The Role of Exosomes and Exosomal Noncoding RNAs From Different Cell Sources in Spinal Cord Injury

Abstract

Spinal cord injury (SCI) not only affects the quality of life of patients but also poses a heavy burden on their families. Therefore, it is essential to prevent the occurrence of SCI; for unpreventable SCI, it is critical to develop effective treatments. In recent years, various major breakthroughs have been made in cell therapy to protect and regenerate the damaged spinal cord via various mechanisms such as immune regulation, paracrine signaling, extracellular matrix (ECM) modification, and lost cell replacement. Nevertheless, many recent studies have shown that the cell therapy has many disadvantages, such as tumorigenicity, low survival rate, and immune rejection. Because of these disadvantages, the clinical application of cell therapy is limited. In recent years, the role of exosomes in various diseases and their therapeutic potential have attracted much attention. The same is true for exosomal noncoding RNAs (ncRNAs), which do not encode proteins but affect transcriptional and translational processes by targeting specific mRNAs. This review focuses on the mechanism of action of exosomes obtained from different cell sources in the treatment of SCI and the regulatory role and therapeutic potential of exosomal ncRNAs. This review also discusses the future opportunities and challenges, proposing that exosomes and exosomal ncRNAs might be promising tools for the treatment of SCI.

Remyelinating effect driven by transferrin‐loaded extracellular vesicles

“…In this context, studies were conducted on the use of EVs as carriers of biomolecules that can efficiently deliver Tf, protecting the cargo from degradation while reducing immunogenicity (Haney et al, 2015; Luan et al, 2017; Wiklander et al, 2015; Yang et al, 2022). In previous work, we employed two passive cargo‐loading strategies which rendered successful EV loading with Tf, specifically through binding to its receptor TfR1, present in the EV membrane (Mattera et al, 2020).…”

Recent advances in endogenous neural stem/progenitor cell manipulation for spinal cord injury repair

“…Exosomes, the smallest extracellular membranous vesicles (~30-150 nm), contain nucleic acids (e.g., DNA, mRNA, noncoding RNA), proteins (e.g., CD63/CD81/CD9, HSP60/HSP70/HSPA5/CCT2/ HSP90, TSG101, AIP1/ALIX), and lipids (e.g., cholesterol, phosphatidylserine, phosphatidylinositol), suggesting a critical role in cell-cell communication [87]. NSPC-secreted exosomes (SC-Exos) can exert neurogenic, neurotrophic, anti-apoptotic, and anti-inflammatory effects while avoiding the limitations of the original stem cells, such as tumorigenicity, thrombogenicity, and immunogenicity [88]. A retrospective study based on animal SCI models indicated that SC-Exos derived from different stem cells increased the expression of anti-inflammatory factors (IL-4, IL-10) and anti-apoptotic protein Bcl-2, and reduced the levels of pro-inflammatory factors (IL-1β, TNF-α) and apoptotic protein BAX, thus improving the motor function recovery [89].…”

The role of exosomes in central nervous system tissue regeneration and repair

“…Cell therapy has made breakthroughs in the treatment of SCI in recent years. However, due to its tumorigenicity and low survival rate at the time of treatment, it still has some limitations in clinical application [46]. Exosome-mediated therapy can inhibit the synthesis of some proteins in the body that prevent SCI recovery and promote the regeneration of some cells to restore body function.…”