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2022, Vol. 26 ›› Issue (7): 992-998

Exosomes derived from bone marrow mesenchymal stem cells improve the integrity of the blood-spinal cord barrier after spinal cord injury

Hu Wei, Xie Xingqi, Tu Guanjun   

  1. Department of Orthopedics, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China

  • Received:2021-02-09 Revised:2021-02-20 Accepted:2021-03-24 Online:2022-03-08 Published:2021-10-29

  • Contact: Tu Guanjun, MD, Professor, Chief physician, Department of Orthopedics, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China

  • About author:Hu Wei, Master candidate, Department of Orthopedics, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China

  • Supported by:

    the Guidance Program of the Natural Science Foundation of Liaoning Province, No. 201602857 (to TGJ)



Abstract: BACKGROUND: The studies reveal that stem cells-derived exosomes promote locomotor recovery after spinal cord injury.
OBJECTIVE: To investigate whether the bone marrow mesenchymal stem cells-derived exosomes promote locomotor recovery via inhibiting the damage of the blood-spinal cord barrier.
METHODS: Sixty Sprague-Dawley rats were randomly divided into sham operation group, model group, and exosome group (n=20). The rat models of spinal cord injury were established by modified Allen’s method. In the exosome group, 200 μL of bone marrow mesenchymal stem cells-derived exosomes were injected through the tail vein at 30 minutes and 1 day after injury. On the third day after injury, the permeability of the blood-spinal cord barrier was observed. Western blot assay was used to detect the expression of matrix metalloproteinase-9 and claudin-5, Occludin and ZO-1. Gelatin zymography was used to detect the activity of matrix metalloproteinase-9. Immunofluorescence was used to detect the infiltration of neutrophils. Hematoxylin-eosin staining was used to observe the morphological changes of spinal cord injury. At 1, 3, 5, 7, 10, 14, and 21 days after injury, the Basso-Beattie-Bresnahan rating scale was used to evaluate the recovery of motor function.   

RESULTS AND CONCLUSION: (1) The Basso-Beattie-Bresnahan scores of rats treated with exosome were significantly higher than these spinal cord injury rats at 10, 14, and 21 days after spinal cord injury (P < 0.05). The results of hematoxylin-eosin staining showed that the damage area in the exosome group was significantly reduced compared to the model group (P < 0.05). (2) Exosome treatment significantly reduced the amount of Evans Blue dye extravasation (P < 0.05). Compared with the model group, the expression levels of tight junction protein, including claudin-5, Occludin and ZO-1, were significantly increased in the exosome group (P < 0.05). (3) Exosome inhibited matrix metalloproteinase-9 expression and activity (P < 0.05). (4) Infiltrated myeloperoxidase-positive neutrophils were observed at the lesion site of injured spinal cord at 3 days after spinal cord injury. The exosome treatment significantly inhibited the infiltration of neutrophils (P < 0.05). (5) The results suggested that bone marrow mesenchymal stem cells-derived exosome improved functional recovery after spinal cord injury in part by inhibiting blood-spinal cord barrier disruption and the subsequent infiltration of neutrophils through reducing the degradation of tight junction proteins by inhibiting the expression and activity of matrix metalloproteinase-9.

Key words:stem cell, bone marrow mesenchymal stem cell, exosome, spinal cord injury, blood-spinal cord barrier, matrix metalloprotease-9, tight junction protein, neutrophil


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