Chinese Journal of Tissue Engineering Research ›› 2019, Vol. 23 ›› Issue (21): 3294-3301.doi: 10.3969/j.issn.2095-4344.1760

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Bone marrow mesenchymal stem cell-derived exosomes reduce the activation of type A1 astrocytes after spinal cord injury

Zhou Yan1, Wang Lin2, Pei Shuang2, Li Yanfei2, Chen Xuemei3, Jia Yanjie2   

  1. 1Department of Radiology, 2Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China; 3Department of Human Anatomy, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China
  • Revised:2019-02-01 Online:2019-07-28 Published:2019-07-28
  • Contact: Jia Yanjie, MD, Doctoral supervisor, Professor, Chief physician, Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
  • About author:Zhou Yan, Master, Lecturer, Department of Radiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
  • Supported by:

    the National Natural Science Foundation of China, No. U1604170 (to JYJ)

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Abstract:

BACKGROUND: Previous studies found that exosomes from bone marrow mesenchymal stem cells could reduce the number of reactive astrocytes after spinal cord injury, thereby improving post-injury motor function.
OBJECTIVE: To explore the role of bone marrow mesenchymal stem cell-derived exosomes in the activation of A1 astrocytes as well as in the repair of spinal cord injury. 
METHODS: Bone marrow mesenchymal stem cells from Sprague-Dawely rats were cultured, and then the exosomes from the cell supernatant were extracted and identified by ultracentrifugation. Eighty adult male Sprague-Dawley rats were randomly divided into sham operation group, spinal cord injury group (model group), bone marrow mesenchymal stem cell group (cell transplantation group) and exosome group (n=20/group). Except the sham operation group, an animal model of spinal cord injury was made in all the groups by Allen method. Two hours postoperatively, the equal volume of PBS, bone marrow mesenchymal stem cell suspension or bone marrow mesenchymal stem cell-derived exosome suspension was injected through the tail vein respectively, every 3 days, for three sessions. Basso, Beattie and Bresnahan scoring for motor function of the hind limb was performed preoperatively and and 1, 3, 7, 14, 28 days postoperatively. Hematoxylin-eosin staining and transmission electron microscope were used to observe the morphology of spinal cord tissue at 7 days postoperatively. Immunofluorescence staining was used to detect the number of A1 astrocytes, NeuN positive neurons and Caspase-3 positive apoptotic cells. ELISA assay was used to detect the levels of tumor necrosis factor-α and interleukin-1α in the spinal cord tissue. Western blot assay was used to determine relative protein expression levels of C3 and GFAP.
RESULTS AND CONCLUSION: Exosomes from bone marrow mesenchymal stem cells showed a saucer-like appearance under transmission electron microscope, expressing exosome markers CD63 and CD9. The exosomes reduced inflammatory cell infiltration of spinal cord tissue, reduced myelin degeneration and axonal degeneration, reduced the expression levels of tumor necrosis factor-α, interleukin-1α and C3, reduced the number of A1 astrocytes, and reduced cell apoptosis, but increased the number of residual neurons, and improved limb motor function. To conclude, exosomes from bone marrow mesenchymal stem cells can reduce the activation of type A1 astrocytes in the spinal cord and promote the recovery of motor function after spinal cord injury.

Key words: spinal cord injury, bone marrow mesenchymal stem cells, exosomes, type A1 astrocytes, inflammatory factors, motor function, National Natural Science Foundation of China

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