Transplantation of Mesenchymal Stem Cells Promotes an Alternative Pathway of Macrophage Activation and Functional Recovery after Spinal Cord Injury
Transplantation of Mesenchymal Stem Cells Promotes an Alternative Pathway of Macrophage Activation and Functional Recovery after Spinal Cord Injury
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DOI：
10.1089/neu.2011.2109
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发表时间：
2012-05-01
影响因子：
4.2
通讯作者：
Baba, Hisatoshi
中科院分区：
文献类型：
--
作者：
Nakajima, Hideaki;Uchida, Kenzo;Baba, Hisatoshi
来源于骨髓的间充质干细胞（MSC）可以潜在地减轻脊髓损伤（SCI）的急性炎症反应，从而促进功能恢复。然而，移植MSC减轻SCI后炎症的确切机制仍不清楚。本研究旨在研究MSC移植的效果，特别关注其对SCI后巨噬细胞活化的影响。通过挫伤使大鼠遭受T9-T10 SCI，然后在3天后将1.0 × 10（6）PKH 26标记的MSC移植到挫伤中心进行治疗。移植的MSC在损伤的脊髓内迁移，而不分化成胶质细胞或神经元成分。MSC移植与SCI环境的显著变化相关，IL-4和IL-13水平显著升高，TNF-α和IL-6水平降低。这与交替活化的巨噬细胞（M2表型：iNOS-1或CD 206阳性）数量增加和经典活化的巨噬细胞（M1表型：iNOS或CD 16/32阳性）数量减少同时相关。这些变化与MSC移植组的功能性运动恢复有关，这与保留的轴突、较少的瘢痕组织形成和增加的髓鞘保留有关。我们的结果表明，SCI后急性移植MSC通过将巨噬细胞表型从M1转移到M2来改变炎症环境，这可能会减少损伤后亚急性/慢性期抑制性疤痕组织的影响，为轴突延伸和功能恢复提供一个宽松的环境。
Mesenchymal stem cells (MSC) derived from bone marrow can potentially reduce the acute inflammatory response in spinal cord injury (SCI) and thus promote functional recovery. However, the precise mechanisms through which transplanted MSC attenuate inflammation after SCI are still unclear. The present study was designed to investigate the effects of MSC transplantation with a special focus on their effect on macrophage activation after SCI. Rats were subjected to T9-T10 SCI by contusion, then treated 3 days later with transplantation of 1.0 x 10(6) PKH26-labeled MSC into the contusion epicenter. The transplanted MSC migrated within the injured spinal cord without differentiating into glial or neuronal elements. MSC transplantation was associated with marked changes in the SCI environment, with significant increases in IL-4 and IL-13 levels, and reductions in TNF-alpha and IL-6 levels. This was associated simultaneously with increased numbers of alternatively activated macrophages (M2 phenotype: arginase-1- or CD206-positive), and decreased numbers of classically activated macrophages (M1 phenotype: iNOS- or CD16/32-positive). These changes were associated with functional locomotion recovery in the MSC-transplanted group, which correlated with preserved axons, less scar tissue formation, and increased myelin sparing. Our results suggested that acute transplantation of MSC after SCI modified the inflammatory environment by shifting the macrophage phenotype from M1 to M2, and that this may reduce the effects of the inhibitory scar tissue in the subacute/chronic phase after injury to provide a permissive environment for axonal extension and functional recovery.