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用于监测基于细胞的再生医学疗法在肾病模型中的安全性、疗效和作用机制的成像技术。

Imaging technologies for monitoring the safety, efficacy and mechanisms of action of cell-based regenerative medicine therapies in models of kidney disease.

作者信息

Sharkey Jack, Scarfe Lauren, Santeramo Ilaria, Garcia-Finana Marta, Park Brian K, Poptani Harish, Wilm Bettina, Taylor Arthur, Murray Patricia

机构信息

Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GE, UK; Centre for Preclinical Imaging, University of Liverpool, Liverpool L69 3GE, UK.

Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GE, UK.

出版信息

Eur J Pharmacol. 2016 Nov 5;790:74-82. doi: 10.1016/j.ejphar.2016.06.056. Epub 2016 Jul 1.

Abstract

The incidence of end stage kidney disease is rising annually and it is now a global public health problem. Current treatment options are dialysis or renal transplantation, which apart from their significant drawbacks in terms of increased morbidity and mortality, are placing an increasing economic burden on society. Cell-based Regenerative Medicine Therapies (RMTs) have shown great promise in rodent models of kidney disease, but clinical translation is hampered due to the lack of adequate safety and efficacy data. Furthermore, the mechanisms whereby the cell-based RMTs ameliorate injury are ill-defined. For instance, it is not always clear if the cells directly replace damaged renal tissue, or whether paracrine effects are more important. Knowledge of the mechanisms responsible for the beneficial effects of cell therapies is crucial because it could lead to the development of safer and more effective RMTs in the future. To address these questions, novel in vivo imaging strategies are needed to monitor the biodistribution of cell-based RMTs and evaluate their beneficial effects on host tissues and organs, as well as any potential adverse effects. In this review we will discuss how state-of-the-art imaging modalities, including bioluminescence, magnetic resonance, nuclear imaging, ultrasound and an emerging imaging technology called multispectral optoacoustic tomography, can be used in combination with various imaging probes to track the fate and biodistribution of cell-based RMTs in rodent models of kidney disease, and evaluate their effect on renal function.

摘要

终末期肾病的发病率逐年上升,现已成为一个全球性的公共卫生问题。目前的治疗选择是透析或肾移植,这些方法除了在增加发病率和死亡率方面存在重大缺陷外,还给社会带来了日益沉重的经济负担。基于细胞的再生医学疗法(RMTs)在肾病啮齿动物模型中已显示出巨大潜力,但由于缺乏足够的安全性和有效性数据,其临床转化受到阻碍。此外,基于细胞的RMTs改善损伤的机制尚不明确。例如,细胞是否直接替代受损的肾组织,或者旁分泌效应是否更重要,这并不总是清楚的。了解细胞疗法产生有益效果的机制至关重要,因为这可能会在未来促成更安全、更有效的RMTs的开发。为了解决这些问题,需要新的体内成像策略来监测基于细胞的RMTs的生物分布,并评估它们对宿主组织和器官的有益作用以及任何潜在的不良反应。在这篇综述中,我们将讨论如何将包括生物发光、磁共振、核成像、超声以及一种名为多光谱光声断层扫描的新兴成像技术在内的先进成像方式,与各种成像探针结合使用,以追踪基于细胞的RMTs在肾病啮齿动物模型中的命运和生物分布,并评估它们对肾功能的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81cd/5063540/9e8bbae08f53/gr3.jpg

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