1. Academic Validation
  2. Synergistic effect of mesenchymal stem cell-derived extracellular vesicle and miR-137 alleviates autism-like behaviors by modulating the NF-κB pathway

Synergistic effect of mesenchymal stem cell-derived extracellular vesicle and miR-137 alleviates autism-like behaviors by modulating the NF-κB pathway

  • J Transl Med. 2024 May 13;22(1):446. doi: 10.1186/s12967-024-05257-w.
Qian Qin # 1 Zhiyan Shan # 2 Lei Xing 1 Yutong Jiang 1 Mengyue Li 1 Linlin Fan 1 Xin Zeng 1 Xinrui Ma 1 Danyang Zheng 1 Han Wang 1 Hui Wang 1 Hao Liu 1 Shengjun Liang 1 Lijie Wu 3 Shuang Liang 4
Affiliations

Affiliations

  • 1 Department of Children's and Adolescent Health, Public Health College, Harbin Medical University, Harbin, 150081, China.
  • 2 Department of Histology and Embryology, Harbin Medical University, Harbin, 150081, China.
  • 3 Department of Children's and Adolescent Health, Public Health College, Harbin Medical University, Harbin, 150081, China. wulijiehyd@126.com.
  • 4 Department of Children's and Adolescent Health, Public Health College, Harbin Medical University, Harbin, 150081, China. liangyouyou2004@163.com.
  • # Contributed equally.
Abstract

Autism spectrum disorder (ASD) is a multifaceted neurodevelopmental disorder predominant in childhood. Despite existing treatments, the benefits are still limited. This study explored the effectiveness of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) loaded with miR-137 in enhancing autism-like behaviors and mitigating neuroinflammation. Utilizing BTBR mice as an autism model, the study demonstrated that intranasal administration of MSC-miR137-EVs ameliorates autism-like behaviors and inhibits pro-inflammatory factors via the TLR4/NF-κB pathway. In vitro evaluation of LPS-activated BV2 cells revealed that MSC-miR137-EVs target the TLR4/NF-κB pathway through miR-137 inhibits proinflammatory M1 microglia. Moreover, bioinformatics analysis identified that MSC-EVs are rich in miR-146a-5p, which targets the TRAF6/NF-κB signaling pathway. In summary, the findings suggest that the integration of MSC-EVs with miR-137 may be a promising therapeutic strategy for ASD, which is worthy of clinical adoption.

Keywords

Autism spectrum disorder; Extracellular vesicles; Mesenchymal stem cell; TLR4/NF-κB pathway; miR-137.

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