Neural Regeneration Research ›› 2023, Vol. 18 ›› Issue (10): 2246-2251.doi: 10.4103/1673-5374.369114

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Exosomes from bone marrow mesenchymal stem cells are a potential treatment for ischemic stroke

Chang Liu1, #, Tian-Hui Yang1, #, Hong-Dan Li2, Gong-Zhe Li3, Jia Liang2, *, Peng Wang1, *   

  1. 1Liaoning Provincial Key Laboratory of Neurodegenerative Diseases and Department of Neurobiology, Jinzhou Medical University, Jinzhou, Liaoning Province, China; 2Institute of Life Science, Jinzhou Medical University, Jinzhou, Liaoning Province, China; 3College of Pharmacy, Jinzhou Medical University, Jinzhou, Liaoning Province, China
  • Online:2023-10-15 Published:2023-03-28
  • Contact: Jia Liang, PhD, liangjia@jzmu.edu.cn; Peng Wang, PhD, wangpeng@jzmu.edu.cn.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 81971231 (to JL); the Natural Science Foundation of Liaoning Province, No. 2022-MS-391 (to PW); and the Scientific Research Project from the Education Department of Liaoning Province, Nos. JYTQN2020011 (to PW), LJKQZ2021147 (to JL).

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Abstract: Exosomes derived from human bone marrow mesenchymal stem cells (MSC-Exo) are characterized by easy expansion and storage, low risk of tumor formation, low immunogenicity, and anti-inflammatory effects. The therapeutic effects of MSC-Exo on ischemic stroke have been widely explored. However, the underlying mechanism remains unclear. In this study, we established a mouse model of ischemic brain injury induced by occlusion of the middle cerebral artery using the thread bolt method and injected MSC-Exo into the tail vein. We found that administration of MSC-Exo reduced the volume of cerebral infarction in the ischemic brain injury mouse model, increased the levels of interleukin-33 (IL-33) and suppression of tumorigenicity 2 receptor (ST2) in the penumbra of cerebral infarction, and improved neurological function. In vitro results showed that astrocyte-conditioned medium of cells deprived of both oxygen and glucose, to simulate ischemia conditions, combined with MSC-Exo increased the survival rate of primary cortical neurons. However, after transfection by IL-33 siRNA or ST2 siRNA, the survival rate of primary cortical neurons was markedly decreased. These results indicated that MSC-Exo inhibited neuronal death induced by oxygen and glucose deprivation through the IL-33/ST2 signaling pathway in astrocytes. These findings suggest that MSC-Exo may reduce ischemia-induced brain injury through regulating the IL-33/ST2 signaling pathway. Therefore, MSC-Exo may be a potential therapeutic method for ischemic stroke.

Key words: astrocytes, bone marrow mesenchymal stem cells, brain injury, exosome, IL-33, inflammation, ischemic stroke, neurological function, neuron, ST2