Purinergic stimulation of human mesenchymal stem cells potentiates their chemotactic response to CXCL12 and increases the homing capacity and production of proinflammatory cytokines
Purinergic stimulation of human mesenchymal stem cells potentiates their chemotactic response to CXCL12 and increases the homing capacity and production of proinflammatory cytokines
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DOI：
10.1016/j.exphem.2010.12.001
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发表时间：
2011-03-01
影响因子：
2.6
通讯作者：
Lemoli, Roberto M.
中科院分区：
文献类型：
--
作者：
Ferrari, Davide;Gulinelli, Sara;Lemoli, Roberto M.
客观的。细胞外三磷酸腺苷 (ATP) 是公认的细胞间通讯介质。在这里，我们展示了 ATP 对骨髓 (BM) 来源的人间充质干细胞 (hMSC) 功能的影响。材料和方法。通过 Affymetrix 技术评估 ATP 诱导的 hMSC 基因表达谱修饰。进行体外克隆形成和迁移测定以及体内异种移植实验，以评估 ATP 对 hMSC 增殖和 BM 归巢的影响。酶联免疫吸附测定用于评估 hMSC 细胞因子的产生，而 T 细胞培养物则证明了 ATP 处理的 hMSC 的免疫调节活性。结果。 hMSC 对 ATP 的细胞毒性作用具有抵抗力，这通过缺乏形态和线粒体变化或细胞死亡的细胞内标记物的释放来证明。基因表达谱显示，ATP 刺激的 hMSC 参与细胞增殖的基因下调，而参与细胞迁移的基因则强烈上调。通过评估克隆基质祖细胞证实了 ATP 对 hMSC 增殖的抑制活性。 ATP 增强了 hMSC 对趋化因子 CXCL12 的趋化反应，并增加了它们的自发迁移。在体内，hMSCs 对免疫缺陷小鼠的 BM 的归巢能力通过 ATP 预处理显着增加。此外，ATP增加促炎细胞因子白细胞介素2、干扰素γ和白细胞介素12p70的产生，同时减少抗炎细胞因子白细胞介素10的产生，这一发现与间充质干细胞抑制T细胞增殖的能力降低有关。结论。我们的数据显示嘌呤能信号调节 hMSC 功能并强调细胞外核苷酸在 hMSC 生物学中的作用。 (C) 2011 ISEH - 血液学和干细胞学会。由爱思唯尔公司出版
Objective. Extracellular adenosine triphosphate (ATP) is a well-recognized mediator of cell-to-cell communication. Here we show ATP effects on bone marrow (BM)-derived human mesenchymal stem cell (hMSCs) functions.Materials and Methods. ATP-induced modification of hMSCs gene expression profile was assessed by Affymetrix technology. Clonogenic and migration assays in vitro, as well as xenotransplant experiments in vivo, were performed to evaluate the effects of ATP on hMSCs proliferation and BM homing. Enzyme-linked immunosorbent assays were used to assess hMSCs cytokines production, whereas T-cell cultures demonstrated the immunoregulatory activity of ATP-treated hMSCs.Results. hMSCs were resistant to the cytotoxic effects of ATP, as demonstrated by the lack of morphological and mitochondrial changes or release of intracellular markers of cell death. Gene expression profiling revealed that ATP-stimulated hMSCs underwent a downregulation of genes involved in cell proliferation, whereas those involved in cell migration were strongly upregulated. The inhibitory activity of ATP on hMSCs proliferation was confirmed by assessing clonogenic stromal progenitors. ATP potentiated the chemotactic response of hMSCs to the chemokine CXCL12, and increased their spontaneous migration. In vivo, the homing capacity of hMSCs to the BM of immunodeficient mice was significantly increased by pretreatment with ATP. Moreover, ATP increased the production of the proinflammatory cytokines interleukin-2, interferon-gamma, and interleukin-12p70, while decreasing the anti-inflammatory cytokine interleukin-10, and this finding was associated with the reduced ability of MSCs to inhibit T-cell proliferation.Conclusions. Our data show that purinergic signaling modulates hMSCs functions and highlights a role for extracellular nucleotides in hMSCs biology. (C) 2011 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.