Department of Biological Sciences, Oakland University, Rochester, MI 48309, USA; OU-WB Institute for Stem Cell and Regenerative Medicine, Oakland University, Rochester, MI 48309, USA.
Beaumont Health System, Royal Oak, MI 48073, USA.
Toxicol Appl Pharmacol. 2018 Jun 15;349:72-82. doi: 10.1016/j.taap.2018.04.032. Epub 2018 Apr 26.
Radiocontrast dyes are used for a wide range of diagnostic procedures for enhancing the image of anatomical structures, pain targets, and vascular uptake. While some of these dyes show toxicity to primary cells, their effect on stem cells, particularly mesenchymal stem cells (MSCs), is unknown. This study investigates the cytotoxic effects of two clinically used radiocontrast dyes, iohexol and iopamidol, on bone marrow and human umbilical cord MSCs. Exposure to these dyes significantly affected morphology of MSCs from both sources, as treated cells appeared transparent and no longer fibroblastoid. Cell viability decreased as determined by trypan blue and Annexin-V/PI staining, in a dose dependent manner with simultaneous loss of CD90 and CD105 concurrent with spontaneous differentiation in MSCs treated with iohexol and iopamidol. In addition, significantly higher cell death was observed in MSCs exposed to iopamidol than iohexol. At a concentration of 1:1, iohexol and iopamidol induced apoptosis in 19% and 92% (<.01) of MSCs, respectively. Global transcriptome analysis of treated MSCs revealed 139 and 384 differentially expressed genes in iohexol vs control and iopamidol vs control at p ≤ .01 and 1.5-fold, respectively. This suggested that iopamidol had more significant effect on the transcription of MSCs. Based on these results a molecular mechanism of radiocontast dye induced cell death via intrinsic apoptosis pathway mediated by p53 was proposed. Since iopamidol was significantly more toxic than iohexol in human MSCs, a more careful examination of safety of radiocontrast dyes for clinical use is warranted.
放射性对比染料被广泛用于增强解剖结构、疼痛靶点和血管摄取的影像的诊断程序。虽然这些染料中的一些对原代细胞有毒性，但它们对干细胞的影响，特别是间充质干细胞（MSCs）的影响尚不清楚。本研究调查了两种临床使用的放射性对比染料，碘海醇和碘帕醇，对骨髓和人脐带 MSCs 的细胞毒性作用。暴露于这些染料显著影响了两种来源的 MSCs 的形态，因为处理后的细胞呈现透明状，不再呈现成纤维细胞样。通过台盼蓝和 Annexin-V/PI 染色测定细胞活力，发现细胞活力呈剂量依赖性下降，同时伴随着 CD90 和 CD105 的丧失，以及碘海醇和碘帕醇处理的 MSCs 自发分化。此外，与碘海醇相比，暴露于碘帕醇的 MSCs 观察到更高的细胞死亡。在浓度为 1:1 时，碘海醇和碘帕醇分别诱导 19%和 92%（<0.01）的 MSCs 发生凋亡。用碘海醇和碘帕醇处理的 MSCs 的全转录组分析显示，与对照相比，在 p 值≤0.01 时，碘海醇组有 139 个和 384 个差异表达基因，而碘帕醇组有 1.5 倍的差异表达基因。这表明碘帕醇对 MSCs 的转录有更显著的影响。基于这些结果，提出了一种放射性对比染料通过 p53 介导的内在凋亡途径诱导细胞死亡的分子机制。由于碘帕醇在人 MSCs 中的毒性明显大于碘海醇，因此需要更仔细地检查放射性对比染料在临床使用中的安全性。
