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

Stem Cell Research & Therapy

Tao Liu¹  Mingjia Qu¹  Lu Li¹  Miaoman Lin¹  Xiaobing Yu¹  Wei Huang² 

[1] Department of Orthopaedics, Affiliated Zhongshan Hospital of Dalian University, No. 6 Jiefang Street, 116001, Dalian, Liaoning Province, China;Department of Orthopaedics, Affiliated Zhongshan Hospital of Dalian University, No. 6 Jiefang Street, 116001, Dalian, Liaoning Province, China;Department of Orthopaedics, Dongguan Tungwah Hospital, No.1 Dongcheng East Road, Dongcheng District, 523000, Dongguan, Guangdong Province, China;

关键词: Spinal cord injury;    Exosomes: Mesenchymal stem cells;    RNA interference;    Small interfering RNA;   

DOI  :  10.1186/s13287-021-02401-x

来源: Springer

【 摘 要 】

BackgroundHow 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.MethodsWe 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,ResultsIn 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).ConclusionsIn 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.

【 授权许可】

CC BY