MiRNAs as Promising Translational Strategies for Neuronal Repair and Regeneration in Spinal Cord Injury

Abstract

Spinal cord injury (SCI) represents a devastating injury to the central nervous system (CNS) that is responsible for impaired mobility and sensory function in SCI patients. The hallmarks of SCI include neuroinflammation, axonal degeneration, neuronal loss, and reactive gliosis. Current strategies, including stem cell transplantation, have not led to successful clinical therapy. MiRNAs are crucial for the differentiation of neural cell types during CNS development, as well as for pathological processes after neural injury including SCI. This makes them ideal candidates for therapy in this condition. Indeed, several studies have demonstrated the involvement of miRNAs that are expressed differently in CNS injury. In this context, the purpose of the review is to provide an overview of the pre-clinical evidence evaluating the use of miRNA therapy in SCI. Specifically, we have focused our attention on miRNAs that are widely associated with neuronal and axon regeneration. “MiRNA replacement therapy” aims to transfer miRNAs to diseased cells and improve targeting efficacy in the cells, and this new therapeutic tool could provide a promising technique to promote SCI repair and reduce functional deficits.

The therapeutic potential of microRNAs to ameliorate spinal cord injury by regulating oligodendrocyte progenitor cells and remyelination

“…miRNA-based therapies face numerous challenges, including delivery, stability, and immune responses ( Hydbring and Badalian-Very, 2013 , Sun et al, 2018 ). Exposed miRNAs are difficult to be absorbed by cells due to their negative charge, off-target effect, short half-life in the systemic circulation, and rapid degradation or inactivation by abundant nucleases in the bloodstream ( Silvestro and Mazzon, 2022 ).…”

Therapeutic potential of small extracellular vesicles derived from mesenchymal stem cells for spinal cord and nerve injury

“…Relatively few studies have addressed small EVs contributions to nerve regeneration ( Figure 3 ). Studies performed to date have shown M2 macrophages, MSCs, Schwann cells, microglial, neurons, sensory neurons, motor neurons, and astrocytes secrete small EVs, and that small EVs also contain various miRNAs ( Qing et al, 2018b ; Zhang et al, 2018 ; Silvestro and Mazzon, 2022 ). Zhang et al ( Santonocito et al, 2014 ) reported that migration and proliferation were promoted when small EVs containing miR-223 were secreted by M2 macrophages co-cultured with Schwann cells and that Schwann cell migration and proliferation were reduced when they were incubated with miR-223-inhibited M2 macrophages.…”

Emerging role of non-coding RNAs in neuroinflammation mediated by microglia and astrocytes

“…Activated microglia promote secondary tissue damage in SCI. Similarly, miRNAs have been implicated in the modulation of microglial activation and polarization in SCI [ 153 ]. miR-124 is a well-studied miRNA that regulates microglial response after SCI.…”