Intravenous multipotent adult progenitor cell therapy after traumatic brain injury: modulation of the resident microglia population.
Intravenous multipotent adult progenitor cell therapy after traumatic brain injury: modulation of the resident microglia population.
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DOI：
10.1186/1742-2094-9-228
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发表时间：
2012-09-28
影响因子：
9.3
通讯作者：
Cox CS Jr
中科院分区：
文献类型：
--
作者：
Walker PA;Bedi SS;Shah SK;Jimenez F;Xue H;Hamilton JA;Smith P;Thomas CP;Mays RW;Pati S;Cox CS Jr
我们先前已经证明，创伤性脑损伤后静脉内递送多能成体祖细胞（MAPC）通过与脾细胞的相互作用提供神经保护，导致全身性抗炎细胞因子的增加。我们推测，所观察到的全身炎症环境的调制与T调节细胞和随后的局部神经保护性M2巨噬细胞群的增加有关。C57 B6小鼠在受控皮质撞击损伤后2小时和24小时静脉注射MAPC。在损伤后24、48、72和120小时对动物实施安乐死。在体内，在脾细胞群和血浆中测量CD 4 +/CD 25 +/FOXP 3 + T调节细胞的比例。此外，定量脑CD 86 + M1和CD 206 + M2巨噬细胞群。完成一系列体外共培养以研究直接MAPC：脾细胞接触的需要以及MAPC治疗对M1和M2巨噬细胞亚型凋亡和增殖的影响。MAPC治疗分别在24和48小时观察到脾细胞和血浆T调节细胞群的显著增加。此外，MAPC治疗与皮质损伤后24、48和120小时脑M2/M1巨噬细胞比率的增加相关。活化的小胶质细胞与来自MAPC的上清液的体外培养物：脾细胞共培养物也显示M2/M1比率增加。观察到的变化继发于M1巨噬细胞凋亡的增加。数据显示，皮质损伤后MAPC的静脉内递送导致脾细胞和血浆中T调节细胞的增加，伴随局部M2/M1巨噬细胞比率的一致增加。MAPC和脾细胞之间的直接接触是调节活化的小胶质细胞所必需的，这进一步证明了脾在MAPC介导的神经保护中的中心作用。
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. 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. 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. 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.
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影响因子：
3.8
作者：
Harting, Matthew T.;Jimenez, Fernando;Adams, Sasha D.;Mercer, David W.;Cox, Charles S., Jr.
通讯作者：
Cox, Charles S., Jr.
影响因子：
4.5
作者：
Kovacsovics-Bankowski, M.;Mauch, K.;Van't Hof, W.
通讯作者：
Van't Hof, W.
影响因子：
4.4
作者：
Olson, JK;Miller, SD
通讯作者：
Miller, SD
DOI：
10.1523/jneurosci.3257-09.2009
发表时间：
2009-10-28
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Kigerl KA;Gensel JC;Ankeny DP;Alexander JK;Donnelly DJ;Popovich PG
通讯作者：
Popovich PG
DOI：
10.1016/j.nurt.2010.07.002
发表时间：
2010-10
期刊：
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics
影响因子：
--
作者：
Loane DJ;Byrnes KR
通讯作者：
Byrnes KR