Abstract
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.
Highlights
How to obtain a small interfering RNA vector has become a moot point in recent years
The results of flow cytometry showed that mesenchymal stem cells (MSCs) highly expressed CD29 (94.5%) and CD90 (92.5%) and lowly expressed CD45 (0.15%), which were consistent with the characteristics of rat bone marrow MSCs (Fig. 1b)
The results showed that the expression of calnexin of MSCs was significantly higher than that MSC-Exo, which proved that calnexin was a unique marker of cells (Fig. 1d)
Summary
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. Recent studies have explained that the exosomes (Exo) secreted from mesenchymal stem cells (MSCs) may take the central role behind their potential therapeutic effect on SCI [3, 4]. Apart from Exo’s penetration across the blood-brain/spinal cord barrier depending on their small size, they manifest a Exosomes is nano-sized vesicles with the diameter of 30–200 nm secreted by various cells [7]. In the experiment of central nervous system injury, MSC-Exo have facilitated the growth of axons of cortical neurons. MSCExo have been systemically administered to promote
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