Department of Sports Medicine, Wuxi Traditional Chinese Medicine Hospital.
Department of Clinical Laboratory, Wuxi 9th People's Hospital Affiliated to Soochow University.
Tohoku J Exp Med. 2023 Feb 28;259(3):237-246. doi: 10.1620/tjem.2022.J118. Epub 2022 Dec 29.
Bone marrow mesenchymal stem cell (BMMSC) is reported to promote spinal cord injury (SCI) recovery via secreting exosomes to deliver RNAs, proteins, lipids, etc. The present study aimed to investigate the effect of microRNA 137 (miR-137)-overexpressing BMMSC exosomes on SCI rats. BMMSCs were extracted from Sprague-Dawley (SD) rat hind leg bone marrow, and then BMMSC-secreted exosomes were collected. MiR-137 mimic and negative control (NC) mimic were transfected into BMMSCs, and then the corresponding exosomes were collected. Subsequently, SD rats were treated with sham operation + phosphate-buffered saline (PBS), SCI operation + PBS, SCI operation + NC mimic BMMSC exosomes, or SCI operation + miR-137-overexpressing BMMSC exosomes. MiR-137 was downregulated in the spinal cord tissue of SCI rats compared to sham rats. Furthermore, BMMSC exosome injection elevated the Basso, Beattie, and Bresnahan (BBB) scores and neuronal viability and reduced tissue injury and proinflammatory cytokine expression in the spinal cord tissue of SCI rats compared to PBS treatment. Subsequently, miR-137-overexpressing BMMSC exosome injection improved the BBB score and neuron viability, and decreased tissue injury as well as proinflammatory cytokine expression in SCI rats compared to NC-overexpressing BMMSC exosomes. Additionally, miR-137-overexpressing BMMSC exosomes also diminished neuronal apoptosis in the spinal cord tissue of SCI rats compared to NC-overexpressing BMMSC exosomes. In conclusion, miR-137-overexpressing BMMSC exosomes reduce tissue injury and inflammation while improving locomotor capacity and neuronal viability in SCI rats. These findings suggest that miR-137-overexpressing BMMSC exosomes may serve as a treatment option for SCI recovery.
骨髓间充质干细胞（BMMSC）通过分泌外泌体来传递 RNA、蛋白质、脂质等，被报道可促进脊髓损伤（SCI）的恢复。本研究旨在探讨过表达微小 RNA 137（miR-137）的 BMMSC 外泌体对 SCI 大鼠的影响。从 Sprague-Dawley（SD）大鼠后腿骨髓中提取 BMMSC，然后收集 BMMSC 分泌的外泌体。将 miR-137 模拟物和阴性对照（NC）模拟物转染到 BMMSC 中，然后收集相应的外泌体。随后，SD 大鼠接受假手术+磷酸盐缓冲液（PBS）、SCI 手术+PBS、SCI 手术+NC 模拟物 BMMSC 外泌体或 SCI 手术+miR-137 过表达 BMMSC 外泌体治疗。与 sham 大鼠相比，SCI 大鼠脊髓组织中 miR-137 下调。此外，与 PBS 处理相比，BMMSC 外泌体注射可提高 Basso、Beattie 和 Bresnahan（BBB）评分和神经元活力，减少 SCI 大鼠脊髓组织损伤和促炎细胞因子表达。随后，与 NC 过表达 BMMSC 外泌体相比，miR-137 过表达 BMMSC 外泌体注射可改善 SCI 大鼠的 BBB 评分和神经元活力，并降低组织损伤和促炎细胞因子表达。此外，与 NC 过表达 BMMSC 外泌体相比，miR-137 过表达 BMMSC 外泌体还可减少 SCI 大鼠脊髓组织中的神经元凋亡。综上所述，miR-137 过表达 BMMSC 外泌体可减轻 SCI 大鼠的组织损伤和炎症，同时提高运动能力和神经元活力。这些发现表明，miR-137 过表达 BMMSC 外泌体可能成为 SCI 恢复的一种治疗选择。
