Paracrine action of human placental trophoblast cells attenuates cisplatin-induced acute kidney injury
Paracrine action of human placental trophoblast cells attenuates cisplatin-induced acute kidney injury
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DOI：
10.1016/j.lfs.2019.05.054
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发表时间：
2019-08-01
期刊：
影响因子：
6.1
通讯作者：
Zhao, Lei
中科院分区：
文献类型：
--
作者：
Liu, Pengfei;Feng, Yetong;Zhao, Lei
目的：细胞治疗对急性肾损伤（AKI）的作用已被不同的研究小组证实多年。然而，哪种细胞具有最好的治疗效果尚不清楚。在本研究中，我们主要探讨人类胎盘滋养细胞是否具有在AKI治疗中应用的潜力。主要方法：首先从人胎盘中分离滋养细胞，用流式细胞术对其进行鉴定，研究其对肾的保护作用。顺铂诱导NOD-SCID小鼠AKI模型。分别分析人胎盘滋养细胞对肾功能、细胞凋亡和炎症的治疗作用。重点发现：人胎盘分离滋养细胞可改善顺铂所致肾组织病理改变和肾功能障碍。此外，以胎盘滋养层细胞为基础的处理也具有抗凋亡作用，并明显降低了受损肾组织中凋亡基因（Bax和Caspase 3）的表达水平。在胎盘滋养细胞的作用下，肾组织中所有炎症成分（MCP-1、IL-10和RANTES）均下调。进一步分析表明，人胎盘滋养细胞的旁分泌作用可能在AKI治疗过程中起关键作用。意义：在本研究中，我们主要开发了一种新的治疗策略，利用人胎盘滋养细胞治疗顺铂诱导的AKI。尽管这种细胞疗法的详细机制和优化仍需进一步研究，但胎盘滋养细胞的应用在AKI患者的治疗中具有特殊的潜力。
Aims: The action of cell-based therapy against acute kidney injury (AKI) has been demonstrated by different groups for years. However, which kind of cells hold best therapeutic effect remains unclear. In this study, we mainly explored whether human placental trophoblast cells hold the potential to be applied in AKI therapy.Main methods: To study the renoprotective effect, the trophoblast cells were isolated from human placenta and characterized by flow cytometry first. The AKI model was induced using cisplatin in NOD-SCID mice. The therapeutic effect of human placental trophoblast cells on renal function, apoptosis and inflammation were analyzed respectively.Key findings: The administration of trophoblast cells isolated from human placenta improved the pathological changes of kidney tissues and renal dysfunction induced by cisplatin. In addition, the placental trophoblast cell-based treatment also showed anti-apoptotic effect and decreased the level of apoptotic genes (Bax and Caspase 3) expression in damaged kidney tissues obviously. All of the inflammatory components (MCP-1, IL-10 and RANTES) in kidney tissues were down-regulated with the therapy of placental trophoblast cells. Further analysis indicated that the paracrine effects of human placental trophoblast cells may hold a key position in the AKI therapy process.Significance: In this study, we mainly developed a novel therapeutic strategy to treat cisplatin-induced AKI with human placental trophoblast cells. Even though the detailed mechanism and the optimizations of this cell-based therapy still need further investigation, the application of placental trophoblast cell holds special potential in the treatment of patients with AKI.