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

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.

• Authors: Wei Huang, Mingjia Qu, Lu Li, Tao Liu, Miaoman Lin, Xiaobing Yu
• Journal: Stem cell research & therapy (Stem Cell Res Ther) Vol. 12 Issue 1 Pg. 334 (06 10 2021) ISSN: 1757-6512 [Electronic] England
• PMID: 34112262 (Publication Type: Journal Article)

Chemical References

• RNA, Small Interfering

Topics

• Animals
• Exosomes (genetics)
• Mesenchymal Stem Cells
• RNA, Small Interfering (genetics)
• Rats
• Rats, Sprague-Dawley
• Spinal Cord
• Spinal Cord Injuries (genetics, therapy)