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Human Embryonic Stem Cell-Derived Progenitors Assist Functional Sensory Axon Regeneration after Dorsal Root Avulsion Injury
Dorsal root avulsion results in permanent impairment of sensory functions due to disconnection between the peripheral and central nervous system. Improved strategies are therefore needed to reconnect injured sensory neurons with their spinal cord targets in order to achieve functional repair after b...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4459081/ https://www.ncbi.nlm.nih.gov/pubmed/26053681 http://dx.doi.org/10.1038/srep10666 |
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author | Hoeber, Jan Trolle, Carl Konig, Niclas Du, Zhongwei Gallo, Alessandro Hermans, Emmanuel Aldskogius, Hakan Shortland, Peter Zhang, Su-Chun Deumens, Ronald Kozlova, Elena N. |
author_facet | Hoeber, Jan Trolle, Carl Konig, Niclas Du, Zhongwei Gallo, Alessandro Hermans, Emmanuel Aldskogius, Hakan Shortland, Peter Zhang, Su-Chun Deumens, Ronald Kozlova, Elena N. |
author_sort | Hoeber, Jan |
collection | PubMed |
description | Dorsal root avulsion results in permanent impairment of sensory functions due to disconnection between the peripheral and central nervous system. Improved strategies are therefore needed to reconnect injured sensory neurons with their spinal cord targets in order to achieve functional repair after brachial and lumbosacral plexus avulsion injuries. Here, we show that sensory functions can be restored in the adult mouse if avulsed sensory fibers are bridged with the spinal cord by human neural progenitor (hNP) transplants. Responses to peripheral mechanical sensory stimulation were significantly improved in transplanted animals. Transganglionic tracing showed host sensory axons only in the spinal cord dorsal horn of treated animals. Immunohistochemical analysis confirmed that sensory fibers had grown through the bridge and showed robust survival and differentiation of the transplants. Section of the repaired dorsal roots distal to the transplant completely abolished the behavioral improvement. This demonstrates that hNP transplants promote recovery of sensorimotor functions after dorsal root avulsion, and that these effects are mediated by spinal ingrowth of host sensory axons. These results provide a rationale for the development of novel stem cell-based strategies for functionally useful bridging of the peripheral and central nervous system. |
format | Online Article Text |
id | pubmed-4459081 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-44590812015-06-17 Human Embryonic Stem Cell-Derived Progenitors Assist Functional Sensory Axon Regeneration after Dorsal Root Avulsion Injury Hoeber, Jan Trolle, Carl Konig, Niclas Du, Zhongwei Gallo, Alessandro Hermans, Emmanuel Aldskogius, Hakan Shortland, Peter Zhang, Su-Chun Deumens, Ronald Kozlova, Elena N. Sci Rep Article Dorsal root avulsion results in permanent impairment of sensory functions due to disconnection between the peripheral and central nervous system. Improved strategies are therefore needed to reconnect injured sensory neurons with their spinal cord targets in order to achieve functional repair after brachial and lumbosacral plexus avulsion injuries. Here, we show that sensory functions can be restored in the adult mouse if avulsed sensory fibers are bridged with the spinal cord by human neural progenitor (hNP) transplants. Responses to peripheral mechanical sensory stimulation were significantly improved in transplanted animals. Transganglionic tracing showed host sensory axons only in the spinal cord dorsal horn of treated animals. Immunohistochemical analysis confirmed that sensory fibers had grown through the bridge and showed robust survival and differentiation of the transplants. Section of the repaired dorsal roots distal to the transplant completely abolished the behavioral improvement. This demonstrates that hNP transplants promote recovery of sensorimotor functions after dorsal root avulsion, and that these effects are mediated by spinal ingrowth of host sensory axons. These results provide a rationale for the development of novel stem cell-based strategies for functionally useful bridging of the peripheral and central nervous system. Nature Publishing Group 2015-06-08 /pmc/articles/PMC4459081/ /pubmed/26053681 http://dx.doi.org/10.1038/srep10666 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Hoeber, Jan Trolle, Carl Konig, Niclas Du, Zhongwei Gallo, Alessandro Hermans, Emmanuel Aldskogius, Hakan Shortland, Peter Zhang, Su-Chun Deumens, Ronald Kozlova, Elena N. Human Embryonic Stem Cell-Derived Progenitors Assist Functional Sensory Axon Regeneration after Dorsal Root Avulsion Injury |
title | Human Embryonic Stem Cell-Derived Progenitors Assist Functional Sensory Axon Regeneration after Dorsal Root Avulsion Injury |
title_full | Human Embryonic Stem Cell-Derived Progenitors Assist Functional Sensory Axon Regeneration after Dorsal Root Avulsion Injury |
title_fullStr | Human Embryonic Stem Cell-Derived Progenitors Assist Functional Sensory Axon Regeneration after Dorsal Root Avulsion Injury |
title_full_unstemmed | Human Embryonic Stem Cell-Derived Progenitors Assist Functional Sensory Axon Regeneration after Dorsal Root Avulsion Injury |
title_short | Human Embryonic Stem Cell-Derived Progenitors Assist Functional Sensory Axon Regeneration after Dorsal Root Avulsion Injury |
title_sort | human embryonic stem cell-derived progenitors assist functional sensory axon regeneration after dorsal root avulsion injury |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4459081/ https://www.ncbi.nlm.nih.gov/pubmed/26053681 http://dx.doi.org/10.1038/srep10666 |
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