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Human Neural Precursor Cells Promote Neurologic Recovery in a Viral Model of Multiple Sclerosis
Using a viral model of the demyelinating disease multiple sclerosis (MS), we show that intraspinal transplantation of human embryonic stem cell-derived neural precursor cells (hNPCs) results in sustained clinical recovery, although hNPCs were not detectable beyond day 8 posttransplantation. Improved...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4050357/ https://www.ncbi.nlm.nih.gov/pubmed/24936469 http://dx.doi.org/10.1016/j.stemcr.2014.04.005 |
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author | Chen, Lu Coleman, Ronald Leang, Ronika Tran, Ha Kopf, Alexandra Walsh, Craig M. Sears-Kraxberger, Ilse Steward, Oswald Macklin, Wendy B. Loring, Jeanne F. Lane, Thomas E. |
author_facet | Chen, Lu Coleman, Ronald Leang, Ronika Tran, Ha Kopf, Alexandra Walsh, Craig M. Sears-Kraxberger, Ilse Steward, Oswald Macklin, Wendy B. Loring, Jeanne F. Lane, Thomas E. |
author_sort | Chen, Lu |
collection | PubMed |
description | Using a viral model of the demyelinating disease multiple sclerosis (MS), we show that intraspinal transplantation of human embryonic stem cell-derived neural precursor cells (hNPCs) results in sustained clinical recovery, although hNPCs were not detectable beyond day 8 posttransplantation. Improved motor skills were associated with a reduction in neuroinflammation, decreased demyelination, and enhanced remyelination. Evidence indicates that the reduced neuroinflammation is correlated with an increased number of CD4(+)CD25(+)FOXP3(+) regulatory T cells (Tregs) within the spinal cords. Coculture of hNPCs with activated T cells resulted in reduced T cell proliferation and increased Treg numbers. The hNPCs acted, in part, through secretion of TGF-β1 and TGF-β2. These findings indicate that the transient presence of hNPCs transplanted in an animal model of MS has powerful immunomodulatory effects and mediates recovery. Further investigation of the restorative effects of hNPC transplantation may aid in the development of clinically relevant MS treatments. |
format | Online Article Text |
id | pubmed-4050357 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-40503572014-06-16 Human Neural Precursor Cells Promote Neurologic Recovery in a Viral Model of Multiple Sclerosis Chen, Lu Coleman, Ronald Leang, Ronika Tran, Ha Kopf, Alexandra Walsh, Craig M. Sears-Kraxberger, Ilse Steward, Oswald Macklin, Wendy B. Loring, Jeanne F. Lane, Thomas E. Stem Cell Reports Article Using a viral model of the demyelinating disease multiple sclerosis (MS), we show that intraspinal transplantation of human embryonic stem cell-derived neural precursor cells (hNPCs) results in sustained clinical recovery, although hNPCs were not detectable beyond day 8 posttransplantation. Improved motor skills were associated with a reduction in neuroinflammation, decreased demyelination, and enhanced remyelination. Evidence indicates that the reduced neuroinflammation is correlated with an increased number of CD4(+)CD25(+)FOXP3(+) regulatory T cells (Tregs) within the spinal cords. Coculture of hNPCs with activated T cells resulted in reduced T cell proliferation and increased Treg numbers. The hNPCs acted, in part, through secretion of TGF-β1 and TGF-β2. These findings indicate that the transient presence of hNPCs transplanted in an animal model of MS has powerful immunomodulatory effects and mediates recovery. Further investigation of the restorative effects of hNPC transplantation may aid in the development of clinically relevant MS treatments. Elsevier 2014-05-15 /pmc/articles/PMC4050357/ /pubmed/24936469 http://dx.doi.org/10.1016/j.stemcr.2014.04.005 Text en © 2014 The Authors http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/). |
spellingShingle | Article Chen, Lu Coleman, Ronald Leang, Ronika Tran, Ha Kopf, Alexandra Walsh, Craig M. Sears-Kraxberger, Ilse Steward, Oswald Macklin, Wendy B. Loring, Jeanne F. Lane, Thomas E. Human Neural Precursor Cells Promote Neurologic Recovery in a Viral Model of Multiple Sclerosis |
title | Human Neural Precursor Cells Promote Neurologic Recovery in a Viral Model of Multiple Sclerosis |
title_full | Human Neural Precursor Cells Promote Neurologic Recovery in a Viral Model of Multiple Sclerosis |
title_fullStr | Human Neural Precursor Cells Promote Neurologic Recovery in a Viral Model of Multiple Sclerosis |
title_full_unstemmed | Human Neural Precursor Cells Promote Neurologic Recovery in a Viral Model of Multiple Sclerosis |
title_short | Human Neural Precursor Cells Promote Neurologic Recovery in a Viral Model of Multiple Sclerosis |
title_sort | human neural precursor cells promote neurologic recovery in a viral model of multiple sclerosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4050357/ https://www.ncbi.nlm.nih.gov/pubmed/24936469 http://dx.doi.org/10.1016/j.stemcr.2014.04.005 |
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