Bone Marrow Mesenchymal Stem-Cell Transplantation Promotes Functional Improvement Associated with CNTF-STAT3 Activation after Hemi-Sectioned Spinal Cord Injury in Tree Shrews

Hemi-sectioned spinal cord injury (hSCI) can lead to spastic paralysis on the injured side, as well as flaccid paralysis on the contralateral side, which can negatively affect a patient’s daily life. Stem-cell therapy may offer an effective treatment option for individuals with hSCI. To examine the...

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Publicado no:Front Cell Neurosci
Main Authors: Xiong, Liu-Lin, Liu, Fei, Lu, Bing-Tuan, Zhao, Wen-Ling, Dong, Xiu-Juan, Liu, Jia, Zhang, Rong-Ping, Zhang, Piao, Wang, Ting-Hua
Formato: Artigo
Idioma:Inglês
Publicado em: Frontiers Media S.A. 2017
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Neuroscience
Acesso em linha:https://ncbi.nlm.nih.gov/pmc/articles/PMC5487382/
https://ncbi.nlm.nih.gov/pubmed/28701922
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.3389/fncel.2017.00172
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spelling pubmed-54873822017-07-12 Bone Marrow Mesenchymal Stem-Cell Transplantation Promotes Functional Improvement Associated with CNTF-STAT3 Activation after Hemi-Sectioned Spinal Cord Injury in Tree Shrews Xiong, Liu-Lin Liu, Fei Lu, Bing-Tuan Zhao, Wen-Ling Dong, Xiu-Juan Liu, Jia Zhang, Rong-Ping Zhang, Piao Wang, Ting-Hua Front Cell Neurosci Neuroscience Hemi-sectioned spinal cord injury (hSCI) can lead to spastic paralysis on the injured side, as well as flaccid paralysis on the contralateral side, which can negatively affect a patient’s daily life. Stem-cell therapy may offer an effective treatment option for individuals with hSCI. To examine the role of bone marrow mesenchymal stem cells (BMSCs) transplantation on hSCI and explore related mechanisms in the tree shrews, here, we created a model of hSCI by inducing injury at the tenth thoracic vertebra (T10). Hoechst 33342-labeled BMSCs derived from adult tree shrews were isolated, cultured, and implanted into the spinal cord around the injury site at 9 days after injury. The isolated BMSCs were able to survive, proliferate and release a variety of neurotrophic factors (NTFs) both in vitro and in vivo. At 28 days after injury, compared with the sham group, the hSCI group displayed scar formation and dramatic elevations in the mean interleukin 1 beta (IL-1β) density and cell apoptosis level, whereas the expression of signal transducer and activator of transcription 3 (STAT3) and ciliary neurotrophic factor (CNTF) mRNA was reduced. Following BMSC transplantation, motoneurons extent of shrinkage were reduced and the animals’ Basso, Beattie, and Bresnahan (BBB) locomotion scale scores were significantly higher at 21 and 28 days after injury when compared with the injured group. Moreover, the hSCI-induced elevations in scar formation, IL-1β, and cell apoptosis were reduced by BMSC transplantation to levels that were close to those of the sham group. Corresponding elevations in the expression of STAT3 and CNTF mRNA were observed in the hSCI + BMSCs group, and the levels were not significantly different from those observed in the sham group. Together, our results support that grafted BMSCs can significantly improve locomotor function in tree shrews subjected to hSCI and that this improvement is associated with the upregulation of CNTF and STAT3 signaling. Frontiers Media S.A. 2017-06-28 /pmc/articles/PMC5487382/ /pubmed/28701922 http://dx.doi.org/10.3389/fncel.2017.00172 Text en Copyright © 2017 Xiong, Liu, Lu, Zhao, Dong, Liu, Zhang, Zhang and Wang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
institution US NLM
collection PubMed Central
language Inglês
format Artigo
topic Neuroscience
spellingShingle Neuroscience
Xiong, Liu-Lin
Liu, Fei
Lu, Bing-Tuan
Zhao, Wen-Ling
Dong, Xiu-Juan
Liu, Jia
Zhang, Rong-Ping
Zhang, Piao
Wang, Ting-Hua
