Novel Therapeutic Transplantation of Induced Neural Stem Cells for Stroke

Somatic cells can be directly converted into induced neural stem cells (iNSCs) by defined transcription factors. However, the therapeutic effect of undifferentiated iNSCs on ischemic stroke has not been demonstrated. In this study, we used a mouse model of transient middle cerebral artery occlusion...

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Main Authors: Toru Yamashita, Wentao Liu, Yoshiaki Matsumura, Ryosuke Miyagi, Yun Zhai, Momoko Kusaki, Nozomi Hishikawa, Yasuyuki Ohta, Sung Min Kim, Tae Hwan Kwak, Dong Wook Han, Koji Abe M.D., Ph.D.
Format: Article
Language:English
Published: SAGE Publishing 2017-03-01
Series:Cell Transplantation
Online Access:https://doi.org/10.3727/096368916X692988
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spelling doaj-9cdccb674eb84c699c3bf0c6b2f9e9552020-11-25T03:28:47ZengSAGE PublishingCell Transplantation0963-68971555-38922017-03-012610.3727/096368916X692988Novel Therapeutic Transplantation of Induced Neural Stem Cells for StrokeToru Yamashita0Wentao Liu1Yoshiaki Matsumura2Ryosuke Miyagi3Yun Zhai4Momoko Kusaki5Nozomi Hishikawa6Yasuyuki Ohta7Sung Min Kim8Tae Hwan Kwak9Dong Wook Han10Koji Abe M.D., Ph.D.11Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, JapanDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, JapanDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, JapanDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, JapanDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, JapanDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, JapanDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, JapanDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, JapanDepartment of Stem Cell Biology, School of Medicine, Konkuk University, Seoul, South KoreaDepartment of Stem Cell Biology, School of Medicine, Konkuk University, Seoul, South KoreaDepartment of Advanced Translational Medicine, KU Open-Innovation Center, School of Medicine, Konkuk University, Seoul, South KoreaDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, JapanSomatic cells can be directly converted into induced neural stem cells (iNSCs) by defined transcription factors. However, the therapeutic effect of undifferentiated iNSCs on ischemic stroke has not been demonstrated. In this study, we used a mouse model of transient middle cerebral artery occlusion (tMCAO). iNSCs (5 × 10 5 ) were injected directly into the ipsilateral striatum and cortex 24 h after tMCAO. Histological analysis was performed at 7 days, 28 days, and 8 months after tMCAO. We found that iNSC transplantation successfully improved the survival rate of stroke model mice with significant functional recovery from the stroke. The fate of engrafted iNSCs was that the majority of iNSCs had differentiated into astroglial cells but not into neural cells in both the sham-operated brain and the poststroke brain without forming a tumor up to 8 months after tMCAO. Our data suggest that the directly converted iNSCs can be regarded as a candidate of safe cell resource for transplantation therapy in patients suffering from ischemic stroke.https://doi.org/10.3727/096368916X692988
collection DOAJ
language English
format Article
sources DOAJ
author Toru Yamashita
Wentao Liu
Yoshiaki Matsumura
Ryosuke Miyagi
Yun Zhai
Momoko Kusaki
Nozomi Hishikawa
Yasuyuki Ohta
Sung Min Kim
Tae Hwan Kwak
Dong Wook Han
Koji Abe M.D., Ph.D.
spellingShingle Toru Yamashita
Wentao Liu
Yoshiaki Matsumura
Ryosuke Miyagi
Yun Zhai
Momoko Kusaki
Nozomi Hishikawa
Yasuyuki Ohta
Sung Min Kim
Tae Hwan Kwak
Dong Wook Han
Koji Abe M.D., Ph.D.
Novel Therapeutic Transplantation of Induced Neural Stem Cells for Stroke
Cell Transplantation
author_facet Toru Yamashita
Wentao Liu
Yoshiaki Matsumura
Ryosuke Miyagi
Yun Zhai
Momoko Kusaki
Nozomi Hishikawa
Yasuyuki Ohta
Sung Min Kim
Tae Hwan Kwak
Dong Wook Han
Koji Abe M.D., Ph.D.
author_sort Toru Yamashita
title Novel Therapeutic Transplantation of Induced Neural Stem Cells for Stroke
title_short Novel Therapeutic Transplantation of Induced Neural Stem Cells for Stroke
title_full Novel Therapeutic Transplantation of Induced Neural Stem Cells for Stroke
title_fullStr Novel Therapeutic Transplantation of Induced Neural Stem Cells for Stroke
title_full_unstemmed Novel Therapeutic Transplantation of Induced Neural Stem Cells for Stroke
title_sort novel therapeutic transplantation of induced neural stem cells for stroke
publisher SAGE Publishing
series Cell Transplantation
issn 0963-6897
1555-3892
publishDate 2017-03-01
description Somatic cells can be directly converted into induced neural stem cells (iNSCs) by defined transcription factors. However, the therapeutic effect of undifferentiated iNSCs on ischemic stroke has not been demonstrated. In this study, we used a mouse model of transient middle cerebral artery occlusion (tMCAO). iNSCs (5 × 10 5 ) were injected directly into the ipsilateral striatum and cortex 24 h after tMCAO. Histological analysis was performed at 7 days, 28 days, and 8 months after tMCAO. We found that iNSC transplantation successfully improved the survival rate of stroke model mice with significant functional recovery from the stroke. The fate of engrafted iNSCs was that the majority of iNSCs had differentiated into astroglial cells but not into neural cells in both the sham-operated brain and the poststroke brain without forming a tumor up to 8 months after tMCAO. Our data suggest that the directly converted iNSCs can be regarded as a candidate of safe cell resource for transplantation therapy in patients suffering from ischemic stroke.
url https://doi.org/10.3727/096368916X692988
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