Biodistribution of mesenchymal stem cell-derived extracellular vesicles in a model of acute kidney injury monitored by optical imaging.
Biodistribution of mesenchymal stem cell-derived extracellular vesicles in a model of acute kidney injury monitored by optical imaging.
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DOI：
10.3892/ijmm.2014.1663
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发表时间：
2014-05
影响因子：
5.4
通讯作者：
Camussi G
中科院分区：
文献类型：
--
作者：
Grange C;Tapparo M;Bruno S;Chatterjee D;Quesenberry PJ;Tetta C;Camussi G
间充质干细胞（MSCs）有助于组织损伤的恢复，提供旁分泌支持。细胞来源的细胞外囊泡（EVs）携带着细胞起源的膜和细胞质成分，被认为是细胞间通讯的基本机制。我们之前在体内证明了来源于人间充质干细胞的ev加速急性肾损伤（AKI）后的恢复。本研究的目的是探讨急性肾损伤中EVs的生物分布和肾脏定位。为此，采用近红外（NIR）染料（DiD）进行两种适合于光学成像（OI）体内跟踪的EV标记方法：1)用近红外染料预孵育的MSCs产生标记的EV，并从细胞上清中收集；ii)用近红外染料直接标记纯化的电动汽车。将这两种方法获得的EVs静脉注射到甘油诱导AKI小鼠和健康小鼠体内，比较两种标记方法在损伤部位检测EVs的效果。我们发现，与健康对照组相比，AKI小鼠肾脏中标记的ev特异性积累。5小时后，通过两种标记方法，在OI的全身图像和解剖肾脏中都可以检测到ev。直接标记的电动汽车比细胞标记的电动汽车荧光更高、更亮。直接标记的电动汽车产生的信号保持及时，但提供了比细胞产生的标记电动汽车更高的背景。两种方法的比较表明，后者对损伤肾脏表现出更大的特异性。
Mesenchymal stem cells (MSCs) contribute to the recovery of tissue injury, providing a paracrine support. Cell-derived extracellular vesicles (EVs), carrying membrane and cytoplasmatic constituents of the cell of origin, have been described as a fundamental mechanism of intercellular communication. We previously demonstrated that EVs derived from human MSCs accelerated recovery following acute kidney injury (AKI) in vivo. The aim of the present study was to investigate the biodistribution and the renal localization of EVs in AKI. For this purpose, two methods for EV labeling suitable for in vivo tracking with optical imaging (OI), were employed using near infrared (NIR) dye (DiD): i) labeled EVs were generated by MSCs pre-incubated with NIR dye and collected from cell supernatants; ii) purified EVs were directly labeled with NIR dye. EVs obtained with these two procedures were injected intravenously (i.v.) into mice with glycerol-induced AKI and into healthy mice to compare the efficacy of the two labeling methods for in vivo detection of EVs at the site of damage. We found that the labeled EVs accumulated specifically in the kidneys of the mice with AKI compared with the healthy controls. After 5 h, the EVs were detectable in whole body images and in dissected kidneys by OI with both types of labeling procedures. The directly labeled EVs showed a higher and brighter fluorescence compared with the labeled EVs produced by cells. The signal generated by the directly labeled EVs was maintained in time, but provided a higher background than that of the labeled EVs produced by cells. The comparison of the two methods indicated that the latter displayed a greater specificity for the injured kidney.
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影响因子：
3.7
作者：
Collino F;Deregibus MC;Bruno S;Sterpone L;Aghemo G;Viltono L;Tetta C;Camussi G
通讯作者：
Camussi G
影响因子：
20.3
作者：
Deregibus, Maria Chiara;Cantaluppi, Vincenzo;Camussi, Giovanni
通讯作者：
Camussi, Giovanni
影响因子：
6.1
作者：
Gatti, Stefano;Bruno, Stefania;Camussi, Giovanni
通讯作者：
Camussi, Giovanni
影响因子：
5.6
作者：
Jin, Hye Jin;Bae, Yun Kyung;Chang, Jong Wook
通讯作者：
Chang, Jong Wook
影响因子：
3.1
作者：
Boddington, Sophie E.;Sutton, Elizabeth J.;Daldrup-Link, Heike E.
通讯作者：
Daldrup-Link, Heike E.