Exosomes (Exo) exhibit numerous advantages (e.g., good encapsulation, high targeting efficiency, and easy to penetrate the blood-brain barrier to the central nervous system). Exosomes are recognized as prominent carriers of mRNAs, siRNAs, miRNAs, proteins, and other bioactive molecules. As confirmed by existing studies, miR-494 is important to regulate the occurrence, progression, and repair of spinal cord injury (SCI). We constructed miR-494-modified exosomes (Exo-miR-494). As indicated from related research in vitro and vivo, Exo-miR-494 is capable of effectively inhibiting the inflammatory response and neuronal apoptosis in the injured area, as well as upregulating various anti-inflammatory factors and miR-494 to protect neurons. Moreover, it can promote the regeneration of the neurofilament and improve the recovery of behavioral function of SCI rats.
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.
Study Design.
A systematic review and meta-analysis.
Objective.
This study was performed to evaluate the effects of different rehabilitation interventions in spinal cord injury.
Summary of Background Data.
Several activity-based interventions have been widely applied in spinal cord injury in the past, but the effects of these rehabilitation exercises are controversial.
Methods.
Publications were searched from databases (PubMed, Embase, Cochrane, the database of the U.S. National Institutes of Health and World Health Organization International Clinical Trials Registry Platform) using the searching terms like spinal cord injury, transcranial magnetic stimulation, functional electrical stimulation, activity-based therapy, and robotic-assisted locomotor training. Randomized controlled trials and controlled trials were included. The primary outcomes included functional upper/lower extremity independence, walking capacity, spasticity, and life quality of individuals with spinal cord injury. Meta-analysis was performed using Revman 5.0 software.
Results.
Thirty-one articles were included. Meta-analysis showed that transcranial magnetic stimulation improved walking speed (95% confidence interval [CI] 0.01, 0.16) and lower extremity function (95% CI 1.55, 7.27); functional electrical stimulation significantly increased upper extremity independence (95% CI 0.37, 5.48). Robotic-assisted treadmill training improved lower extremity function (95% CI 3.44, 6.56) compared with related controls.
Conclusion.
Activity-based intervention like transcranial magnetic stimulation, functional electrical stimulation, and robotic-assisted treadmill training are effective in improving function in individuals with spinal cord injury.
Level of Evidence: 1
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.