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

• Published in: Stem cell research & therapy Vol. 12; no. 1; pp. 1 - 334
• Main Authors: Huang, Wei, Qu, Mingjia, Li, Lu, Liu, Tao, Lin, Miaoman, Yu, Xiaobing
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 10.06.2021; BioMed Central; BMC
• Subjects: Apoptosis; Astrocytes; Bone marrow; Connective tissue growth factor; Efficiency; Electroporation; Exosomes; Exosomes: Mesenchymal stem cells; Gene therapy; Genes; Genetic engineering; Hypoxia; Inflammation; Mesenchymal stem cells; Mesenchyme; Nervous system; Neuronal-glial interactions; Neurotrophic factors; RNA; RNA interference; siRNA; Small interfering RNA; Spinal cord injuries; Spinal cord injury; Stem cells; China; United States > US
• ISSN: 1757-6512; 1757-6512
• DOI: 10.1186/s13287-021-02401-x

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. Keywords: Spinal cord injury, Exosomes: Mesenchymal stem cells, RNA interference, Small interfering RNA