Priming with ceramide-1 phosphate promotes the therapeutic effect of mesenchymal stem/stromal cells on pulmonary artery hypertension
Priming with ceramide-1 phosphate promotes the therapeutic effect of mesenchymal stem/stromal cells on pulmonary artery hypertension
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DOI：
10.1016/j.bbrc.2016.03.046
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发表时间：
2016-04-22
影响因子：
3.1
通讯作者：
Shin, Dong-Myung
中科院分区：
文献类型：
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作者：
Lim, Jisun;Kim, YongHwan;Shin, Dong-Myung
在受损器官中富集的一些分子可以通过刺激干细胞的动员来促进组织修复。这些所谓的“引发”因子包括生物活性脂质、补体成分和阳离子肽。然而，其治疗意义仍有待确定。在这里，我们表明，与神经酰胺-1磷酸（C1 P），一种生物活性脂质，引发的间充质基质/干细胞（MSC），提高其在肺动脉高压（PAH）的治疗效果。与未引发的MSC相比，用100或200 μ M C1 P处理的人骨髓（BM）衍生的MSC在Transwell测定中显示出改善的迁移活性，并伴随激活MAPKP 42/44和Ala信号级联。虽然OP引发对细胞表面标志物表型和MSC的多能性影响不大，但它增强了其增殖、集落形成单位-成纤维细胞和抗炎活性。在野百合碱诱导的PAH动物模型中，单次给予DP致敏的人MSC显著减弱了PAH相关的右心室收缩压、右心室肥大和血管壁周围α-平滑肌肌动蛋白阳性细胞厚度的增加。因此，本研究表明，OP引发通过增强MSC的迁移，自我更新和抗炎活性来增加MSC治疗的效果，并且使用引发方案优化的MSC治疗可能是治疗PAH患者的有希望的选择。(C)2016 Elsevier Inc. All rights reserved.
Some molecules enriched in damaged organs can contribute to tissue repair by stimulating the mobilization of stem cells. These so-called "priming" factors include bioactive lipids, complement components, and cationic peptides. However, their therapeutic significance remains to be determined. Here, we show that priming of mesenchymal stromal/stem cells (MSCs) with ceramide-1 phosphate (C1P), a bioactive lipid, enhances their therapeutic efficacy in pulmonary artery hypertension (PAH). Human bone marrow (BM)-derived MSCs treated with 100 or 200 1.tM C1P showed improved migration activity in Transwell assays compared with non-primed MSCs and concomitantly activated MAPKP42/44 and Ala signaling cascades. Although OP priming had little effect on cell surface marker phenotypes and the multipotency of MSCs, it potentiated their proliferative, colony-forming unit-fibroblast, and anti-inflammatory activities. In a monocrotaline-induced PAH animal model, a single administration of human MSCs primed with DP significantly attenuated the PAH-related increase in right ventricular systolic pressure, right ventricular hypertrophy, and thickness of alpha-smooth muscle actin-positive cells around the vessel wall. Thus, this study shows that OP priming increases the effects of MSC therapy by enhancing the migratory, self-renewal, and anti-inflammatory activity of MSCs and that MSC therapy optimized with priming protocols might be a promising option for the treatment of PAH patients. (C) 2016 Elsevier Inc. All rights reserved.