Delcroix Gaëtan J-R, Jacquart Matthieu, Lemaire Laurent, Sindji Laurence, Franconi Florence, Le Jeune Jean-Jacques, Montero-Menei Claudia N
Inserm, U646, 10 rue André Boquel, Angers, F49100 France.
Brain Res. 2009 Feb 19;1255:18-31. doi: 10.1016/j.brainres.2008.12.013. Epub 2008 Dec 11.
Mesenchymal stem cells (MSC) may transdifferentiate into neural cells in vitro under the influence of matrix molecules and growth factors present in neurogenic niches. However, further experiments on the behavior of such stem cells remain to be done in vivo. In this study, rat MSC (rMSC) have been grafted in a neurogenic environment of the rat brain, the subventricular zone (SVZ), in order to detect and follow their migration using superparamagnetic iron oxide (SPIO) nanoparticles. We sought to characterize the potential effect of iron loading on the behavior of rMSC as well as to address the potential of rMSC to migrate when exposed to the adequate brain microenvironment. 1-hydroxyethylidene-1.1-bisphosphonic acid (HEDP)-coated SPIO nanoparticles efficiently labeled rMSC without significant adverse effects on cell viability and on the in vitro differentiation potential. In opposition to iron-labeled rat neural stem cells (rNSC), used as a positive control, iron-labeled rMSC did not respond to the SVZ microenvironment in vivo and did not migrate, unless a mechanical lesion of the olfactory bulb was performed. This confirmed the known potential of iron-labeled rMSC to migrate toward lesions and, as far as we know, this is the first study describing such a long distance migration from the SVZ toward the olfactory bulb through the rostral migratory stream (RMS).
间充质干细胞(MSC)在神经源性微环境中存在的基质分子和生长因子的影响下,可能在体外转分化为神经细胞。然而,关于此类干细胞行为的进一步实验仍有待在体内进行。在本研究中,将大鼠间充质干细胞(rMSC)移植到大鼠脑的神经源性环境——脑室下区(SVZ),以便使用超顺磁性氧化铁(SPIO)纳米颗粒检测并追踪其迁移。我们试图表征铁负载对rMSC行为的潜在影响,并探讨rMSC在暴露于合适的脑微环境时的迁移潜力。1-羟基亚乙基-1,1-二膦酸(HEDP)包被的SPIO纳米颗粒有效地标记了rMSC,对细胞活力和体外分化潜力没有显著不利影响。与用作阳性对照的铁标记大鼠神经干细胞(rNSC)不同,铁标记的rMSC在体内对SVZ微环境没有反应,也不会迁移,除非对嗅球进行机械损伤。这证实了铁标记的rMSC向损伤部位迁移的已知潜力,据我们所知,这是第一项描述此类从SVZ通过吻侧迁移流(RMS)向嗅球进行长距离迁移的研究。