Mesenchymal stem cell exosomes as a cell-free therapy for nerve injury-induced pain in rats.
Angiopoietin-2
/ metabolism
Animals
Calcium-Binding Proteins
/ metabolism
Cytokines
/ metabolism
Disease Models, Animal
Exosomes
/ physiology
Fibroblast Growth Factor 2
/ metabolism
Functional Laterality
Ganglia, Spinal
/ cytology
Humans
Injections, Spinal
Male
Mesenchymal Stem Cells
/ cytology
Microfilament Proteins
/ metabolism
Nerve Tissue Proteins
/ metabolism
Neuralgia
/ etiology
Peripheral Nerve Injuries
/ complications
Rats
Rats, Sprague-Dawley
Sensory Receptor Cells
/ drug effects
Vascular Endothelial Growth Factor C
/ metabolism
Journal
Pain
ISSN: 1872-6623
Titre abrégé: Pain
Pays: United States
ID NLM: 7508686
Informations de publication
Date de publication:
Jan 2019
Jan 2019
Historique:
pubmed:
7
9
2018
medline:
27
6
2019
entrez:
7
9
2018
Statut:
ppublish
Résumé
Nerve injury-induced neuropathic pain is difficult to treat. In this study, we used exosomes derived from human umbilical cord mesenchymal stem cell (UCMSC) as a cell-free therapy for nerve injury-induced pain in rats. Isolated UCMSC exosomes range in size from 30 to 160 nm and contain CD63, HSP60, and CD81 exosome markers. After L5/6 spinal nerve ligation surgery, single intrathecal injection of exosomes reversed nerve ligation-induced mechanical and thermal hypersensitivities of right hindpaw of rats at initial and well-developed pain stages. Moreover, continuous intrathecal infusion of exosomes achieved excellent preventive and reversal effects for nerve ligation-induced pain. In immunofluorescent study, lots of Exo-green-labelled exosomes could be found majorly in the ipsilateral L5 spinal dorsal horn, dorsal root ganglion, and peripheral axons, suggesting the homing ability of UCMSC exosomes. They also appeared in the central terminals or cell bodies of IB4, CGRP, and NF200 sensory neurons. In addition, exosome treatment suppressed nerve ligation-induced upregulation of c-Fos, CNPase, GFAP, and Iba1. All these data suggest that the analgesic effects of exosomes may involve their actions on neuron and glial cells. Exosomes also inhibited the level of TNF-α and IL-1β, while enhanced the level of IL-10, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor in the ipsilateral L5/6 dorsal root ganglion of nerve-ligated rats, indicating anti-inflammatory and proneurotrophic abilities. Protein analysis revealed the content of vascular endothelial growth factor C, angiopoietin-2, and fibroblast growth factor-2 in the exosomes. In summary, intrathecal infusion of exosomes from UCMSCs may be considered as a novel therapeutic approach for nerve injury-induced pain.
Identifiants
pubmed: 30188455
doi: 10.1097/j.pain.0000000000001395
pii: 00006396-201901000-00022
doi:
Substances chimiques
Aif1 protein, rat
0
Angiopoietin-2
0
Calcium-Binding Proteins
0
Cytokines
0
Microfilament Proteins
0
Nerve Tissue Proteins
0
Vascular Endothelial Growth Factor C
0
Fibroblast Growth Factor 2
103107-01-3
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
210-223Références
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