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Intravenous multipotent adult progenitor cell therapy after traumatic brain injury: modulation of the resident microglia population
INTRODUCTION: We have demonstrated previously that the intravenous delivery of multipotent adult progenitor cells (MAPC) after traumatic brain injury affords neuroprotection via interaction with splenocytes, leading to an increase in systemic anti-inflammatory cytokines. We hypothesize that the obse...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3546881/ https://www.ncbi.nlm.nih.gov/pubmed/23020860 http://dx.doi.org/10.1186/1742-2094-9-228 |
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author | Walker, Peter A Bedi, Supinder S Shah, Shinil K Jimenez, Fernando Xue, Hasen Hamilton, Jason A Smith, Philippa Thomas, Chelsea P Mays, Robert W Pati, Shibani Cox, Charles S |
author_facet | Walker, Peter A Bedi, Supinder S Shah, Shinil K Jimenez, Fernando Xue, Hasen Hamilton, Jason A Smith, Philippa Thomas, Chelsea P Mays, Robert W Pati, Shibani Cox, Charles S |
author_sort | Walker, Peter A |
collection | PubMed |
description | INTRODUCTION: We have demonstrated previously that the intravenous delivery of multipotent adult progenitor cells (MAPC) after traumatic brain injury affords neuroprotection via interaction with splenocytes, leading to an increase in systemic anti-inflammatory cytokines. We hypothesize that the observed modulation of the systemic inflammatory milieu is related to T regulatory cells and a subsequent increase in the locoregional neuroprotective M2 macrophage population. METHODS: C57B6 mice were injected with intravenous MAPC 2 and 24 hours after controlled cortical impact injury. Animals were euthanized 24, 48, 72, and 120 hours after injury. In vivo, the proportion of CD4(+)/CD25(+)/FOXP3(+) T-regulatory cells were measured in the splenocyte population and plasma. In addition, the brain CD86(+) M1 and CD206(+) M2 macrophage populations were quantified. A series of in vitro co-cultures were completed to investigate the need for direct MAPC:splenocyte contact as well as the effect of MAPC therapy on M1 and M2 macrophage subtype apoptosis and proliferation. RESULTS: Significant increases in the splenocyte and plasma T regulatory cell populations were observed with MAPC therapy at 24 and 48 hours, respectively. In addition, MAPC therapy was associated with an increase in the brain M2/M1 macrophage ratio at 24, 48 and 120 hours after cortical injury. In vitro cultures of activated microglia with supernatant derived from MAPC:splenocyte co-cultures also demonstrated an increase in the M2/M1 ratio. The observed changes were secondary to an increase in M1 macrophage apoptosis. CONCLUSIONS: The data show that the intravenous delivery of MAPC after cortical injury results in increases in T regulatory cells in splenocytes and plasma with a concordant increase in the locoregional M2/M1 macrophage ratio. Direct contact between the MAPC and splenocytes is required to modulate activated microglia, adding further evidence to the central role of the spleen in MAPC-mediated neuroprotection. |
format | Online Article Text |
id | pubmed-3546881 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-35468812013-01-17 Intravenous multipotent adult progenitor cell therapy after traumatic brain injury: modulation of the resident microglia population Walker, Peter A Bedi, Supinder S Shah, Shinil K Jimenez, Fernando Xue, Hasen Hamilton, Jason A Smith, Philippa Thomas, Chelsea P Mays, Robert W Pati, Shibani Cox, Charles S J Neuroinflammation Research INTRODUCTION: We have demonstrated previously that the intravenous delivery of multipotent adult progenitor cells (MAPC) after traumatic brain injury affords neuroprotection via interaction with splenocytes, leading to an increase in systemic anti-inflammatory cytokines. We hypothesize that the observed modulation of the systemic inflammatory milieu is related to T regulatory cells and a subsequent increase in the locoregional neuroprotective M2 macrophage population. METHODS: C57B6 mice were injected with intravenous MAPC 2 and 24 hours after controlled cortical impact injury. Animals were euthanized 24, 48, 72, and 120 hours after injury. In vivo, the proportion of CD4(+)/CD25(+)/FOXP3(+) T-regulatory cells were measured in the splenocyte population and plasma. In addition, the brain CD86(+) M1 and CD206(+) M2 macrophage populations were quantified. A series of in vitro co-cultures were completed to investigate the need for direct MAPC:splenocyte contact as well as the effect of MAPC therapy on M1 and M2 macrophage subtype apoptosis and proliferation. RESULTS: Significant increases in the splenocyte and plasma T regulatory cell populations were observed with MAPC therapy at 24 and 48 hours, respectively. In addition, MAPC therapy was associated with an increase in the brain M2/M1 macrophage ratio at 24, 48 and 120 hours after cortical injury. In vitro cultures of activated microglia with supernatant derived from MAPC:splenocyte co-cultures also demonstrated an increase in the M2/M1 ratio. The observed changes were secondary to an increase in M1 macrophage apoptosis. CONCLUSIONS: The data show that the intravenous delivery of MAPC after cortical injury results in increases in T regulatory cells in splenocytes and plasma with a concordant increase in the locoregional M2/M1 macrophage ratio. Direct contact between the MAPC and splenocytes is required to modulate activated microglia, adding further evidence to the central role of the spleen in MAPC-mediated neuroprotection. BioMed Central 2012-09-28 /pmc/articles/PMC3546881/ /pubmed/23020860 http://dx.doi.org/10.1186/1742-2094-9-228 Text en Copyright ©2012 Walker et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Walker, Peter A Bedi, Supinder S Shah, Shinil K Jimenez, Fernando Xue, Hasen Hamilton, Jason A Smith, Philippa Thomas, Chelsea P Mays, Robert W Pati, Shibani Cox, Charles S Intravenous multipotent adult progenitor cell therapy after traumatic brain injury: modulation of the resident microglia population |
title | Intravenous multipotent adult progenitor cell therapy after traumatic brain injury: modulation of the resident microglia population |
title_full | Intravenous multipotent adult progenitor cell therapy after traumatic brain injury: modulation of the resident microglia population |
title_fullStr | Intravenous multipotent adult progenitor cell therapy after traumatic brain injury: modulation of the resident microglia population |
title_full_unstemmed | Intravenous multipotent adult progenitor cell therapy after traumatic brain injury: modulation of the resident microglia population |
title_short | Intravenous multipotent adult progenitor cell therapy after traumatic brain injury: modulation of the resident microglia population |
title_sort | intravenous multipotent adult progenitor cell therapy after traumatic brain injury: modulation of the resident microglia population |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3546881/ https://www.ncbi.nlm.nih.gov/pubmed/23020860 http://dx.doi.org/10.1186/1742-2094-9-228 |
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