Walczak Piotr, Wojtkiewicz Joanna, Nowakowski Adam, Habich Aleksandra, Holak Piotr, Xu Jiadi, Adamiak Zbigniew, Chehade Moussa, Pearl Monica S, Gailloud Philippe, Lukomska Barbara, Maksymowicz Wojciech, Bulte Jeff Wm, Janowski Miroslaw
1 Division of MR Research, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
2 Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
J Cereb Blood Flow Metab. 2017 Jul;37(7):2346-2358. doi: 10.1177/0271678X16665853. Epub 2016 Jan 1.
Stem cell therapy for neurological disorders reached a pivotal point when the efficacy of several cell types was demonstrated in small animal models. Translation of stem cell therapy is contingent upon overcoming the challenge of effective cell delivery to the human brain, which has a volume ∼1000 times larger than that of the mouse. Intra-arterial injection can achieve a broad, global, but also on-demand spatially targeted biodistribution; however, its utility has been limited by unpredictable cell destination and homing as dictated by the vascular territory, as well as by safety concerns. We show here that high-speed MRI can be used to visualize the intravascular distribution of a superparamagnetic iron oxide contrast agent and can thus be used to accurately predict the distribution of intra-arterial administered stem cells. Moreover, high-speed MRI enables the real-time visualization of cell homing, providing the opportunity for immediate intervention in the case of undesired biodistribution.
当几种细胞类型在小动物模型中显示出疗效时,神经疾病的干细胞治疗达到了一个关键节点。干细胞治疗的转化取决于克服将有效细胞输送到人类大脑这一挑战,人类大脑的体积比小鼠大脑大1000倍左右。动脉内注射可以实现广泛、全局但也可按需进行空间靶向的生物分布;然而,其效用受到血管区域所决定的不可预测的细胞归宿和归巢以及安全问题的限制。我们在此表明,高速MRI可用于可视化超顺磁性氧化铁造影剂的血管内分布,因此可用于准确预测动脉内注射干细胞的分布。此外,高速MRI能够实时可视化细胞归巢,为在生物分布不理想的情况下立即进行干预提供了机会。