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急性缺血性肾损伤大鼠肾脏中经动脉注射的氧化铁标记间充质干细胞的体内磁共振成像:3T 下的检测与监测

In vivo magnetic resonance imaging of iron oxide-labeled, arterially-injected mesenchymal stem cells in kidneys of rats with acute ischemic kidney injury: detection and monitoring at 3T.

作者信息

Ittrich Harald, Lange Claudia, Tögel Florian, Zander Axel R, Dahnke Hannes, Westenfelder Christof, Adam Gerhard, Nolte-Ernsting Claus

机构信息

Department of Diagnostic and Interventional Radiology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, DE-20246 Hamburg, Germany.

出版信息

J Magn Reson Imaging. 2007 Jun;25(6):1179-91. doi: 10.1002/jmri.20925.

Abstract

PURPOSE

To evaluate MRI for a qualitative and quantitative in vivo tracking of intraaortal injected iron oxide-labeled mesenchymal stem cells (MSC) into rats with acute kidney injury (AKI).

MATERIALS AND METHODS

In vitro MRI and R2* measurement of nonlabeled and superparamagnetic iron oxide (SPIO)-labeled MSC (MSC(SPIO)) was performed in correlation to cellular iron content and cytological examination (Prussian blue, electron microscopy). In vivo MRI and R2* evaluation were performed before and after ischemic/reperfusion AKI (N = 14) and intraaortal injection of 1.5 x 10(6) MSC(SPIO) (N = 7), fetal calf serum (FCS) (medium, N = 6), and SPIO alone (N = 1) up to 14 days using a clinical 3T scanner. Signal to noise ratios (SNR), R2* of kidneys, liver, spleen, and bone marrow, renal function (creatinine [CREA], blood urea nitrogen [BUN]), and kidney volume were measured and tested for statistical significance (Student's t-test, P < 0.05) in comparison histology (hematoxylin and eosin [H&E], Prussian blue, periodic acid-Schiff [PAS], CD68).

RESULTS

In vitro, MSC(SPIO) showed a reduction of SNR and T2* with R2* approximately number of MSC(SPIO) (R2 = 0.98). In vivo MSC(SPIO) administration resulted in a SNR decrease (35 +/- 15%) and R2* increase (101 +/- 18.3%) in renal cortex caused by MSC(SPIO) accumulation in contrast to control animals (P < 0.01). Liver, spleen, and bone marrow (MSC(SPIO)) showed a delayed SNR decline/R2* increase (P < 0.05) resulting from MSC(SPIO) migration. The increase of kidney volume and the decrease in renal function (P < 0.05) was reduced in MSC-treated animals.

CONCLUSION

Qualitative and quantitative in vivo cell-tracking and monitoring of organ distribution of intraaortal injected MSC(SPIO) in AKI is feasible in MRI at 3T.

摘要

目的

评估磁共振成像(MRI)用于定性和定量体内追踪经主动脉注射的氧化铁标记间充质干细胞(MSC)在急性肾损伤(AKI)大鼠体内的情况。

材料与方法

对未标记和超顺磁性氧化铁(SPIO)标记的MSC(MSC(SPIO))进行体外MRI和R2测量,并与细胞铁含量和细胞学检查(普鲁士蓝、电子显微镜)相关联。在缺血/再灌注AKI前后(N = 14)以及经主动脉注射1.5×10(6) MSC(SPIO)(N = 7)、胎牛血清(FCS)(培养基,N = 6)和单独的SPIO(N = 1)后,使用临床3T扫描仪进行长达14天的体内MRI和R2评估。测量肾脏、肝脏、脾脏和骨髓的信噪比(SNR)、R2*、肾功能(肌酐[CREA]、血尿素氮[BUN])和肾脏体积,并与组织学(苏木精和伊红[H&E]、普鲁士蓝、过碘酸希夫[PAS]、CD68)进行比较,检验统计学意义(学生t检验,P < 0.05)。

结果

体外,MSC(SPIO)的SNR和T2降低,R2与MSC(SPIO)数量大致相关(R2 = 0.98)。体内给予MSC(SPIO)导致肾皮质的SNR降低(35±15%)和R2增加(101±18.3%),这是由于MSC(SPIO)在肾皮质积聚,与对照动物相比(P < 0.01)。肝脏、脾脏和骨髓(MSC(SPIO))显示出由于MSC(SPIO)迁移导致的SNR延迟下降/R2增加(P < 0.05)。MSC治疗的动物肾脏体积增加和肾功能下降(P < 0.05)的情况有所减轻。

结论

在3T MRI中,对AKI大鼠经主动脉注射的MSC(SPIO)进行定性和定量体内细胞追踪以及监测其器官分布是可行的。

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