Emerging Exosomes and Exosomal MiRNAs in Spinal Cord Injury

Abstract

Acute spinal cord injury (SCI) is a serious traumatic event to the spinal cord with considerable morbidity and mortality. This injury leads to short- and long-term variations in the spinal cord, and can have a serious effect on the patient’s sensory, motor, or autonomic functions. Due to the complicated pathological process of SCI, there is currently no successful clinical treatment strategy. Exosomes, extracellular vesicles (EVs) with a double-layer membrane structure of 30–150 nm diameter, have recently been considered as critical mediators for communication between cells and tissues by transferring proteins, lipids, and nucleic acids. Further studies verified that exosomes participate in the pathophysiological process of several diseases, including cancer, neurodegenerative diseases, and cardiovascular diseases, and could have a significant impact in their treatment. As natural carriers of biologically active cargos, exosomes have emerged as pathological mediators of SCI. In this review article, we critically discuss the functions of exosomes as intracellular mediators and potential treatments in SCI and provide an outlook on future research.

Potential of different cells-derived exosomal microRNA cargos for treating spinal cord injury

“…Moreover, when SCI occurs, the injured spinal column is hypoxic. MSCs derived exosomes, which full of phosphatase and tensin homologous small interfering RNA (ExoPTEN), can significantly enhance the angiogenesis and axon regeneration in the damaged spinal cord by reducing PTEN expression in rats [ 30 , 124 ] ( Fig. 2 ).…”

“…Importantly, exosomes could carry proteins, lipids, and RNAs to transport messages among various cell types that affect the normal physiological condition and pathological state [ 23 ]. And exosomes are capable of transporting cargoes across blood brain barrier (BBB) and blood-spinal cord barrier (BSCB) to reach distant organs without significant degradation [ 30 ]. Moreover, exosomes participate in various biological processes in SCI, including synaptic plasticity, regulating the myelin membrane biogenesis, and local delivery of proteins or nucleic acids to increasingly polarized structures [ 24 , 25 ].…”

“…There are more than 70% miRNAs expressed in the central nervous system (CNS) and been preserved in species as isochronous molecules [ 38 ]. Among the exosomal nucleic acid and silence post-transcriptional mRNA expression, exosomal miRNAs are the most critical functional substances, which are involved in cell proliferation and differentiation, immunomodulation and angiogenesis [ 30 , 39 , 40 ]. After being sorted in exosomes, the mature miRNAs can be transported to recipient cells to influence the protein network and RNA production of the recipient cells by regulating gene expression and key homeostatic processes.…”

Technological Advances of 3D Scaffold-Based Stem Cell/Exosome Therapy in Tissues and Organs

“…The SCs can restrict secondary injury, reduce inflammation, and secrete paracrine factors to protect surviving neurons. SCs also facilitate axon regeneration, and differentiate into new neurons to replace injured neurons in spinal cord injury (SCI) ( Leng et al, 2019 ; Zhang et al, 2019 ; Feng et al, 2021 ). The results of a phase I clinical trial conducted by Mendonça et al ( Mendonça et al, 2014 ) showed that administration of BMSCs improved behavioral scores, electromyography, and somatosensory evoked potentials.…”

Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Accelerate Functional Recovery After Spinal Cord Injury by Promoting the Phagocytosis of Macrophages to Clean Myelin Debris

“…Exosomes can be easily isolated and can cross the spinal cord–blood barrier and reach the injured site in the CNS system ( Yuan et al, 2019 ). Exosomes carry a large number of molecules, such as proteins and various nucleic acids [mRNAs, miRNAs, and other long non-coding RNAs (lncRNAs)] ( Feng et al, 2021 ). At present, a clinical trial of mesenchymal stem cell (MSC)-derived exosomes for the treatment of SCI has been conducted ( Nikfarjam et al, 2020 ; Lee et al, 2021 ).…”