Transdifferentiation-Induced Neural Stem Cells Promote Recovery of Middle Cerebral Artery Stroke Rats.

Induced neural stem cells (iNSCs) can be directly transdifferentiated from somatic cells. One potential clinical application of the iNSCs is for nerve regeneration. However, it is unknown whether iNSCs function in disease models. We produced transdifferentiated iNSCs by conditional overexpressing Oc...

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Main Authors: Hui Yao, Mou Gao, Jianhua Ma, Maoying Zhang, Shaowu Li, Bingshan Wu, Xiaohu Nie, Jiao Jiao, Hao Zhao, Shanshan Wang, Yuanyuan Yang, Yesen Zhang, Yilin Sun, Max S Wicha, Alfred E Chang, Shaorong Gao, Qiao Li, Ruxiang Xu
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4564190?pdf=render
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author Hui Yao
Mou Gao
Jianhua Ma
Maoying Zhang
Shaowu Li
Bingshan Wu
Xiaohu Nie
Jiao Jiao
Hao Zhao
Shanshan Wang
Yuanyuan Yang
Yesen Zhang
Yilin Sun
Max S Wicha
Alfred E Chang
Shaorong Gao
Qiao Li
Ruxiang Xu
author_facet Hui Yao
Mou Gao
Jianhua Ma
Maoying Zhang
Shaowu Li
Bingshan Wu
Xiaohu Nie
Jiao Jiao
Hao Zhao
Shanshan Wang
Yuanyuan Yang
Yesen Zhang
Yilin Sun
Max S Wicha
Alfred E Chang
Shaorong Gao
Qiao Li
Ruxiang Xu
author_sort Hui Yao
collection DOAJ
description Induced neural stem cells (iNSCs) can be directly transdifferentiated from somatic cells. One potential clinical application of the iNSCs is for nerve regeneration. However, it is unknown whether iNSCs function in disease models. We produced transdifferentiated iNSCs by conditional overexpressing Oct4, Sox2, Klf4, c-Mycin mouse embryonic fibroblasts. They expanded readily in vitro and expressed NSC mRNA profile and protein markers. These iNSCs differentiated into mature astrocytes, neurons and oligodendrocytes in vitro. Importantly, they reduced lesion size, promoted the recovery of motor and sensory function as well as metabolism status in middle cerebral artery stroke rats. These iNSCs secreted nerve growth factors, which was associated with observed protection of neurons from apoptosis. Furthermore, iNSCs migrated to and passed through the lesion in the cerebral cortex, where Tuj1+ neurons were detected. These findings have revealed the function of transdifferentiated iNSCs in vivo, and thus provide experimental evidence to support the development of personalized regenerative therapy for CNS diseases by using genetically engineered autologous somatic cells.
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spelling doaj.art-ba740262df264627be6746d0c0a74bfd2022-12-21T19:26:01ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01109e013721110.1371/journal.pone.0137211Transdifferentiation-Induced Neural Stem Cells Promote Recovery of Middle Cerebral Artery Stroke Rats.Hui YaoMou GaoJianhua MaMaoying ZhangShaowu LiBingshan WuXiaohu NieJiao JiaoHao ZhaoShanshan WangYuanyuan YangYesen ZhangYilin SunMax S WichaAlfred E ChangShaorong GaoQiao LiRuxiang XuInduced neural stem cells (iNSCs) can be directly transdifferentiated from somatic cells. One potential clinical application of the iNSCs is for nerve regeneration. However, it is unknown whether iNSCs function in disease models. We produced transdifferentiated iNSCs by conditional overexpressing Oct4, Sox2, Klf4, c-Mycin mouse embryonic fibroblasts. They expanded readily in vitro and expressed NSC mRNA profile and protein markers. These iNSCs differentiated into mature astrocytes, neurons and oligodendrocytes in vitro. Importantly, they reduced lesion size, promoted the recovery of motor and sensory function as well as metabolism status in middle cerebral artery stroke rats. These iNSCs secreted nerve growth factors, which was associated with observed protection of neurons from apoptosis. Furthermore, iNSCs migrated to and passed through the lesion in the cerebral cortex, where Tuj1+ neurons were detected. These findings have revealed the function of transdifferentiated iNSCs in vivo, and thus provide experimental evidence to support the development of personalized regenerative therapy for CNS diseases by using genetically engineered autologous somatic cells.http://europepmc.org/articles/PMC4564190?pdf=render
spellingShingle Hui Yao
Mou Gao
Jianhua Ma
Maoying Zhang
Shaowu Li
Bingshan Wu
Xiaohu Nie
Jiao Jiao
Hao Zhao
Shanshan Wang
Yuanyuan Yang
Yesen Zhang
Yilin Sun
Max S Wicha
Alfred E Chang
Shaorong Gao
Qiao Li
Ruxiang Xu
Transdifferentiation-Induced Neural Stem Cells Promote Recovery of Middle Cerebral Artery Stroke Rats.
PLoS ONE
title Transdifferentiation-Induced Neural Stem Cells Promote Recovery of Middle Cerebral Artery Stroke Rats.
title_full Transdifferentiation-Induced Neural Stem Cells Promote Recovery of Middle Cerebral Artery Stroke Rats.
title_fullStr Transdifferentiation-Induced Neural Stem Cells Promote Recovery of Middle Cerebral Artery Stroke Rats.
title_full_unstemmed Transdifferentiation-Induced Neural Stem Cells Promote Recovery of Middle Cerebral Artery Stroke Rats.
title_short Transdifferentiation-Induced Neural Stem Cells Promote Recovery of Middle Cerebral Artery Stroke Rats.
title_sort transdifferentiation induced neural stem cells promote recovery of middle cerebral artery stroke rats
url http://europepmc.org/articles/PMC4564190?pdf=render
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