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外泌体来源的 MSC-siRNA 沉默 CTGF 基因促进大鼠脊髓损伤运动功能恢复。

SiRNA in MSC-derived exosomes silences CTGF gene for locomotor recovery in spinal cord injury rats.

机构信息

Department of Orthopaedics, Affiliated Zhongshan Hospital of Dalian University, No. 6 Jiefang Street, Dalian, 116001, Liaoning Province, China.

Department of Orthopaedics, Dongguan Tungwah Hospital, No.1 Dongcheng East Road, Dongcheng District, Dongguan, 523000, Guangdong Province, China.

出版信息

Stem Cell Res Ther. 2021 Jun 10;12(1):334. doi: 10.1186/s13287-021-02401-x.

DOI:10.1186/s13287-021-02401-x
PMID:34112262
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8193895/
Abstract

BACKGROUND

How to obtain a small interfering RNA (siRNA) vector has become a moot point in recent years. Exosomes (Exo) show advantages of long survival time in vivo, high transmission efficiency, and easy penetration across the blood-spinal cord barrier, renowned as excellent carriers of bioactive substances.

METHODS

We applied mesenchymal stem cell (MSC)-derived exosomes as the delivery of synthesized siRNA, which were extracted from rat bone marrow. We constructed exosomes-siRNA (Exo-siRNA) that could specifically silence CTGF gene in the injury sites by electroporation. During the administration, we injected Exo-siRNA into the tail vein of SCI rats, RESULTS: In vivo and in vitro experiments showed that Exo-siRNA not only effectively inhibited the expressions of CTGF gene, but quenched inflammation, and thwarted neuronal apoptosis and reactive astrocytes and glial scar formation. Besides, it significantly upregulated several neurotrophic factors and anti-inflammatory factors, acting as a facilitator of locomotor recovery of rats with spinal cord injury (SCI).

CONCLUSIONS

In conclusion, this study has combined the thoroughness of gene therapy and the excellent drug-loading characteristics of Exo for the precise treatment of SCI, which will shed new light on the drug-loading field of Exo.

摘要

背景

近年来，如何获得小干扰 RNA（siRNA）载体已成为一个悬而未决的问题。外泌体（Exo）具有体内存活时间长、传递效率高、易穿透血脊屏障等优点，被誉为生物活性物质的优良载体。

方法

我们应用骨髓间充质干细胞（MSC）衍生的外泌体作为合成 siRNA 的递药载体，这些外泌体是通过电穿孔从大鼠骨髓中提取的。我们构建了能够特异性沉默损伤部位 CTGF 基因的外泌体-siRNA（Exo-siRNA）。在给药过程中，我们将 Exo-siRNA 经尾静脉注入 SCI 大鼠体内。

结果

体内和体外实验表明，Exo-siRNA 不仅能有效抑制 CTGF 基因的表达，还能抑制炎症反应，阻止神经元凋亡和反应性星形胶质细胞及胶质瘢痕形成，同时显著上调几种神经营养因子和抗炎因子，促进脊髓损伤（SCI）大鼠运动功能恢复。

结论

综上所述，本研究将基因治疗的彻底性与外泌体的优良载药特性相结合，为 SCI 的精准治疗提供了新的思路，也为外泌体的载药领域带来了新的曙光。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b5a/8193895/9cb3bebc291a/13287_2021_2401_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b5a/8193895/8e6ea864202e/13287_2021_2401_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b5a/8193895/bc63fcf15694/13287_2021_2401_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b5a/8193895/dfb0f771bd5a/13287_2021_2401_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b5a/8193895/9ef5c2546985/13287_2021_2401_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b5a/8193895/9cb3bebc291a/13287_2021_2401_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b5a/8193895/8e6ea864202e/13287_2021_2401_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b5a/8193895/bc63fcf15694/13287_2021_2401_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b5a/8193895/dfb0f771bd5a/13287_2021_2401_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b5a/8193895/9ef5c2546985/13287_2021_2401_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b5a/8193895/9cb3bebc291a/13287_2021_2401_Fig5_HTML.jpg

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