Biocompatible exosome-modified fibrin gel accelerates the recovery of spinal cord injury by VGF-mediated oligodendrogenesis

Abstract Exosomes show potential for treating patients with spinal cord injury (SCI) in clinical practice, but the underlying repair mechanisms remain poorly understood, and biological scaffolds available for clinical transplantation of exosomes have yet to be explored. In the present study, we demo...

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Main Authors: Xiaolie He, Li Yang, Kun Dong, Feng Zhang, Yuchen Liu, Bei Ma, Youwei Chen, Jian Hai, Rongrong Zhu, Liming Cheng
Format: Article
Language:English
Published: BMC 2022-08-01
Series:Journal of Nanobiotechnology
Subjects:
Online Access:https://doi.org/10.1186/s12951-022-01541-3
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author Xiaolie He
Li Yang
Kun Dong
Feng Zhang
Yuchen Liu
Bei Ma
Youwei Chen
Jian Hai
Rongrong Zhu
Liming Cheng
author_facet Xiaolie He
Li Yang
Kun Dong
Feng Zhang
Yuchen Liu
Bei Ma
Youwei Chen
Jian Hai
Rongrong Zhu
Liming Cheng
author_sort Xiaolie He
collection DOAJ
description Abstract Exosomes show potential for treating patients with spinal cord injury (SCI) in clinical practice, but the underlying repair mechanisms remain poorly understood, and biological scaffolds available for clinical transplantation of exosomes have yet to be explored. In the present study, we demonstrated the novel function of Gel-Exo (exosomes encapsulated in fibrin gel) in promoting behavioural and electrophysiological performance in mice with SCI, and the upregulated neural marker expression in the lesion site suggested enhanced neurogenesis by Gel-Exo. According to the RNA-seq results, Vgf (nerve growth factor inducible) was the key regulator through which Gel-Exo accelerated recovery from SCI. VGF is related to myelination and oligodendrocyte development according to previous reports. Furthermore, we found that VGF was abundant in exosomes, and Gel-Exo-treated mice with high VGF expression indeed showed increased oligodendrogenesis. VGF was also shown to promote oligodendrogenesis both in vitro and in vivo, and lentivirus-mediated VGF overexpression in the lesion site showed reparative effects equal to those of Gel-Exo treatment in vivo. These results suggest that Gel-Exo can thus be used as a biocompatible material for SCI repair, in which VGF-mediated oligodendrogenesis is the vital mechanism for functional recovery.
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spelling doaj.art-54b538dadd814b0282ce4a2bbad3fe092022-12-22T04:05:13ZengBMCJournal of Nanobiotechnology1477-31552022-08-0120111710.1186/s12951-022-01541-3Biocompatible exosome-modified fibrin gel accelerates the recovery of spinal cord injury by VGF-mediated oligodendrogenesisXiaolie He0Li Yang1Kun Dong2Feng Zhang3Yuchen Liu4Bei Ma5Youwei Chen6Jian Hai7Rongrong Zhu8Liming Cheng9Orthopaedics Department of Tongji Hospital, Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, School of Medicine, School of Life Sciences and Technology, Tongji UniversityOrthopaedics Department of Tongji Hospital, Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, School of Medicine, School of Life Sciences and Technology, Tongji UniversityOrthopaedics Department of Tongji Hospital, Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, School of Medicine, School of Life Sciences and Technology, Tongji UniversityOrthopaedics Department of Tongji Hospital, Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, School of Medicine, School of Life Sciences and Technology, Tongji UniversityOrthopaedics Department of Tongji Hospital, Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, School of Medicine, School of Life Sciences and Technology, Tongji UniversityOrthopaedics Department of Tongji Hospital, Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, School of Medicine, School of Life Sciences and Technology, Tongji UniversityOrthopaedics Department of Tongji Hospital, Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, School of Medicine, School of Life Sciences and Technology, Tongji UniversityOrthopaedics Department of Tongji Hospital, Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, School of Medicine, School of Life Sciences and Technology, Tongji UniversityOrthopaedics Department of Tongji Hospital, Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, School of Medicine, School of Life Sciences and Technology, Tongji UniversityOrthopaedics Department of Tongji Hospital, Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, School of Medicine, School of Life Sciences and Technology, Tongji UniversityAbstract Exosomes show potential for treating patients with spinal cord injury (SCI) in clinical practice, but the underlying repair mechanisms remain poorly understood, and biological scaffolds available for clinical transplantation of exosomes have yet to be explored. In the present study, we demonstrated the novel function of Gel-Exo (exosomes encapsulated in fibrin gel) in promoting behavioural and electrophysiological performance in mice with SCI, and the upregulated neural marker expression in the lesion site suggested enhanced neurogenesis by Gel-Exo. According to the RNA-seq results, Vgf (nerve growth factor inducible) was the key regulator through which Gel-Exo accelerated recovery from SCI. VGF is related to myelination and oligodendrocyte development according to previous reports. Furthermore, we found that VGF was abundant in exosomes, and Gel-Exo-treated mice with high VGF expression indeed showed increased oligodendrogenesis. VGF was also shown to promote oligodendrogenesis both in vitro and in vivo, and lentivirus-mediated VGF overexpression in the lesion site showed reparative effects equal to those of Gel-Exo treatment in vivo. These results suggest that Gel-Exo can thus be used as a biocompatible material for SCI repair, in which VGF-mediated oligodendrogenesis is the vital mechanism for functional recovery.https://doi.org/10.1186/s12951-022-01541-3ExosomesFibrin gelSpinal cord injuryVGFOligodendrogenesis
spellingShingle Xiaolie He
Li Yang
Kun Dong
Feng Zhang
Yuchen Liu
Bei Ma
Youwei Chen
Jian Hai
Rongrong Zhu
Liming Cheng
Biocompatible exosome-modified fibrin gel accelerates the recovery of spinal cord injury by VGF-mediated oligodendrogenesis
Journal of Nanobiotechnology
Exosomes
Fibrin gel
Spinal cord injury
VGF
Oligodendrogenesis
title Biocompatible exosome-modified fibrin gel accelerates the recovery of spinal cord injury by VGF-mediated oligodendrogenesis
title_full Biocompatible exosome-modified fibrin gel accelerates the recovery of spinal cord injury by VGF-mediated oligodendrogenesis
title_fullStr Biocompatible exosome-modified fibrin gel accelerates the recovery of spinal cord injury by VGF-mediated oligodendrogenesis
title_full_unstemmed Biocompatible exosome-modified fibrin gel accelerates the recovery of spinal cord injury by VGF-mediated oligodendrogenesis
title_short Biocompatible exosome-modified fibrin gel accelerates the recovery of spinal cord injury by VGF-mediated oligodendrogenesis
title_sort biocompatible exosome modified fibrin gel accelerates the recovery of spinal cord injury by vgf mediated oligodendrogenesis
topic Exosomes
Fibrin gel
Spinal cord injury
VGF
Oligodendrogenesis
url https://doi.org/10.1186/s12951-022-01541-3
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