2025, Vol. 29 ›› Issue (36): 7827-7838

Action mechanism of mesenchymal stem cell-derived exosomes carrying miRNAs in improving spinal cord injury

Guo Jia1, 2, Ren Yafeng2, Li Bing2, Huang Jing1, Shang Wenya1, Yang Yike1, Liu Huiyao1   

Abstract: BACKGROUND: Currently, spinal cord injury imposes a huge psychological and economic burden on patients and the National Health Service. The prevention, treatment, and rehabilitation of spinal cord injury have become an important topic in the field of medicine. Therefore, it is important to explore new effective therapeutic strategies based on an in-depth understanding of the underlying molecular mechanisms of spinal cord injury.
OBJECTIVE: To review the research progress on the mechanism of action of mesenchymal stem cell-derived exosomes loaded with various miRNAs in improving the function of spinal cord injury, and based on the current status of clinical translation, to put forward a few thoughts and outlooks on their clinical use.  
METHODS: The first author searched CNKI and PubMed databases using “mesenchymal stem cells, exosomes, spinal cord injury, miRNA, pathophysiology, clinical translation, clinical trials, good manufacturing practice” as Chinese and English search terms. The types of literature included treatises and reviews, and the language types were English and Chinese. Finally, 72 papers were screened and analyzed.
RESULTS AND CONCLUSION: (1) This article outlines the biological properties of exosomes and the advantages that they can serve as good vectors for loading miRNAs. A variety of miRNAs mediated by mesenchymal stem cell-derived exosomes mainly promote the recovery of neuronal function by regulating the expression of nerve regeneration-associated proteins, repressing RAS homologous gene family member A, activating cyclophosphoadenosine effector-binding proteins, and signaling and transcriptional activation proteins 3, and regulating phosphoinositide and tensin homologue/programmed cell death factor 4 pathways. Inflammatory responses were improved by regulating endoplasmic reticulum-to-nucleus signaling 1, expression of interferon regulatory factor 5, Toll-like receptor 4/nuclear factor-kappa B pathway, and down-regulating related pro-inflammatory factors. Angiogenesis was promoted by inhibition of germination-associated domain 1-containing EVH1 and phosphatidylinositol 3-kinase regulatory subunit 2. (2) Further comparative analyses revealed that miR-216-5p, miR-145-5p, and miR-146b improved inflammatory responses by regulating related pathways. Combining these miRNAs may produce more significant effects; hypoxic preconditioning may be a preconditioning method to increase the efficacy of exosomal therapy. (3) There are currently no clinical trials applying mesenchymal stem cell-derived exosomes to spinal cord injury, which is related to the need to meet good manufacturing practices before they can be put into clinical use. Challenges such as the need for large-scale, high-volume cell production, the lack of an efficient and uniform method for isolating exosomes, and the need to pass a strict regulatory approval mechanism prior to clinical use have impeded the clinical entry. (4) miRNAs have great potential as exosomal contents of mesenchymal stem cells in the treatment of spinal cord injury, and their mechanism of action should be explored in depth as well as accelerated to the clinical trial stage in order to provide a new and effective method for the treatment of spinal cord injury.

Key words: spinal cord injury, mesenchymal stem cell, exosomes, miRNA, pathophysiology, clinical translation, clinical trial, good manufacturing practice