Mesenchymal stem cell-educated macrophages: a novel type of alternatively activated macrophages.

Mesenchymal stem cell-educated macrophages: a novel type of alternatively activated macrophages.
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DOI:
10.1016/j.exphem.2009.09.004
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发表时间:
2009-12
影响因子:
2.6
通讯作者:
Hematti, Peiman
Hematti, Peiman
中科院分区:
医学4区
文献类型:
--
作者:
Kim, Jaehyup;Hematti, Peiman

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间充质干细胞(MSC)能够通过与广泛的免疫细胞相互作用来调节免疫系统。本研究探讨了MSC与巨噬细胞的相互作用可能在其抗炎/免疫调节作用中发挥重要作用的假设。MSC来源于骨髓,单核细胞分离自健康供体的外周血。我们培养人单核细胞7天,不添加任何细胞因子以产生巨噬细胞,然后将其与培养扩增的MSC共培养3天。我们使用细胞表面抗原表达和细胞内细胞因子表达模式来研究在此共培养期结束时巨噬细胞的免疫表型,并通过吞噬试验来研究其体外功能活性。与MSC共培养的巨噬细胞一致地显示出高水平的CD 206表达,CD 206是交替活化的巨噬细胞的标志物。此外,这些巨噬细胞表达高水平的IL-10和低水平的IL-12,如通过细胞内染色所确定的,这是交替活化的巨噬细胞的典型特征。然而,与对照相比,与MSC共培养的巨噬细胞也表达高水平的IL-6和低水平的TNF-α。在功能上,与MSC共培养的巨噬细胞显示出更高水平的吞噬活性。我们描述了一种新型的人巨噬细胞与MSC共培养后在体外产生,假设免疫表型定义为IL-10高,IL-12低,IL-6高和TNF-α低分泌细胞。这些MSC-教育的巨噬细胞可能是一种独特的和新型的替代活化的巨噬细胞,在组织修复中具有潜在的重要作用。
Mesenchymal stem cells (MSCs) are capable of modulating the immune system through interaction with a wide range of immune cells. This study investigates the hypothesis that interaction of MSCs with macrophages could play a significant role in their anti-inflammatory/immune modulatory effects. MSCs were derived from bone marrow and monocytes were isolated from peripheral blood of healthy donors. We cultured human monocytes for seven days without any added cytokines to generate macrophages, and then co-cultured them for three more days with culture-expanded MSCs. We used cell surface antigen expression and intracellular cytokine expression patterns to study the immunophenotype of macrophages at the end of this co-culture period, and phagocytic assays to investigate their functional activity in vitro. Macrophages co-cultured with MSCs consistently showed high level expression of CD206, a marker of alternatively activated macrophages. Furthermore, these macrophages expressed high levels of IL-10 and low levels of IL-12, as determined by intracellular staining, typical of alternatively activated macrophages. However, macrophages co-cultured with MSCs also expressed high levels of IL-6 and low levels of TNF-α, compared to controls. Functionally, macrophages co-cultured with MSCs showed a higher level of phagocytic activity. We describe a novel type of human macrophage generated in vitro after co-culture with MSCs that assume an immunophenotype defined as IL-10 high, IL-12 low, IL-6 high and TNF-α low secreting cells. These MSC-educated macrophages may be a unique and novel type of alternatively activated macrophages with potentially significant role in tissue repair.
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作者:
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