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Exosomes Derived From Bone Marrow Mesenchymal Stem Cells Inhibit Complement Activation In Rats With Spinal Cord Injury

Authors Zhao C, Zhou X, Qiu J, Xin D, Li T, Chu X, Yuan H, Wang H, Wang Z, Wang D

Received 22 March 2019

Accepted for publication 3 October 2019

Published 24 October 2019 Volume 2019:13 Pages 3693—3704

DOI https://doi.org/10.2147/DDDT.S209636

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 2

Editor who approved publication: Dr Georgios D. Panos


Chuanliang Zhao,1–3 Xin Zhou,1,2 Jie Qiu,1,2 Danqing Xin,2 Tingting Li,2 Xili Chu,2 Hongtao Yuan,2 Haifeng Wang,1 Zhen Wang,2 Dachuan Wang1

1Department of Spinal Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Physiology, Shandong University School of Basic Medical Sciences, Jinan, Shandong, People’s Republic of China; 3Department of Orthopedic, Feicheng Hospital of Traditional Chinese Medicine, Feicheng, Shandong, People’s Republic of China

Correspondence: Dachuan Wang
Department of Spinal Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, People’s Republic of China
Tel +86 139 5316 9759
Email wangdachuan@medmail.com.cn

Purpose: Spinal cord injury (SCI) is a relatively common, devastating traumatic condition resulting in permanent disability. In this study, the use of exosomes derived from bone mesenchymal stem cells (BMSCs-Exo) as a cell-free therapy for the treatment of SCI in rats was investigated to gain insights into their mechanisms of action.
Methods: Rats were randomly divided into three groups, Sham (treated with PBS), SCI (SCI injury + PBS) and SCI + Exo (SCI injury + BMSCs-Exo). Changes in the complement system between the three groups were assessed with the use of proteomics. The proteomic data were verified using reverse transcription-polymerase chain reaction (RT-PCR). In addition, the distributions of BMSCs-Exo in rats with SCI were detected by immunofluorescence. Moreover, SCI-activated NF-κB levels were determined using Western blot.
Results: SCI insult increased complement levels, including C4, C5, C6, C4 binding protein alpha and complement factor H. In contrast, the SCI + BMSCs-Exo group exhibited attenuated SCI-induced complement levels. Immunofluorescence assay results revealed that BMSCs-Exo mainly accumulated at the spinal cord injury site and were bound to microglia cells. Western blot analysis of tissue lysates showed that BMSCs-Exo treatment also inhibited SCI-activated nuclear factor kappa-B (NF-κB).
Conclusion: BMSCs-Exo play a protective role in spinal cord injury by inhibiting complement mRNA synthesis and release and by inhibiting SCI-activated NF-κB by binding to microglia.

Keywords: exosomes, proteomics, complement, spinal cord injury

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