Mesenchymal Stem Cells Modulate the Functional Properties of Microglia via TGF-β Secretion
Mesenchymal Stem Cells Modulate the Functional Properties of Microglia via TGF-β Secretion
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DOI：
10.5966/sctm.2015-0217
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发表时间：
2016-11-01
影响因子：
6
通讯作者：
Kim, Seung Hyun
中科院分区：
文献类型：
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作者：
Noh, Min Young;Lim, Su Min;Kim, Seung Hyun
小胶质细胞表型的调节是神经退行性疾病的潜在治疗干预。以前，我们报道了间充质基质细胞（MSC）中的转化生长因子-β（TGF-β）水平可作为潜在的生物标志物来预测肌萎缩侧索硬化症患者自体MSC治疗的有效性。然而，在确定小胶质细胞的功能特性时，MSC中TGF-β的潜在机制尚未完全阐明。在这项研究中，我们的目的是阐明TGF-β参与MSC有效性的作用，特别是关注在神经炎症中发挥关键作用的小胶质细胞功能特性。我们发现，MSC条件培养基（MSC-CM）抑制促炎细胞因子的表达，恢复替代活化小胶质细胞表型标志物（fractalkine受体，甘露糖受体，CD 200受体），并增强脂多糖（LPS）刺激的小胶质细胞的吞噬作用。此外，MSC-CM中的TGF-β通过抑制核因子-κ B通路和恢复LPS刺激的小胶质细胞中的TGF-β通路在这些效应中发挥主要作用。重组TGF-β在LPS刺激的小胶质细胞中也诱导了与MSC-CM相似的作用。因此，我们提出，骨髓间充质干细胞可以通过TGF-β分泌调节小胶质细胞的功能特性，将它们从经典的活化表型转换为炎症消退表型。后者的作用可能与抑制神经退行性疾病中的神经炎症过程有关。
The regulation of microglial cell phenotype is a potential therapeutic intervention in neurodegenerative disease. Previously, we reported that transforming growth factor-beta (TGF-beta) levels in mesenchymal stromal cells (MSCs) could be used as potential biological markers to predict the effectiveness of autologous MSC therapy in patients with amyotrophic lateral sclerosis. However, the underlying mechanism of TGF-beta in MSCs was not fully elucidated in determining the functional properties of microglia. In this study, we aimed to clarify the role of TGF-beta that is involved in MSC effectiveness, especially focusing on microglia functional properties that play a pivotal role in neuroinflammation. We found that MSC-conditioned media (MSC-CM) inhibited proinflammatory cytokine expression, restored alternative activated microglia phenotype markers (fractalkine receptor, mannose receptor, CD200 receptor), and enhanced phagocytosis in lipopolysaccharide (LPS)-stimulated microglia. In addition, TGF-beta in MSC-CM played a major role in these effects by inhibiting the nuclear factor-kappa B pathway and restoring the TGF-beta pathway in LPS-stimulated microglia. Recombinant TGF-beta also induced similar effects to MSC-CM in LPS-stimulated microglia. Therefore, we propose that MSCs can modulate the functional properties of microglia via TGF-beta secretion, switching them from a classically activated phenotype to an inflammation-resolving phenotype. The latter role may be associated with the inhibition of neuroinflammatory processes in neurodegenerative disorders.