Exosomes Secreted by Hypoxia-Pre-conditioned Adipose-Derived Mesenchymal Stem Cells Reduce Neuronal Apoptosis in Rats with Spinal Cord Injury

被引:50
作者
Liang, Yan [1 ,2 ]
Wu, Jian-Huang [1 ,2 ]
Zhu, Jing-Hui [1 ,2 ]
Yang, Hui [3 ]
机构
[1] Cent South Univ, Dept Spine Surg & Orthped, Hunan, Peoples R China
[2] Cent South Univ, Natl Clin Res Ctr Geriatr Disorders, Hunan, Peoples R China
[3] Cent South Univ, Xiangya Hosp, Dept Radiol, Changsha, Peoples R China
基金
中国国家自然科学基金;
关键词
apoptosis; exosomes; hypoxic condition; miRNA; oxygen-glucose deprivation and reperfusion; spinal cord injury; EXTRACELLULAR VESICLES; ANGIOGENESIS; AP-1; PROLIFERATION; MIGRATION;
D O I
10.1089/neu.2021.0290
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Neuronal death is the main cause of nerve function impairment after spinal cord injury (SCI). Exosome-based therapy has become a novel strategy for tissue injury repair. We designed a method to treat SCI using exosomes secreted by adipose tissue-derived stromal cells (ADSCs) under hypoxic conditions. We established a neuronal oxygen-glucose deprivation and reperfusion (OGD/R) model in vitro to simulate the hypoxic environment after SCI. We observed that exosomes derived from hypoxia-conditioned ADSCs (Hypo-exo) significantly reduced neuronal apoptosis after OGD. By establishing a rat SCI model, we found that Hypo-exo can significantly reduce the formation of cavities in the injured area and improve the functional recovery of the hindlimbs of rats after injury. To explore the molecular mechanism, we conducted microRNA sequencing analysis of exosomes. Through real-time polymerase chain reaction, dual luciferase reporter assays and signaling pathway chip analysis, we determined that miR-499a-5p regulates the JNK3/c-jun-apoptotic signaling pathway by targeting JNK3. Further, we verified the expression of the key proteins in the JNK3/c-jun-apoptotic signaling pathway by immunofluorescence and Western blotting. These results support the hypothesis that Hypo-exo can reduce neuronal apoptosis after SCI and may provide new methods to treat SCI.
引用
收藏
页码:701 / 714
页数:14
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