Schwann cells-derived exosomes promote functional recovery after spinal cord injury by promoting angiogenesis

被引:26
作者
Huang, Jiang-Hu [1 ]
Chen, Yong-Neng [1 ]
He, Hang [1 ]
Fu, Chun-Hui [2 ]
Xu, Zhao-Yi [1 ]
Lin, Fei-Yue [1 ]
机构
[1] Fujian Med Univ, Fujian Prov Hosp, Dept Orthoped, Fuzhou, Peoples R China
[2] Fuzhou Maixin Biotech Co Ltd, Fuzhou, Peoples R China
关键词
Schwann cells; exosomes; angiogenesis; integrin-beta; 1; spinal cord injury; BETA-1-INTEGRINS; TRANSPLANTATION; REGENERATION; REPAIR;
D O I
10.3389/fncel.2022.1077071
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Exosomes are small vesicles that contain diverse miRNA, mRNA, and proteins that are secreted by multiple cells, and play a vital function in cell-cell communication. Numerous exosomes produced by cells have been demonstrated to be protective against spinal cord injury (SCI). This study aims to investigate the neuroprotective effect of Schwann cells-derived exosomes (SCs-Exos) on spinal cord injury. We found that SCs-Exos can be taken directly by brain-derived endothelial cells.3 (bEnd.3 cells) and promoted to proliferate, migrate, and form bEnd.3 tube. Additionally, our results showed that the pro-angiogenesis molecules, Integrin-beta 1, were highly expressed in SCs-Exos. Moreover, we used special shRNA technology to investigate the role of Integrin-beta 1 in mediating the effect of SCs-Exos-induced angiogenesis on bEnd.3 cells. We observed that the pro-angiogenic effect of SCs-Exos on bEnd.3 cells was suppressed by inhibiting the expression of integrin-beta 1 in SCs-Exos. In the SCI model, we found that SCs-Exos attenuated tissue damage and improved functional recovery after SCI. Using immunofluorescence staining, we observed that SCs-Exos treatment promoted angiogenesis in SCI, and integrin-beta 1 was required to promote angiogenesis. In conclusion, our results indicate that SCs-Exos promote angiogenesis by delivering integrin-beta 1 and may serve as a promising novel therapeutic agent for enhancing neurological functional recovery after SCI.
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页数:14
相关论文
共 33 条
[1]   Schwann Cell-Derived Exosomes Enhance Axonal Regeneration in the Peripheral Nervous System [J].
Alejandra Lopez-Verrilli, Maria ;
Picou, Frederic ;
Court, Felipe A. .
GLIA, 2013, 61 (11) :1795-1806
[2]   Cell transplantation therapy for spinal cord injury [J].
Assinck, Peggy ;
Duncan, Greg J. ;
Hilton, Brett J. ;
Plemel, Jason R. ;
Tetzlaff, Wolfram .
NATURE NEUROSCIENCE, 2017, 20 (05) :637-647
[3]   A SENSITIVE AND RELIABLE LOCOMOTOR RATING-SCALE FOR OPEN-FIELD TESTING IN RATS [J].
BASSO, DM ;
BEATTIE, MS ;
BRESNAHAN, JC .
JOURNAL OF NEUROTRAUMA, 1995, 12 (01) :1-21
[4]   Exosomes: A New Weapon to Treat the Central Nervous System [J].
Braccioli, Luca ;
van Velthoven, Cindy ;
Heijnen, Cobi J. .
MOLECULAR NEUROBIOLOGY, 2014, 49 (01) :113-119
[5]   Three Dimensional Quantification of Microarchitecture and Vessel Regeneration by Synchrotron Radiation Microcomputed Tomography in a Rat Model of Spinal Cord Injury [J].
Cao, Yong ;
Zhou, Yuan ;
Ni, Shuangfei ;
Wu, Tianding ;
Li, Ping ;
Liao, Shenghui ;
Hu, Jianzhong ;
Lu, Hongbin .
JOURNAL OF NEUROTRAUMA, 2017, 34 (06) :1187-1199
[6]  
Carlson Gregory D, 2002, Spine J, V2, P116, DOI 10.1016/S1529-9430(01)00029-8
[7]   Commentary on the prevention of paralysis after traumatic spinal cord injury in humans: the neglected factor - urgent restoration of spinal cord circulation [J].
Crock, HV ;
Yoshizawa, H ;
Yamagishi, M ;
Crock, MC .
EUROPEAN SPINE JOURNAL, 2005, 14 (09) :910-914
[8]   Schwann cell transplantation and descending propriospinal regeneration after spinal cord injury [J].
Deng, Ling-Xiao ;
Walker, Chandler ;
Xu, Xiao-Ming .
BRAIN RESEARCH, 2015, 1619 :104-114
[9]   Exosome-mediated Delivery of Hydrophobically Modified siRNA for Huntingtin mRNA Silencing [J].
Didiot, Marie-Cecile ;
Hall, Lauren M. ;
Coles, Andrew H. ;
Haraszti, Reka A. ;
Godinho, Bruno M. D. C. ;
Chase, Kathryn ;
Sapp, Ellen ;
Ly, Socheata ;
Alterman, Julia F. ;
Hassler, Matthew R. ;
Echeverria, Dimas ;
Raj, Lakshmi ;
Morrissey, David V. ;
DiFiglia, Marian ;
Aronin, Neil ;
Khvorova, Anastasia .
MOLECULAR THERAPY, 2016, 24 (10) :1836-1847
[10]  
Dreyer F, 2016, METHODS MOL BIOL, V1448, P201, DOI 10.1007/978-1-4939-3753-0_15