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Engrafted Neural Stem/Progenitor Cells Promote Functional Recovery through Synapse Reorganization with Spared Host Neurons after Spinal Cord Injury
Neural stem/progenitor cell (NSPC) transplantation is a promising therapeutic strategy for spinal cord injury (SCI). However, the efficacy of NSPC transplantation on severe SCI is poorly understood. We herein show that NSPC transplantation promotes functional recovery after mild and moderate SCI, bu...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4618657/ https://www.ncbi.nlm.nih.gov/pubmed/26190527 http://dx.doi.org/10.1016/j.stemcr.2015.06.004 |
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author | Yokota, Kazuya Kobayakawa, Kazu Kubota, Kensuke Miyawaki, Atsushi Okano, Hideyuki Ohkawa, Yasuyuki Iwamoto, Yukihide Okada, Seiji |
author_facet | Yokota, Kazuya Kobayakawa, Kazu Kubota, Kensuke Miyawaki, Atsushi Okano, Hideyuki Ohkawa, Yasuyuki Iwamoto, Yukihide Okada, Seiji |
author_sort | Yokota, Kazuya |
collection | PubMed |
description | Neural stem/progenitor cell (NSPC) transplantation is a promising therapeutic strategy for spinal cord injury (SCI). However, the efficacy of NSPC transplantation on severe SCI is poorly understood. We herein show that NSPC transplantation promotes functional recovery after mild and moderate SCI, but not after severe SCI. In severe SCI mice, there were few remaining host neurons within the range of NSPC engraftment; thus, we examined whether the co-distribution of transplant and host is a contributory factor for functional improvement. A cellular selective analysis using laser microdissection revealed that drug-induced host neuronal ablation considerably decreased the synaptogenic potential of the engrafted NSPCs. Furthermore, following host neuronal ablation, neuronal retrograde tracing showed less propriospinal relay connections bridging the lesion after NSPC transplantation. Our findings suggest that the interactive synaptic reorganization between engrafted NSPCs and spared host neurons is crucial for functional recovery, providing significant insight for establishing therapeutic strategies for severe SCI. |
format | Online Article Text |
id | pubmed-4618657 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-46186572015-11-24 Engrafted Neural Stem/Progenitor Cells Promote Functional Recovery through Synapse Reorganization with Spared Host Neurons after Spinal Cord Injury Yokota, Kazuya Kobayakawa, Kazu Kubota, Kensuke Miyawaki, Atsushi Okano, Hideyuki Ohkawa, Yasuyuki Iwamoto, Yukihide Okada, Seiji Stem Cell Reports Article Neural stem/progenitor cell (NSPC) transplantation is a promising therapeutic strategy for spinal cord injury (SCI). However, the efficacy of NSPC transplantation on severe SCI is poorly understood. We herein show that NSPC transplantation promotes functional recovery after mild and moderate SCI, but not after severe SCI. In severe SCI mice, there were few remaining host neurons within the range of NSPC engraftment; thus, we examined whether the co-distribution of transplant and host is a contributory factor for functional improvement. A cellular selective analysis using laser microdissection revealed that drug-induced host neuronal ablation considerably decreased the synaptogenic potential of the engrafted NSPCs. Furthermore, following host neuronal ablation, neuronal retrograde tracing showed less propriospinal relay connections bridging the lesion after NSPC transplantation. Our findings suggest that the interactive synaptic reorganization between engrafted NSPCs and spared host neurons is crucial for functional recovery, providing significant insight for establishing therapeutic strategies for severe SCI. Elsevier 2015-07-16 /pmc/articles/PMC4618657/ /pubmed/26190527 http://dx.doi.org/10.1016/j.stemcr.2015.06.004 Text en © 2015 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Yokota, Kazuya Kobayakawa, Kazu Kubota, Kensuke Miyawaki, Atsushi Okano, Hideyuki Ohkawa, Yasuyuki Iwamoto, Yukihide Okada, Seiji Engrafted Neural Stem/Progenitor Cells Promote Functional Recovery through Synapse Reorganization with Spared Host Neurons after Spinal Cord Injury |
title | Engrafted Neural Stem/Progenitor Cells Promote Functional Recovery through Synapse Reorganization with Spared Host Neurons after Spinal Cord Injury |
title_full | Engrafted Neural Stem/Progenitor Cells Promote Functional Recovery through Synapse Reorganization with Spared Host Neurons after Spinal Cord Injury |
title_fullStr | Engrafted Neural Stem/Progenitor Cells Promote Functional Recovery through Synapse Reorganization with Spared Host Neurons after Spinal Cord Injury |
title_full_unstemmed | Engrafted Neural Stem/Progenitor Cells Promote Functional Recovery through Synapse Reorganization with Spared Host Neurons after Spinal Cord Injury |
title_short | Engrafted Neural Stem/Progenitor Cells Promote Functional Recovery through Synapse Reorganization with Spared Host Neurons after Spinal Cord Injury |
title_sort | engrafted neural stem/progenitor cells promote functional recovery through synapse reorganization with spared host neurons after spinal cord injury |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4618657/ https://www.ncbi.nlm.nih.gov/pubmed/26190527 http://dx.doi.org/10.1016/j.stemcr.2015.06.004 |
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