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毒性对人类脂肪间充质干细胞/基质细胞的影响,这些细胞急性暴露于多氯联苯的 Aroclor 和非 Aroclor 混合物中。

Toxicity Impacts on Human Adipose Mesenchymal Stem/Stromal Cells Acutely Exposed to Aroclor and Non-Aroclor Mixtures of Polychlorinated Biphenyl.

机构信息

Roy J. Carver Department of Biomedical Engineering, University of Iowa, Iowa City, Iowa 52242, United States.

Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, Iowa 52242, United States.

出版信息

Environ Sci Technol. 2023 Jan 31;57(4):1731-1742. doi: 10.1021/acs.est.2c07281. Epub 2023 Jan 18.

Abstract

Polychlorinated biphenyl (PCB) accumulates in adipose where it may impact the growth and function of cells within the tissue. This is particularly concerning during adolescence when adipocytes expand rapidly. Herein, we sought to understand how exposure to PCB mixtures found in U.S. schools affects human adipose mesenchymal stem/stromal cell (MSC) health and function. We investigated how exposure to Aroclor 1016 and Aroclor 1254, as well as a newly characterized non-Aroclor mixture that resembles the PCB profile found in cabinets, Cabinet Mixture, affects adipose MSC growth, viability, and function in vitro. We found that exposure to all three mixtures resulted in two distinct types of toxicity. At PCB concentrations >20 μM, the majority of MSCs die, while at 1-10 μM, MSCs remained viable but display numerous alterations to their phenotype. At these sublethal concentrations, the MSC rate of expansion slowed and morphology changed. Further assessment revealed that PCB-exposed MSCs had impaired adipogenesis and a modest decrease in immunosuppressive capabilities. Thus, exposure to PCB mixtures found in schools negatively impacts the health and function of adipose MSCs. This work has implications for human health due to MSCs' role in supporting the growth and maintenance of adipose tissue.

摘要

多氯联苯(PCB)在脂肪中积累,可能会影响组织内细胞的生长和功能。这在青少年时期尤为令人担忧,因为此时脂肪细胞迅速扩张。在此,我们试图了解在美国学校中发现的 PCB 混合物暴露如何影响人类脂肪间充质干细胞/基质细胞(MSC)的健康和功能。我们研究了暴露于 Aroclor 1016 和 Aroclor 1254 以及一种新表征的非 Aroclor 混合物(类似于柜橱中发现的 PCB 分布,称为 Cabinet Mixture)如何影响脂肪 MSC 的体外生长、活力和功能。我们发现,所有三种混合物的暴露都会导致两种不同类型的毒性。在 PCB 浓度>20 μM 时,大多数 MSC 死亡,而在 1-10 μM 时,MSC 仍保持活力,但表型发生了许多改变。在这些亚致死浓度下,MSC 的扩增速度减慢,形态发生变化。进一步评估显示,暴露于 PCB 的 MSC 的脂肪生成能力受损,免疫抑制能力略有下降。因此,学校中发现的 PCB 混合物的暴露会对脂肪 MSC 的健康和功能产生负面影响。由于 MSC 在支持脂肪组织的生长和维持方面的作用,这项工作对人类健康具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea23/9893815/502d48423c28/es2c07281_0002.jpg

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