞的激活,而且还促进了体内内源性神经干细胞向神经元的分化。这些结果表明,BDNF能明显改善神经干细胞衍生的外泌体的功能。我们的研究可能阐明其他神经营养因子对中枢神经系统疾病的临床应用。

https://orcid.org/0000-0002-8075-8369 (Lu-Kui Chen)

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