Laboratoire Matière et Systèmes Complexes, UMR 7057, CNRS/Université Paris Diderot, Sorbonne Paris Cité, 75205 Paris cedex 13, France.
Pharm Res. 2012 May;29(5):1392-403. doi: 10.1007/s11095-012-0680-1. Epub 2012 Jan 21.
Cell labeling with magnetic nanoparticles can be used to monitor the fate of transplanted cells in vivo by magnetic resonance imaging. However, nanoparticles initially internalized in administered cells might end up in other cells of the host organism. We investigated a mechanism of intercellular cross-transfer of magnetic nanoparticles to different types of recipient cells via cell microvesicles released under cellular stress.
Three cell types (mesenchymal stem cells, endothelial cells and macrophages) were labeled with 8-nm iron oxide nanoparticles. Then cells underwent starvation stress, during which they produced microvesicles that were subsequently transferred to unlabeled recipient cells.
The analysis of the magnetophoretic mobility of donor cells indicated that magnetic load was partially lost under cell stress. Microvesicles shed by stressed cells participated in the release of magnetic label. Moreover, such microvesicles were uptaken by naïve cells, resulting in cellular redistribution of nanoparticles. Iron load of recipient cells allowed their detection by MRI.
Cell microvesicles released under stress may be disseminated throughout the organism, where they can be uptaken by host cells. The transferred cargo may be sufficient to allow MRI detection of these secondarily labeled cells, leading to misinterpretations of the effectiveness of transplanted cells.
细胞用磁性纳米颗粒标记后，可通过磁共振成像（MRI）来监测移植细胞在体内的命运。然而，最初被摄入细胞内的纳米颗粒可能最终会进入宿主生物的其他细胞。我们研究了一种通过细胞在受到压力时释放的细胞微囊泡，将磁性纳米颗粒从供体细胞转移到不同类型的受体细胞的细胞间交叉转移机制。
用 8nm 的氧化铁纳米颗粒标记三种细胞类型（间充质干细胞、内皮细胞和巨噬细胞）。然后，细胞经历饥饿应激，在此期间，它们产生了随后被转移到未标记的受体细胞的微囊泡。
对供体细胞的磁泳动性分析表明，细胞受到压力时磁性负载部分丢失。受应激细胞释放的微囊泡参与了磁性标记物的释放。此外，这些微囊泡被幼稚细胞摄取，导致纳米颗粒在细胞内重新分布。受体细胞的铁负荷可使其通过 MRI 检测到。
在应激下释放的细胞微囊泡可能会在整个机体中传播，在那里它们可以被宿主细胞摄取。转移的货物可能足以允许对这些二次标记的细胞进行 MRI 检测，从而导致对移植细胞有效性的误解。
