Mesenchymal stem cells rescue injured endothelial cells in an in vitro ischemia-reperfusion model via tunneling nanotube like structure-mediated mitochondrial transfer
Mesenchymal stem cells rescue injured endothelial cells in an in vitro ischemia-reperfusion model via tunneling nanotube like structure-mediated mitochondrial transfer
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DOI：
10.1016/j.mvr.2014.01.008
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发表时间：
2014-03-01
影响因子：
3.1
通讯作者：
Yan, Chuanzhu
中科院分区：
文献类型：
--
作者：
Liu, Kaiming;Ji, Kunqian;Yan, Chuanzhu
间充质干细胞可作为缺血性血管疾病的一种新的治疗方法，但其治疗效果和作用机制需要进一步评价。线粒体功能障碍在微血管网缺血再灌注损伤中具有核心作用。最近的一项发现表明，使用隧道纳米管的细胞间通讯可以在相邻细胞之间转移线粒体。本研究旨在探讨干细胞介导的线粒体拯救受损血管内皮细胞的隧道纳米管机制。使用激光扫描共聚焦显微镜，检测到间充质干细胞和人脐静脉内皮细胞之间通过隧道纳米管样结构进行线粒体转移。在人脐静脉内皮细胞上进行氧葡萄糖剥夺和再氧合，其通过隧穿纳米管样结构诱导线粒体转移，从而从间充质干细胞到受损的内皮细胞变得频繁且几乎单向，从而导致有氧呼吸的拯救和内皮细胞免于凋亡的保护。我们发现，隧道纳米管样结构的形成可能代表了通过暴露在凋亡内皮细胞表面的磷脂酰丝氨酸和干细胞识别的防御和救援机制。我们的数据提供的证据表明，干细胞可以通过一种尚未确定的机制拯救受损的血管内皮细胞。(C)2014 Elsevier Inc. All rights reserved.
Mesenchymal stem cells can be used as a novel treatment of ischemic vascular disease; however, their therapeutic effect and mechanism of action require further evaluation. Mitochondrial dysfunction has core functions in ischemia-reperfusion injury of the microvascular network. A recent discovery has shown that intercellular communication using tunneling nanotubes can transfer mitochondria between adjacent cells. This study aimed to investigate the tunneling nanotube mechanisms that might be involved in stem cell-mediated mitochondrial rescue of injured vascular endothelial cells. Using laser scanning confocal microscopy, mitochondrial transfer via a tunneling nanotube-like structure was detected between mesenchymal stem cells and human umbilical vein endothelial cells. Oxygen glucose deprivation and reoxygenation were performed on human umbilical vein endothelial cells, which induced mitochondrial transfer through tunneling nanotube-like structures to become frequent and almost unidirectional from mesenchymal stem cells to injured endothelial cells, thereby resulting in the rescue of aerobic respiration and protection of endothelial cells from apoptosis. We found that the formation of tunneling nanotube-like structures might represent a defense and rescue mechanism through phosphatidylserines exposed on the surface of apoptotic endothelial cells and stem cell recognition. Our data provided evidence that stem cells can rescue damaged vascular endothelial cells through a mechanism that has not yet been identified. (C) 2014 Elsevier Inc. All rights reserved.