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Intravenous multipotent adult progenitor cell treatment decreases inflammation leading to functional recovery following spinal cord injury

Following spinal cord injury (SCI), immune-mediated secondary processes exacerbate the extent of permanent neurological deficits. We investigated the capacity of adult bone marrow-derived stem cells, which exhibit immunomodulatory properties, to alter inflammation and promote recovery following SCI....

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Autores principales: DePaul, Marc A., Palmer, Marc, Lang, Bradley T., Cutrone, Rochelle, Tran, Amanda P., Madalena, Kathryn M., Bogaerts, Annelies, Hamilton, Jason A., Deans, Robert J., Mays, Robert W., Busch, Sarah A., Silver, Jerry
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4652166/
https://www.ncbi.nlm.nih.gov/pubmed/26582249
http://dx.doi.org/10.1038/srep16795
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author DePaul, Marc A.
Palmer, Marc
Lang, Bradley T.
Cutrone, Rochelle
Tran, Amanda P.
Madalena, Kathryn M.
Bogaerts, Annelies
Hamilton, Jason A.
Deans, Robert J.
Mays, Robert W.
Busch, Sarah A.
Silver, Jerry
author_facet DePaul, Marc A.
Palmer, Marc
Lang, Bradley T.
Cutrone, Rochelle
Tran, Amanda P.
Madalena, Kathryn M.
Bogaerts, Annelies
Hamilton, Jason A.
Deans, Robert J.
Mays, Robert W.
Busch, Sarah A.
Silver, Jerry
author_sort DePaul, Marc A.
collection PubMed
description Following spinal cord injury (SCI), immune-mediated secondary processes exacerbate the extent of permanent neurological deficits. We investigated the capacity of adult bone marrow-derived stem cells, which exhibit immunomodulatory properties, to alter inflammation and promote recovery following SCI. In vitro, we show that human multipotent adult progenitor cells (MAPCs) have the ability to modulate macrophage activation, and prior exposure to MAPC secreted factors can reduce macrophage-mediated axonal dieback of dystrophic axons. Using a contusion model of SCI, we found that intravenous delivery of MAPCs one day, but not immediately, after SCI significantly improves urinary and locomotor recovery, which was associated with marked spinal cord tissue sparing. Intravenous MAPCs altered the immune response in the spinal cord and periphery, however biodistribution studies revealed that no MAPCs were found in the cord and instead preferentially homed to the spleen. Our results demonstrate that MAPCs exert their primary effects in the periphery and provide strong support for the use of these cells in acute human contusive SCI.
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spelling pubmed-46521662015-11-24 Intravenous multipotent adult progenitor cell treatment decreases inflammation leading to functional recovery following spinal cord injury DePaul, Marc A. Palmer, Marc Lang, Bradley T. Cutrone, Rochelle Tran, Amanda P. Madalena, Kathryn M. Bogaerts, Annelies Hamilton, Jason A. Deans, Robert J. Mays, Robert W. Busch, Sarah A. Silver, Jerry Sci Rep Article Following spinal cord injury (SCI), immune-mediated secondary processes exacerbate the extent of permanent neurological deficits. We investigated the capacity of adult bone marrow-derived stem cells, which exhibit immunomodulatory properties, to alter inflammation and promote recovery following SCI. In vitro, we show that human multipotent adult progenitor cells (MAPCs) have the ability to modulate macrophage activation, and prior exposure to MAPC secreted factors can reduce macrophage-mediated axonal dieback of dystrophic axons. Using a contusion model of SCI, we found that intravenous delivery of MAPCs one day, but not immediately, after SCI significantly improves urinary and locomotor recovery, which was associated with marked spinal cord tissue sparing. Intravenous MAPCs altered the immune response in the spinal cord and periphery, however biodistribution studies revealed that no MAPCs were found in the cord and instead preferentially homed to the spleen. Our results demonstrate that MAPCs exert their primary effects in the periphery and provide strong support for the use of these cells in acute human contusive SCI. Nature Publishing Group 2015-11-19 /pmc/articles/PMC4652166/ /pubmed/26582249 http://dx.doi.org/10.1038/srep16795 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
DePaul, Marc A.
Palmer, Marc
Lang, Bradley T.
Cutrone, Rochelle
Tran, Amanda P.
Madalena, Kathryn M.
Bogaerts, Annelies
Hamilton, Jason A.
Deans, Robert J.
Mays, Robert W.
Busch, Sarah A.
Silver, Jerry
Intravenous multipotent adult progenitor cell treatment decreases inflammation leading to functional recovery following spinal cord injury
title Intravenous multipotent adult progenitor cell treatment decreases inflammation leading to functional recovery following spinal cord injury
title_full Intravenous multipotent adult progenitor cell treatment decreases inflammation leading to functional recovery following spinal cord injury
title_fullStr Intravenous multipotent adult progenitor cell treatment decreases inflammation leading to functional recovery following spinal cord injury
title_full_unstemmed Intravenous multipotent adult progenitor cell treatment decreases inflammation leading to functional recovery following spinal cord injury
title_short Intravenous multipotent adult progenitor cell treatment decreases inflammation leading to functional recovery following spinal cord injury
title_sort intravenous multipotent adult progenitor cell treatment decreases inflammation leading to functional recovery following spinal cord injury
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4652166/
https://www.ncbi.nlm.nih.gov/pubmed/26582249
http://dx.doi.org/10.1038/srep16795
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