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经微创超声引导肾动脉注射向肾脏递送干细胞在小鼠中。

Stem cell delivery to kidney via minimally invasive ultrasound-guided renal artery injection in mice.

机构信息

UCL Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, London, WC1E 6DD, UK.

Department of Medical Physics & Biomedical Engineering, University College London, London, UK.

出版信息

Sci Rep. 2020 May 5;10(1):7514. doi: 10.1038/s41598-020-64417-2.

Abstract

Cell-based therapies are promising treatments for various kidney diseases. However, the major hurdle in initiating therapeutic responses is the inefficiency of injection routes to deliver cells to the kidney parenchyma. Systemic injection, such as intravenous injection only delivers a small proportion of cells to the kidney. Whereas direct delivery, such as renal artery injection requires surgical procedures. A minimally invasive renal artery injection was therefore developed to enhance cell delivery to kidney. In this study, luciferase expressing human adipocyte derived stem cells (ADSC) were labelled with gold nanorods (GNR) and injected into the renal artery using ultrasound guidance. The ADSCs were tracked using bioluminescence and photoacoustic imaging serially over 7 days. Imaging confirmed that the majority of signal was within the kidney, indicative of successful injection and that the cells remained viable for 3 days. Histology showed co-localization of GNRs with ADSC staining throughout the kidney with no indication of injury caused by injection. These findings demonstrate that ultrasound-guided renal artery injection is feasible in mice and can successfully deliver a large proportion of cells which are retained within the kidney for 3 days. Therefore, the techniques developed here will be useful for optimising cell therapy in kidney diseases.

摘要

细胞疗法是治疗各种肾脏疾病的有前途的方法。然而,启动治疗反应的主要障碍是注射途径将细胞递送到肾脏实质的效率低下。全身注射,如静脉注射,只能将一小部分细胞递送到肾脏。而直接递送,如肾动脉注射需要手术。因此,开发了一种微创性肾动脉注射方法以增强细胞向肾脏的输送。在这项研究中,用金纳米棒(GNR)标记表达荧光素酶的人脂肪源性干细胞(ADSC),并使用超声引导将其注入肾动脉。使用生物发光和光声成像在 7 天内连续追踪 ADSC。成像证实,大多数信号位于肾脏内,表明注射成功,并且细胞在 3 天内保持活力。组织学显示 GNR 与 ADSC 染色在整个肾脏中均有共定位,没有表明注射引起的损伤。这些发现表明,超声引导的肾动脉注射在小鼠中是可行的,并且可以成功地将很大一部分细胞递送到肾脏内并保留 3 天。因此,这里开发的技术将有助于优化肾脏疾病的细胞治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afb6/7200714/4db59ab01a30/41598_2020_64417_Fig1_HTML.jpg

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