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Anti-Inflammatory Mechanism of Neural Stem Cell Transplantation in Spinal Cord Injury

Neural stem cell (NSC) transplantation has been proposed to promote functional recovery after spinal cord injury. However, a detailed understanding of the mechanisms of how NSCs exert their therapeutic plasticity is lacking. We transplanted mouse NSCs into the injured spinal cord seven days after SC...

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Autores principales: Cheng, Zhijian, Zhu, Wen, Cao, Kai, Wu, Fei, Li, Jin, Wang, Guoyu, Li, Haopen, Lu, Ming, Ren, Yi, He, Xijing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5037660/
https://www.ncbi.nlm.nih.gov/pubmed/27563878
http://dx.doi.org/10.3390/ijms17091380
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author Cheng, Zhijian
Zhu, Wen
Cao, Kai
Wu, Fei
Li, Jin
Wang, Guoyu
Li, Haopen
Lu, Ming
Ren, Yi
He, Xijing
author_facet Cheng, Zhijian
Zhu, Wen
Cao, Kai
Wu, Fei
Li, Jin
Wang, Guoyu
Li, Haopen
Lu, Ming
Ren, Yi
He, Xijing
author_sort Cheng, Zhijian
collection PubMed
description Neural stem cell (NSC) transplantation has been proposed to promote functional recovery after spinal cord injury. However, a detailed understanding of the mechanisms of how NSCs exert their therapeutic plasticity is lacking. We transplanted mouse NSCs into the injured spinal cord seven days after SCI, and the Basso Mouse Scale (BMS) score was performed to assess locomotor function. The anti-inflammatory effects of NSC transplantation was analyzed by immunofluorescence staining of neutrophil and macrophages and the detection of mRNA levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and interleukin-12 (IL-12). Furthermore, bone marrow-derived macrophages (BMDMs) were co-cultured with NSCs and followed by analyzing the mRNA levels of inducible nitric oxide synthase (iNOS), TNF-α, IL-1β, IL-6 and IL-10 with quantitative real-time PCR. The production of TNF-α and IL-1β by BMDMs was examined using the enzyme-linked immunosorbent assay (ELISA). Transplanted NSCs had significantly increased BMS scores (p < 0.05). Histological results showed that the grafted NSCs migrated from the injection site toward the injured area. NSCs transplantation significantly reduced the number of neutrophils and iNOS+/Mac-2+ cells at the epicenter of the injured area (p < 0.05). Meanwhile, mRNA levels of TNF-α, IL-1β, IL-6 and IL-12 in the NSCs transplantation group were significantly decreased compared to the control group. Furthermore, NSCs inhibited the iNOS expression of BMDMs and the release of inflammatory factors by macrophages in vitro (p < 0.05). These results suggest that NSC transplantation could modulate SCI-induced inflammatory responses and enhance neurological function after SCI via reducing M1 macrophage activation and infiltrating neutrophils. Thus, this study provides a new insight into the mechanisms responsible for the anti-inflammatory effect of NSC transplantation after SCI.
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spelling pubmed-50376602016-09-29 Anti-Inflammatory Mechanism of Neural Stem Cell Transplantation in Spinal Cord Injury Cheng, Zhijian Zhu, Wen Cao, Kai Wu, Fei Li, Jin Wang, Guoyu Li, Haopen Lu, Ming Ren, Yi He, Xijing Int J Mol Sci Article Neural stem cell (NSC) transplantation has been proposed to promote functional recovery after spinal cord injury. However, a detailed understanding of the mechanisms of how NSCs exert their therapeutic plasticity is lacking. We transplanted mouse NSCs into the injured spinal cord seven days after SCI, and the Basso Mouse Scale (BMS) score was performed to assess locomotor function. The anti-inflammatory effects of NSC transplantation was analyzed by immunofluorescence staining of neutrophil and macrophages and the detection of mRNA levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and interleukin-12 (IL-12). Furthermore, bone marrow-derived macrophages (BMDMs) were co-cultured with NSCs and followed by analyzing the mRNA levels of inducible nitric oxide synthase (iNOS), TNF-α, IL-1β, IL-6 and IL-10 with quantitative real-time PCR. The production of TNF-α and IL-1β by BMDMs was examined using the enzyme-linked immunosorbent assay (ELISA). Transplanted NSCs had significantly increased BMS scores (p < 0.05). Histological results showed that the grafted NSCs migrated from the injection site toward the injured area. NSCs transplantation significantly reduced the number of neutrophils and iNOS+/Mac-2+ cells at the epicenter of the injured area (p < 0.05). Meanwhile, mRNA levels of TNF-α, IL-1β, IL-6 and IL-12 in the NSCs transplantation group were significantly decreased compared to the control group. Furthermore, NSCs inhibited the iNOS expression of BMDMs and the release of inflammatory factors by macrophages in vitro (p < 0.05). These results suggest that NSC transplantation could modulate SCI-induced inflammatory responses and enhance neurological function after SCI via reducing M1 macrophage activation and infiltrating neutrophils. Thus, this study provides a new insight into the mechanisms responsible for the anti-inflammatory effect of NSC transplantation after SCI. MDPI 2016-08-23 /pmc/articles/PMC5037660/ /pubmed/27563878 http://dx.doi.org/10.3390/ijms17091380 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cheng, Zhijian
Zhu, Wen
Cao, Kai
Wu, Fei
Li, Jin
Wang, Guoyu
Li, Haopen
Lu, Ming
Ren, Yi
He, Xijing
Anti-Inflammatory Mechanism of Neural Stem Cell Transplantation in Spinal Cord Injury
title Anti-Inflammatory Mechanism of Neural Stem Cell Transplantation in Spinal Cord Injury
title_full Anti-Inflammatory Mechanism of Neural Stem Cell Transplantation in Spinal Cord Injury
title_fullStr Anti-Inflammatory Mechanism of Neural Stem Cell Transplantation in Spinal Cord Injury
title_full_unstemmed Anti-Inflammatory Mechanism of Neural Stem Cell Transplantation in Spinal Cord Injury
title_short Anti-Inflammatory Mechanism of Neural Stem Cell Transplantation in Spinal Cord Injury
title_sort anti-inflammatory mechanism of neural stem cell transplantation in spinal cord injury
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5037660/
https://www.ncbi.nlm.nih.gov/pubmed/27563878
http://dx.doi.org/10.3390/ijms17091380
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