Modulation properties of factors released by bone marrow stromal cells on activated microglia: an in vitro study.
Modulation properties of factors released by bone marrow stromal cells on activated microglia: an in vitro study.
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DOI：
10.1038/srep07514
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发表时间：
2014-12-19
影响因子：
4.6
通讯作者：
Salzet M
中科院分区：
文献类型：
--
作者：
Cizkova D;Devaux S;Le Marrec-Croq F;Franck J;Slovinska L;Blasko J;Rosocha J;Spakova T;Lefebvre C;Fournier I;Salzet M
在本文中，我们利用大鼠骨髓基质细胞（BMSCs-CM）的条件培养基，开发了一种新的非细胞基础（无细胞）治疗BV2小胶质细胞和脊髓源性原代小胶质细胞（PM）的方法。首先，我们从幼稚或受伤的大鼠脊髓组织（SCI-CM，炎症刺激剂）和大鼠骨髓基质细胞（BMSCs-CM，治疗性免疫调节剂）中收集条件培养基（CM）。随后使用蛋白质组学分析检查它们是否存在趋化因子和生长、神经营养和神经迁移因子。结果表明，大鼠BMSCs-CM中含有体外生长因子、神经迁移因子、成骨因子、分化因子和免疫调节剂，SCI-CM中含有趋化因子、趋化因子和神经营养因子。随后，我们检测了SCI-CM对BV2或PM细胞的趋化活性、NO生成、形态学和促凋亡变化的影响。我们的研究结果证实了BMSCs-CM对sci - cm激活的小胶质细胞的抗迁移和no抑制作用，对初级小胶质细胞的影响更大。BMSCs-CM的细胞毒性作用仅发生在sci - cm刺激的BV2细胞和PM上，而不发生在初始BV2细胞和PM上。综上所述，在BMSCs-CM中发现的分子鸡尾酒有利于免疫调节特性。
In the present paper we develop a new non-cell based (cell-free) therapeutic approach applied to BV2 microglial cells and spinal cord derived primary microglia (PM) using conditioned media from rat bone marrow stromal cells (BMSCs-CM). First we collected conditioned media (CM) from either naive or injured rat spinal cord tissue (SCI-CM, inflammatory stimulation agent) and from rat bone marrow stromal cells (BMSCs-CM, therapeutic immunomodulation agent). They were both subsequently checked for the presence of chemokines and growth, neurotrophic and neural migration factors using proteomics analysis. The data clearly showed that rat BMSCs-CM contain in vitro growth factors, neural migration factors, osteogenic factors, differentiating factors and immunomodulators, whereas SCI-CM contain chemokines, chemoattractant factors and neurotrophic factors. Afterwards we determined whether the BMSCs-CM affect chemotactic activity, NO production, morphological and pro-apoptotic changes of either BV2 or PM cells once activated with SCI-CM. Our results confirm the anti-migratory and NO-inhibitory effects of BMSCs-CM on SCI-CM-activated microglia with higher impact on primary microglia. The cytotoxic effect of BMSCs-CM occurred only on SCI-CM-stimulated BV2 cells and PM, not on naive BV2 cells, nor on PM. Taken together, the molecular cocktail found in BMSCs-CM is favorable for immunomodulatory properties.