Intravenous multipotent adult progenitor cell therapy after traumatic brain injury: modulation of the resident microglia population
<p>Abstract</p> <p>Introduction</p> <p>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 an...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2012-09-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | http://www.jneuroinflammation.com/content/9/1/228 |
| _version_ | 1811312141579321344 |
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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 | DOAJ |
| description | <p>Abstract</p> <p>Introduction</p> <p>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.</p> <p>Methods</p> <p>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. <it>In vivo,</it> the proportion of CD4<sup>+</sup>/CD25<sup>+</sup>/FOXP3<sup>+</sup> T-regulatory cells were measured in the splenocyte population and plasma. In addition, the brain CD86<sup>+</sup> M1 and CD206<sup>+</sup> M2 macrophage populations were quantified. A series of <it>in vitro</it> 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.</p> <p>Results</p> <p>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. <it>In vitro</it> 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.</p> <p>Conclusions</p> <p>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.</p> |
| first_indexed | 2024-04-13T10:31:01Z |
| format | Article |
| id | doaj.art-e6edf81f392941018ee1ce4b1a0d4275 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-04-13T10:31:01Z |
| publishDate | 2012-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-e6edf81f392941018ee1ce4b1a0d42752022-12-22T02:50:10ZengBMCJournal of Neuroinflammation1742-20942012-09-019122810.1186/1742-2094-9-228Intravenous multipotent adult progenitor cell therapy after traumatic brain injury: modulation of the resident microglia populationWalker Peter ABedi Supinder SShah Shinil KJimenez FernandoXue HasenHamilton Jason ASmith PhilippaThomas Chelsea PMays Robert WPati ShibaniCox Charles S<p>Abstract</p> <p>Introduction</p> <p>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.</p> <p>Methods</p> <p>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. <it>In vivo,</it> the proportion of CD4<sup>+</sup>/CD25<sup>+</sup>/FOXP3<sup>+</sup> T-regulatory cells were measured in the splenocyte population and plasma. In addition, the brain CD86<sup>+</sup> M1 and CD206<sup>+</sup> M2 macrophage populations were quantified. A series of <it>in vitro</it> 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.</p> <p>Results</p> <p>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. <it>In vitro</it> 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.</p> <p>Conclusions</p> <p>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.</p>http://www.jneuroinflammation.com/content/9/1/228Multipotent adult progenitor cellsTraumatic brain injuryStem cellsSplenocytesBlood brain barrierMicroglia |
| spellingShingle | 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 Journal of Neuroinflammation Multipotent adult progenitor cells Traumatic brain injury Stem cells Splenocytes Blood brain barrier Microglia |
| 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 | Multipotent adult progenitor cells Traumatic brain injury Stem cells Splenocytes Blood brain barrier Microglia |
| url | http://www.jneuroinflammation.com/content/9/1/228 |
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