Frank Laboratory and Laboratory of Diagnostic Radiology Research, Department of Radiology and Imaging Sciences, US National Institutes of Health, Bethesda, Maryland, USA.
Nat Med. 2012 Feb 26;18(3):463-7. doi: 10.1038/nm.2666.
We report on a new straightforward magnetic cell-labeling approach that combines three US Food and Drug Administration (FDA)-approved drugs--ferumoxytol, heparin and protamine--in serum-free medium to form self-assembling nanocomplexes that effectively label cells for in vivo magnetic resonance imaging (MRI). We observed that the ferumoxytol-heparin-protamine (HPF) nanocomplexes were stable in serum-free cell culture medium. HPF nanocomplexes show a threefold increase in T2 relaxivity compared to ferumoxytol. Electron microscopy showed internalized HPF in endosomes, which we confirmed by Prussian blue staining of labeled cells. There was no long-term effect or toxicity on cellular physiology or function of HPF-labeled hematopoietic stem cells, bone marrow stromal cells, neural stem cells or T cells when compared to controls. In vivo MRI detected 1,000 HPF-labeled cells implanted in rat brains. This HPF labeling method should facilitate the monitoring by MRI of infused or implanted cells in clinical trials.
我们报告了一种新的简单的磁细胞标记方法，该方法将三种美国食品和药物管理局（FDA）批准的药物——ferumoxytol、肝素和鱼精蛋白——在无血清培养基中组合形成自组装纳米复合物，有效地标记细胞用于体内磁共振成像（MRI）。我们观察到 ferumoxytol-肝素-鱼精蛋白（HPF）纳米复合物在无血清细胞培养液中稳定。与 ferumoxytol 相比，HPF 纳米复合物的 T2 弛豫率增加了三倍。电子显微镜显示内体内化的 HPF，我们通过标记细胞的普鲁士蓝染色证实了这一点。与对照组相比，HPF 标记的造血干细胞、骨髓基质细胞、神经干细胞或 T 细胞的细胞生理学或功能没有长期影响或毒性。体内 MRI 检测到植入大鼠大脑的 1000 个 HPF 标记细胞。这种 HPF 标记方法应该有助于在临床试验中通过 MRI 监测输注或植入的细胞。
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