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表观扩散系数是监测脂肪间充质干细胞治疗肾缺血再灌注损伤的有用生物标志物。

Apparent Diffusion Coefficient is a Useful Biomarker for Monitoring Adipose-Derived Mesenchymal Stem Cell Therapy of Renal Ischemic-Reperfusion Injury.

机构信息

Department of Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta-Pei Road, Kaohsiung, Niao-Sung District, 833, Taiwan.

Department of Cardiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 833, Taiwan.

出版信息

Mol Imaging Biol. 2018 Oct;20(5):750-760. doi: 10.1007/s11307-018-1184-0.

Abstract

PURPOSE

This study aimed to investigate the potential of apparent diffusion coefficient (ADC) for monitoring adipose-derived mesenchymal stem cell (ADMSC) therapy of renal ischemic-reperfusion injury (IRI).

PROCEDURES

After baseline magnetic resonance imaging (MRI), 36 Sprague-Dawley rats with bilateral renal IRI were divided equally as groups 1, 2, and 3 (non-treated rats) and groups 4, 5, and 6 (ADMSC-treated rats, with 2 million ADMSCs injected via the tail vein at 6 h after IRI). Groups 1 and 4, 2 and 5, and 3 and 6 were euthanized at days 1, 3, and 7, respectively, after renal MRI. The ratios of ADC at different time points to baseline values in the cortex, outer, and inner stripes of outer medulla (OSOM/ISOM), assessments of monocyte chemoattractant protein-1 (MCP-1), CD68+ cells, tubular cast formation, and degree of fibrosis in three zones over time were compared between the non-treated and ADMSC-treated rats.

RESULTS

Among three zones, the differences in cortical ADC and immunohistochemical changes between the non-treated and ADMSC-treated IRI rats over time were less obvious. Compared with the non-treated rats, the ADMSC-treated rats exhibited significantly higher ADC ratios of OSOM and ISOM at days 1 and 3 corresponding to significantly less MCP-1 staining, CD68+ cells, and tubular casts. From day 3 to day 7, coupling with the decrement of MCP-1 and CD68+ cells in IRI kidneys, the effect of cell density on ADC declined. By day 7, the ADMSC-treated rats showed significantly higher ADC ratios of ISOM than the non-treated IRI rats, indicating better recovery, which could be related to significantly fewer tubular casts and marked amelioration of fibrosis.

CONCLUSIONS

We suggest ADC is a useful in vivo biomarker for monitoring ADMSC therapy of renal IRI.

摘要

目的

本研究旨在探讨表观扩散系数(ADC)在监测脂肪间充质干细胞(ADMSC)治疗肾缺血再灌注损伤(IRI)中的潜力。

方法

在基线磁共振成像(MRI)后,将 36 只双侧肾 IRI 的 Sprague-Dawley 大鼠等分为非治疗组(1、2 和 3 组)和 ADMSC 治疗组(4、5 和 6 组,在 IRI 后 6 小时通过尾静脉注射 200 万 ADMSC)。各组分别在肾 MRI 后第 1、3 和 7 天处死。比较非治疗组和 ADMSC 治疗组在不同时间点皮质、外带和外髓内层(OSOM/ISOM)的 ADC 比值与基线值的比值、单核细胞趋化蛋白-1(MCP-1)、CD68+细胞、肾小管铸型形成和纤维化程度的变化。

结果

在三个区域中,非治疗和 ADMSC 治疗 IRI 大鼠在皮质 ADC 和免疫组化变化方面随时间的差异不明显。与非治疗组相比,ADMSC 治疗组在第 1 和第 3 天 OSOM 和 ISOM 的 ADC 比值明显升高,MCP-1 染色、CD68+细胞和肾小管铸型明显减少。从第 3 天到第 7 天,随着 IRI 肾脏中 MCP-1 和 CD68+细胞的减少,细胞密度对 ADC 的影响下降。第 7 天,ADMSC 治疗组 ISOM 的 ADC 比值明显高于非治疗 IRI 组,表明恢复情况较好,这可能与肾小管铸型明显减少和纤维化明显改善有关。

结论

我们认为 ADC 是监测 ADMSC 治疗肾 IRI 的一种有用的体内生物标志物。

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