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非离子型碘化造影剂对人脂肪间充质干细胞的细胞毒性作用

Cytotoxic Effects of Nonionic Iodinated Contrast Agent on Human Adipose-Derived Mesenchymal Stem Cells.

作者信息

Wu Tao, Nie Hai, Dietz Allan B, Salek David R, Smith Jay, van Wijnen Andre J, Qu Wenchun

机构信息

Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN.

Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN.

出版信息

PM R. 2018 Jun 1. doi: 10.1016/j.pmrj.2018.05.022.

DOI:10.1016/j.pmrj.2018.05.022
PMID:29860023
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6358519/
Abstract

BACKGROUND

Transplantation of mesenchymal stem cells (MSCs) is a promising therapy for degenerative spine conditions. However, cell therapy for painful spine degeneration presently requires use of contrast agents during fluoroscopy-guided injections, and the effects of these agents on MSCs represents a gap in knowledge.

OBJECTIVE

To investigate the biological effects of contrast media (CM) that are coinjected with MSCs.

DESIGN

Prospective observational study.

SETTING

Academic medical center.

PARTICIPANTS

Patient-derived clinical-grade culture expanded MSCs.

INTERVENTIONS

Iohexol (Omnipaque300) was reduced to 12.5%, 25%, 50%, and 100% of the stock solution and incubated with MSCs for 30 minutes, 4 hours, and 48 hours. We also used complete media and 12.5%, 25%, 50%, 100% of phosphate-buffered saline as a control group.

MAIN OUTCOME MEASURES

We examined cytotoxicity of iohexol at different concentrations and exposure duration, as well as the potential for recovery over time. Cell counts, mitochondrial activity, and quantitative real time reverse-transcriptase polymerase chain reaction of related genes were analyzed immediately after exposure (day 0) and after 2 days of exposure (day 2).

RESULTS

Human MSCs exhibit a time- and concentration-dependent cytotoxic response to iodinated CM. A brief, 30-minute exposure did not affect MSCs function and viability. However, extended treatment with iohexol for 4 hours at 50% or higher concentration had a significant impact on both viability and gene expression in MSCs.

CONCLUSIONS

CM (Omnipaque300) is cytotoxic to MSCs in a time-and concentration-dependent manner. Hence, the concentration of CM that accompanies MSC injections should be carefully considered during MSC therapy for disk-degenerative diseases.

LEVEL OF EVIDENCE

To be determined.

摘要

背景

间充质干细胞(MSCs)移植是治疗退行性脊柱疾病的一种有前景的疗法。然而,目前用于疼痛性脊柱退变的细胞治疗在荧光透视引导注射过程中需要使用造影剂,而这些药物对间充质干细胞的影响尚不清楚。

目的

研究与间充质干细胞共同注射的造影剂(CM)的生物学效应。

设计

前瞻性观察研究。

单位

学术医学中心。

对象

患者来源的临床级培养扩增的间充质干细胞。

干预措施

将碘海醇(欧乃派克300)稀释至原液的12.5%、25%、50%和100%,并与间充质干细胞孵育30分钟、4小时和48小时。我们还使用完全培养基和12.5%、25%、50%、100%的磷酸盐缓冲盐水作为对照组。

主要观察指标

我们检测了不同浓度和暴露时间的碘海醇的细胞毒性,以及随时间恢复的可能性。在暴露后(第0天)和暴露2天后(第2天)立即分析细胞计数、线粒体活性和相关基因的定量实时逆转录聚合酶链反应。

结果

人骨髓间充质干细胞对碘化造影剂表现出时间和浓度依赖性的细胞毒性反应。短暂暴露30分钟不影响间充质干细胞的功能和活力。然而,在50%或更高浓度下用碘海醇延长处理4小时对间充质干细胞的活力和基因表达均有显著影响。

结论

造影剂(欧乃派克300)对间充质干细胞具有时间和浓度依赖性的细胞毒性。因此,在间充质干细胞治疗椎间盘退行性疾病时,应仔细考虑与间充质干细胞注射同时使用的造影剂浓度。

证据水平

待确定。

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