Department of Neurosurgery, Brigham & Women's Hospital, Harvard Medical School, 221 Longwood Ave, Rm 121, Boston, MA 02115, USA.
J Neurooncol. 2012 Apr;107(2):257-67. doi: 10.1007/s11060-011-0754-7. Epub 2011 Nov 12.
Human mesenchymal stromal cells (hMSC) can be used as a drug delivery vehicle for the treatment of GBM. However, tracking the migration and distribution of these transplanted cells is necessary to interpret therapeutic efficacy. We compared three labeling techniques for their ability to track the migration of transplanted hMSC in an orthotopic mouse xenograft model. hMSC were labeled with three different imaging tags (fluorescence, luciferase or ferumoxide) for imaging by fluorescence, bioluminescence or magnetic resonance imaging (MRI), respectively. hMSC were labeled for all imaging modalities without the use of transfection agents. The labeling efficacy of the tags was confirmed, followed by in vitro and in vivo migration assays to track hMSC migration towards U87 glioma cells. Our results confirmed that the labeled hMSC retained their migratory ability in vitro, similar to unlabeled hMSC. In addition, labeled hMSC migrated towards the U87 tumor site, demonstrating their retention of tumor tropism. hMSC tumor tropism was confirmed by all three imaging modalities; however, MRI provides both real time assessment and the high resolution needed for clinical studies. Our findings suggest that ferumoxide labeling of hMSC is feasible, does not alter their migratory ability and allows detection by MRI. Non invasive tracking of transplanted therapeutic hMSC in the brain will allow further development of human cell based therapies.
人骨髓基质细胞(hMSC)可用作治疗 GBM 的药物输送载体。然而,为了评估治疗效果,有必要对这些移植细胞的迁移和分布进行跟踪。我们比较了三种标记技术,以评估它们在原位小鼠异种移植模型中追踪移植 hMSC 迁移的能力。hMSC 分别用三种不同的成像标签(荧光、荧光素酶或超顺磁性氧化铁)进行标记,以便通过荧光、生物发光或磁共振成像(MRI)进行成像。hMSC 未经转染剂即可用于所有成像方式进行标记。确认了标签的标记效率,然后进行体外和体内迁移实验以追踪 hMSC 向 U87 神经胶质瘤细胞的迁移。我们的结果证实,标记的 hMSC 在体外保持其迁移能力,与未标记的 hMSC 相似。此外,标记的 hMSC 向 U87 肿瘤部位迁移,表明其保留了肿瘤趋向性。三种成像方式均证实了 hMSC 的肿瘤趋向性;然而,MRI 提供了实时评估和临床研究所需的高分辨率。我们的研究结果表明,hMSC 的超顺磁性氧化铁标记是可行的,不会改变其迁移能力,并可通过 MRI 检测。对脑内移植治疗性 hMSC 的非侵入性追踪将进一步推动基于人类细胞的治疗方法的发展。