Polarized Macrophages Have Distinct Roles in the Differentiation and Migration of Embryonic Spinal-cord-derived Neural Stem Cells After Grafting to Injured Sites of Spinal Cord.
Polarized Macrophages Have Distinct Roles in the Differentiation and Migration of Embryonic Spinal-cord-derived Neural Stem Cells After Grafting to Injured Sites of Spinal Cord.
复制标题
极化巨噬细胞在胚胎脊髓源性神经干细胞移植到脊髓损伤部位后的分化和迁移中具有独特的作用
DOI：
10.1038/mt.2015.46
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发表时间：
2015-06
期刊：
影响因子：
--
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Zhang K;Zheng J;Bian G;Liu L;Xue Q;Liu F;Yu C;Zhang H;Song B;Chung SK;Ju G;Wang J
由于中枢神经系统（CNS）的神经元再生受到限制，脊髓损伤（SCI）经常引起严重的不良后果。因此，为神经干细胞/祖细胞（NS/PCs）的移植治疗创造一个允许的环境是一种很有前途的策略，可以替代丢失的神经细胞，促进修复，并刺激脊髓损伤后的功能可塑性。巨噬细胞是重要的sci相关炎症细胞，也是改变病变环境的分泌因子的主要来源。本研究采用骨髓源性M1或M2极化巨噬细胞条件培养基（CM）培养小鼠NS/PCs。在M1-和M2-CM的存在下，NS/PCs显示星形细胞与神经元/少突胶质细胞的分化增强。同样，将NS/ pc与M1和M2巨噬细胞共移植到完整或损伤的小鼠脊髓中，分别增加了NS/ pc来源的星形胶质细胞和神经元/少突胶质细胞的数量。此外，当与M2巨噬细胞共移植时，NS/ pc来源的神经元融入局部电路并增强脊髓损伤后的运动恢复。有趣的是，移植的M1巨噬细胞以趋化因子（C-X-C motif）受体4 （CXCR4）依赖的方式促进NS/ pc源性细胞的远距离吻侧迁移，而移植的M2巨噬细胞导致NS/ pc源性细胞的细胞迁移有限。综上所述，这些发现表明，NS/PCs与极化巨噬细胞的共移植可能是一种很有前景的脊髓损伤修复治疗方法。
Spinal cord injury (SCI) frequently provokes serious detrimental outcomes because neuronal regeneration is limited in the central nervous system (CNS). Thus, the creation of a permissive environment for transplantation therapy with neural stem/progenitor cells (NS/PCs) is a promising strategy to replace lost neuronal cells, promote repair, and stimulate functional plasticity after SCI. Macrophages are important SCI-associated inflammatory cells and a major source of secreted factors that modify the lesion milieu. Here, we used conditional medium (CM) from bone marrow-derived M1 or M2 polarized macrophages to culture murine NS/PCs. The NS/PCs showed enhanced astrocytic versus neuronal/oligodendrocytic differentiation in the presence of M1- versus M2-CM. Similarly, cotransplantation of NS/PCs with M1 and M2 macrophages into intact or injured murine spinal cord increased the number of engrafted NS/PC-derived astrocytes and neurons/oligodendrocytes, respectively. Furthermore, when cotransplantated with M2 macrophages, the NS/PC-derived neurons integrated into the local circuitry and enhanced locomotor recovery following SCI. Interesting, engrafted M1 macrophages promoted long-distance rostral migration of NS/PC-derived cells in a chemokine (C-X-C motif) receptor 4 (CXCR4)-dependent manner, while engrafted M2 macrophages resulted in limited cell migration of NS/PC-derived cells. Altogether, these findings suggest that the cotransplantation of NS/PCs together with polarized macrophages could constitute a promising therapeutic approach for SCI repair.