Bone Marrow Mesenchymal Stem-Cell Transplantation Promotes Functional Improvement Associated with CNTF-STAT3 Activation after Hemi-Sectioned Spinal Cord Injury in Tree Shrews
description Hemi-sectioned spinal cord injury (hSCI) can lead to spastic paralysis on the injured side, as well as flaccid paralysis on the contralateral side, which can negatively affect a patient’s daily life. Stem-cell therapy may offer an effective treatment option for individuals with hSCI. To examine the role of bone marrow mesenchymal stem cells (BMSCs) transplantation on hSCI and explore related mechanisms in the tree shrews, here, we created a model of hSCI by inducing injury at the tenth thoracic vertebra (T10). Hoechst 33342-labeled BMSCs derived from adult tree shrews were isolated, cultured, and implanted into the spinal cord around the injury site at 9 days after injury. The isolated BMSCs were able to survive, proliferate and release a variety of neurotrophic factors (NTFs) both in vitro and in vivo. At 28 days after injury, compared with the sham group, the hSCI group displayed scar formation and dramatic elevations in the mean interleukin 1 beta (IL-1β) density and cell apoptosis level, whereas the expression of signal transducer and activator of transcription 3 (STAT3) and ciliary neurotrophic factor (CNTF) mRNA was reduced. Following BMSC transplantation, motoneurons extent of shrinkage were reduced and the animals’ Basso, Beattie, and Bresnahan (BBB) locomotion scale scores were significantly higher at 21 and 28 days after injury when compared with the injured group. Moreover, the hSCI-induced elevations in scar formation, IL-1β, and cell apoptosis were reduced by BMSC transplantation to levels that were close to those of the sham group. Corresponding elevations in the expression of STAT3 and CNTF mRNA were observed in the hSCI + BMSCs group, and the levels were not significantly different from those observed in the sham group. Together, our results support that grafted BMSCs can significantly improve locomotor function in tree shrews subjected to hSCI and that this improvement is associated with the upregulation of CNTF and STAT3 signaling.
author Xiong, Liu-Lin
Liu, Fei
Lu, Bing-Tuan
Zhao, Wen-Ling
Dong, Xiu-Juan
Liu, Jia
Zhang, Rong-Ping
Zhang, Piao
Wang, Ting-Hua
author_facet Xiong, Liu-Lin
Liu, Fei
Lu, Bing-Tuan
Zhao, Wen-Ling
Dong, Xiu-Juan
Liu, Jia
Zhang, Rong-Ping
Zhang, Piao
Wang, Ting-Hua
author_sort Xiong, Liu-Lin
title Bone Marrow Mesenchymal Stem-Cell Transplantation Promotes Functional Improvement Associated with CNTF-STAT3 Activation after Hemi-Sectioned Spinal Cord Injury in Tree Shrews
title_short Bone Marrow Mesenchymal Stem-Cell Transplantation Promotes Functional Improvement Associated with CNTF-STAT3 Activation after Hemi-Sectioned Spinal Cord Injury in Tree Shrews
title_full Bone Marrow Mesenchymal Stem-Cell Transplantation Promotes Functional Improvement Associated with CNTF-STAT3 Activation after Hemi-Sectioned Spinal Cord Injury in Tree Shrews
title_fullStr Bone Marrow Mesenchymal Stem-Cell Transplantation Promotes Functional Improvement Associated with CNTF-STAT3 Activation after Hemi-Sectioned Spinal Cord Injury in Tree Shrews
title_full_unstemmed Bone Marrow Mesenchymal Stem-Cell Transplantation Promotes Functional Improvement Associated with CNTF-STAT3 Activation after Hemi-Sectioned Spinal Cord Injury in Tree Shrews
title_sort bone marrow mesenchymal stem-cell transplantation promotes functional improvement associated with cntf-stat3 activation after hemi-sectioned spinal cord injury in tree shrews
publisher Frontiers Media S.A.
container_title Front Cell Neurosci
publishDate 2017
url https://ncbi.nlm.nih.gov/pmc/articles/PMC5487382/
https://ncbi.nlm.nih.gov/pubmed/28701922
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.3389/fncel.2017.00172
_version_ 1819494203642609664

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