Intravenous multipotent adult progenitor cell treatment decreases inflammation leading to functional recovery following spinal cord injury.
Intravenous multipotent adult progenitor cell treatment decreases inflammation leading to functional recovery following spinal cord injury.
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DOI：
10.1038/srep16795
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发表时间：
2015-11-19
影响因子：
4.6
通讯作者：
Silver J
中科院分区：
文献类型：
--
作者：
DePaul MA;Palmer M;Lang BT;Cutrone R;Tran AP;Madalena KM;Bogaerts A;Hamilton JA;Deans RJ;Mays RW;Busch SA;Silver J
脊髓损伤(SCI)后，免疫介导的次级过程加剧了永久性神经功能障碍的程度。我们研究了成人骨髓干细胞在脊髓损伤后改变炎症和促进恢复的能力，这种干细胞具有免疫调节特性。在体外，我们发现人多能成体祖细胞(MAPC)具有调节巨噬细胞激活的能力，预先暴露于MAPC分泌的因子可以减少巨噬细胞介导的营养不良轴突的轴突死亡。使用脊髓损伤的挫伤模型，我们发现脊髓损伤后一天静脉注射MAPC，但不是立即，显著改善尿液和运动恢复，这与明显保留脊髓组织有关。静脉注射MAPC改变了脊髓和外周的免疫反应，然而生物分布研究表明，在脊髓中没有发现MAPC，而是优先定位于脾。我们的结果表明MAPC在外周发挥其主要作用，并为这些细胞在急性人挫伤脊髓损伤中的应用提供了强有力的支持。
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.