Interleukin 6 Plays a Role in the Migration of Magnetically Levitated Mesenchymal Stem Cells Spheroids
Interleukin 6 Plays a Role in the Migration of Magnetically Levitated Mesenchymal Stem Cells Spheroids
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DOI：
10.3390/app8030412
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发表时间：
2018-03-01
影响因子：
2.7
通讯作者：
Berry, Catherine Cecilia
中科院分区：
文献类型：
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作者：
Casson, Jake;O'Kane, Sam;Berry, Catherine Cecilia
间充质干细胞(MSCs)静静地驻留在骨髓中一个特殊的“利基”环境中。然而，在适当的信号提示下，MSCs动员并从利基中迁移出来，通常是朝着损伤部位(再生反应)或原发肿瘤(一种内在的归巢反应，促进MSCs作为细胞载体进行治疗)迁移。到目前为止，人们对MSC的动员知之甚少。通过采用3D MSC生态位模型，即MSC球体在I型胶原凝胶中培养，最近的研究强调白细胞介素6(IL-6)是参与MSC迁移的关键细胞因子。在此，我们进一步研究了IL-6诱导MSC迁移的能力，并确定了影响细胞动员的关键基质金属蛋白酶。简而言之，IL-6对MSC在二维模型系统中迁移的影响进行了表征-既使用Ibiti趋化平板阵列(评估定向迁移)，然后通过标准的2D单层实验，在培养细胞中用IL-6挑战并使用Abcam人基质金属蛋白酶膜抗体阵列测试提取的培养液。2D实验显示对IL-6有很强的迁移反应，对膜阵列数据的分析显示几种关键的MMPs显著增加。两组数据都表明IL-6在骨髓间充质干细胞的动员和迁移中起重要作用。我们还研究了在3D球体培养中诱导IL-6对MSCs的影响，作为骨髓利基的简化模型，其特征是荧光标记的磁性纳米颗粒和相同的膜抗体阵列。1 ng/mLIL-6处理的细胞分泌的基质金属蛋白酶水平比对照条件下增加，此外，细胞从中央椭圆形团块迁移出去。
Mesenchymal stem cells (MSCs) reside quiescently within a specialised 'niche' environment in the bone marrow. However, following appropriate signalling cues, MSCs mobilise and migrate out from the niche, typically toward either sites of injury (a regenerative response) or toward primary tumours (an intrinsic homing response, which promotes MSCs as cellular vectors for therapeutic delivery). To date, very little is known about MSC mobilisation. By adopting a 3D MSC niche model, whereby MSC spheroids are cultured within a type I collagen gel, recent studies have highlighted interleukin-6 (IL-6) as a key cytokine involved in MSC migration. Herein, the ability of IL-6 to induce MSC migration was further investigated, and the key matrix metalloproteinases used to effect cell mobilisation were identified. Briefly, the impact of IL-6 on the MSC migration in a two-dimensional model systems was characterised-both visually using an Ibidi chemotaxis plate array (assessing for directional migration) and then via a standard 2D monolayer experiment, where cultured cells were challenged with IL-6 and extracted media tested using an Abcam Human MMP membrane antibody array. The 2D assay displayed a strong migratory response toward IL-6 and analysis of the membrane arrays data showed significant increases of several key MMPs. Both data sets indicated that IL-6 is important in MSC mobilisation and migration. We also investigated the impact of IL-6 induction on MSCs in 3D spheroid culture, serving as a simplistic model of the bone marrow niche, characterised by fluorescently tagged magnetic nanoparticles and identical membrane antibody arrays. An increase in MMP levels secreted by cells treated with 1 ng/mL IL-6 versus control conditions was noted in addition to migration of cells away from the central spheroid mass.