Alleviation of Spinal Cord Injury by MicroRNA 137-Overexpressing Bone Marrow Mesenchymal Stem Cell-Derived Exosomes

Alleviation of Spinal Cord Injury by MicroRNA 137-Overexpressing Bone Marrow Mesenchymal Stem Cell-Derived Exosomes

Yang Shao,¹ Qiubo Wang,² Lei Liu,¹ Jianwei Wang³ and Mao Wu⁴

¹Department of Sports Medicine, Wuxi Traditional Chinese Medicine Hospital, Wuxi, Jiangsu, China
²Department of Clinical Laboratory, Wuxi 9th People’s Hospital Affiliated to Soochow University, Wuxi, Jiangsu, China
³Department of Joint Orthopedics, Wuxi Traditional Chinese Medicine Hospital, Wuxi, Jiangsu, China
⁴Department of Traumatic Orthopedics, Wuxi Traditional Chinese Medicine Hospital, Wuxi, Jiangsu, China

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.

Keywords —— bone marrow mesenchymal stem cells; exosome; microRNA 137; rat; spinal cord injury

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Tohoku J. Exp. Med 2023, 259, 237-246.

Correspondence: Mao Wu, Department of Traumatic Orthopedics, Wuxi Traditional Chinese Medicine Hospital, No. 8 Zhongnan West Road, Wuxi, Jiangsu 214071, China.

e-mail: fsyy01157@njucm.edu.cn

Correspondence: Wang, Department of Joint Orthopedics, Wuxi Traditional Chinese Medicine Hospital, No. 8 Zhongnan West Road, Wuxi Jiangsu, 214071, China.

e-mail: wangjianwei1963@126.com