Abstract
Spinal cord injury (SCI) is a life-threatening condition that leads to permanent disability with partial or complete loss of motor, sensory, and autonomic functions. SCI is usually caused by initial mechanical insult, followed by a cascade of several neuroinflammation and structural changes. For ameliorating the neuroinflammatory cascades, MSC has been regarded as a therapeutic agent. The animal SCI research has demonstrated that MSC can be a valuable therapeutic agent with several growth factors and cytokines that may induce anti-inflammatory and regenerative effects. However, the therapeutic efficacy of MSCs in animal SCI models is inconsistent, and the optimal method of MSCs remains debatable. Moreover, there are several limitations to developing these therapeutic agents for humans. Therefore, identifying novel agents for regenerative medicine is necessary. Extracellular vesicles are a novel source for regenerative medicine; they possess nucleic acids, functional proteins, and bioactive lipids and perform various functions, including damaged tissue repair, immune response regulation, and reduction of inflammation. MSC-derived exosomes have advantages over MSCs, including small dimensions, low immunogenicity, and no need for additional procedures for culture expansion or delivery. Certain studies have demonstrated that MSC-derived extracellular vesicles (EVs), including exosomes, exhibit outstanding chondroprotective and anti-inflammatory effects. Therefore, we reviewed the principles and patho-mechanisms and summarized the research outcomes of MSCs and MSC-derived EVs for SCI, reported to date.
Highlights
Spinal cord injury (SCI) is a life-threatening, devastating injury to the spinal cord, leading to temporary or permanent changes to the cord, accompanied by partial or complete loss of motor, sensory, and autonomic functions [1,2]
These findings suggest that extracellular vesicles (EVs) possess many affirmative factors for the regeneration of injured spinal cords and, in the near future, may be a novel therapeutic agent for SCI in humans
Owing to the complex and long-term pathological process of SCI, recovery of the injured spinal cord is hampered by various factors
Summary
Spinal cord injury (SCI) is a life-threatening, devastating injury to the spinal cord, leading to temporary or permanent changes to the cord, accompanied by partial or complete loss of motor, sensory, and autonomic functions [1,2]. Neuroinflammation is characterized by the activation of local resident immune cells, and this activation is arbitrated by a protein complex-inflammasome called the nucleotidebinding domain-like receptor protein 3 (NLRP3) inflammasome This inflammasome plays a very important role in SCI secondary injuries [78]. Animal experimental models have shown that the NLRP3 inflammasome may be triggered and up-regulated following SCI and that inhibition of the NLRP3 inflammasome promotes functional recovery after SCI [81–85] Both classic and alternative complement pathways in the local immune response can be activated after SCI [86]. It has recently been shown that reactive astrocytes eliminate red blood cells (RBCs) around SCI lesions through phagocytosis This mechanism, named the astrocytic erythrophagocytosis, is considered to contribute to the rapid removal of scattered RBCs around the injured site to prevent macrophage aggregation and associated destructive inflammation. Hu et al reported that miRNA-126 expression decreases after SCI, whereas increasing miRNA-126 levels appear to reduce inflammation and promote angiogenesis and functional recovery [106]
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