Division of Biomedical Engineering, Department of Medicine, Center for Regenerative Therapeutics, Brigham and Women's Hospital, Harvard Medical School, Harvard Stem Cell Institute, Harvard-MIT, Division of Health Sciences and Technology, 65 Landsdowne Street, Cambridge, Massachusetts 02139, USA.
Nano Lett. 2012 Aug 8;12(8):4131-9. doi: 10.1021/nl301658q. Epub 2012 Jul 12.
Monitoring the location, distribution and long-term engraftment of administered cells is critical for demonstrating the success of a cell therapy. Among available imaging-based cell tracking tools, magnetic resonance imaging (MRI) is advantageous due to its noninvasiveness, deep penetration, and high spatial resolution. While tracking cells in preclinical models via internalized MRI contrast agents (iron oxide nanoparticles, IO-NPs) is a widely used method, IO-NPs suffer from low iron content per particle, low uptake in nonphagocytotic cell types (e.g., mesenchymal stem cells, MSCs), weak negative contrast, and decreased MRI signal due to cell proliferation and cellular exocytosis. Herein, we demonstrate that internalization of IO-NP (10 nm) loaded biodegradable poly(lactide-co-glycolide) microparticles (IO/PLGA-MPs, 0.4-3 μm) in MSCs enhances MR parameters such as the r(2) relaxivity (5-fold), residence time inside the cells (3-fold) and R(2) signal (2-fold) compared to IO-NPs alone. Intriguingly, in vitro and in vivo experiments demonstrate that internalization of IO/PLGA-MPs in MSCs does not compromise inherent cell properties such as viability, proliferation, migration and their ability to home to sites of inflammation.
监测给药细胞的位置、分布和长期植入情况对于证明细胞治疗的成功至关重要。在现有的基于成像的细胞跟踪工具中，磁共振成像（MRI）具有非侵入性、深穿透和高空间分辨率的优势。虽然通过内化 MRI 对比剂（氧化铁纳米颗粒，IO-NPs）在临床前模型中跟踪细胞是一种广泛使用的方法，但 IO-NPs 存在每颗粒铁含量低、非吞噬细胞类型（例如间充质干细胞，MSCs）摄取率低、负对比弱以及由于细胞增殖和细胞胞吐作用导致 MRI 信号减弱等问题。在这里，我们证明了 IO-NP（10nm）负载在可生物降解的聚（乳酸-共-乙醇酸）微颗粒（IO/PLGA-MPs，0.4-3μm）中的内化可以增强 MR 参数，例如 r(2)弛豫率（提高 5 倍）、细胞内停留时间（提高 3 倍）和 R(2)信号（提高 2 倍），与单独的 IO-NPs 相比。有趣的是，体外和体内实验表明，IO/PLGA-MPs 在 MSCs 中的内化不会损害细胞的固有特性，如活力、增殖、迁移以及它们向炎症部位归巢的能力。
