Intravenous administration of human mesenchymal stem cells derived from adipose tissue and umbilical cord improves neuropathic pain via suppression of neuronal damage and anti-inflammatory actions in rats.
Activating Transcription Factor 3
/ metabolism
Adipose Tissue
/ cytology
Animals
Calcium-Binding Proteins
/ metabolism
Disease Models, Animal
Ganglia, Spinal
/ immunology
Humans
Macrophages
/ cytology
Male
Mesenchymal Stem Cell Transplantation
Mesenchymal Stem Cells
/ cytology
Microfilament Proteins
/ metabolism
Neuralgia
/ therapy
Neurons
/ metabolism
Rats
Rats, Sprague-Dawley
Sciatic Nerve
/ metabolism
Umbilical Cord
/ cytology
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2022
2022
Historique:
received:
23
12
2020
accepted:
07
01
2022
entrez:
14
2
2022
pubmed:
15
2
2022
medline:
3
3
2022
Statut:
epublish
Résumé
Mesenchymal stem cells (MSCs), which are isolated from adipose tissue (AD-MSCs), umbilical cord (UC-MSCs), or bone marrow, have therapeutic potential including anti-inflammatory and immunomodulatory activities. It was recently reported that MSCs are also effective as a therapeutic treatment for neuropathic pain, although the underlying mechanisms have yet to be resolved. Therefore, in this study, we investigated the effects of human AD- and UC-MSCs on neuropathic pain and its mechanisms using rat models of partial sciatic nerve ligation (PSNL). AD- or UC-MSCs were intravenously administered 4 days after PSNL. Antinociceptive effects were then evaluated using the von Frey and weight-bearing tests. We found that, 3-9 days after the administration of AD- or UC-MSCs to PSNL-exposed rats, both the mechanical threshold and differences in weight-bearing of the right and left hind paws were significantly improved. To reveal the potential underlying antinociceptive mechanisms of MSCs, the levels of activation transcription factor 3- and ionized calcium-binding adapter molecule 1-positive cells were measured by immunohistochemical analysis. AD- and UC-MSCs significantly decreased the levels of these proteins that were induced by PSNL in the dorsal root ganglia. Additionally, UC-MSC significantly improved the PSNL-induced decrease in the myelin basic protein level in the sciatic nerve, indicating that UC-MSC reversed demyelination of the sciatic nerve produced by PSNL. These data suggest that AD- and UC-MSCs may help in the recovery of neuropathic pain via the different regulation; AD-MSCs exhibited their effects via suppressed neuronal damage and anti-inflammatory actions, while UC-MSCs exhibited their effects via suppressed neuronal damage, anti-inflammatory actions and remyelination.
Identifiants
pubmed: 35157707
doi: 10.1371/journal.pone.0262892
pii: PONE-D-20-40387
pmc: PMC8843230
doi:
Substances chimiques
Activating Transcription Factor 3
0
Aif1 protein, rat
0
Atf3 protein, rat
0
Calcium-Binding Proteins
0
Microfilament Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0262892Déclaration de conflit d'intérêts
Yasuhito Uezono and Kanako Miyano received grant support from Biomimetics Sympathies Inc. Minori Ikehata, Yasuhiro Nose, Seiichi Yoshihara and Katsuyuki Oki are employees of Biomimetics Sympathies Inc. The other authors declare no competing interests.
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