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胎膜芯片:一种研究细胞间相互作用的创新方法。

Fetal Membrane Organ-On-Chip: An Innovative Approach to Study Cellular Interactions.

作者信息

Richardson Lauren, Gnecco Juan, Ding Tianbing, Osteen Kevin, Rogers Lisa M, Aronoff David M, Menon Ramkumar

机构信息

1 Division of Maternal-Fetal Medicine & Perinatal Research, Department of Obstetrics & Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX, USA.

2 Department of Neuroscience, Cell Biology & Anatomy, The University of Texas Medical Branch at Galveston, Galveston, TX, USA.

出版信息

Reprod Sci. 2019 Feb 21:1933719119828084. doi: 10.1177/1933719119828084.

DOI:10.1177/1933719119828084
PMID:30791822
Abstract

OBJECTIVE

: Fetal membranes, a vital component that helps maintain pregnancy and contribute to parturition signaling, are often studied in segments due to its structural complexity. Transwells are traditionally used to study cell interactions; however, their usefulness is limited. To overcome these difficulties, a fetal membrane-organ-on-chip (FM-OO-C) was created to study interactive properties of amnion epithelial cells (AECs) and decidual cells compared to transwell systems.

METHODS

: Primary AECs and decidual cells from term, nonlaboring fetal membranes were cultured in a 2-chamber (AEC/decidual cell) FM-OO-C device and sandwiched between a semipermeable membrane. Cells were treated with cigarette smoke extract (CSE) or dioxin, and membrane permeability and cellular senescence were measured after 48 hours. The same experiments were conducted in transwells for comparisons.

RESULTS

: Compared to transwell cultures, FM-OO-C model produced better membrane permeability readings regardless of the side of treatment or time point. Membrane permeabilization was higher in AECs directly treated with CSE (1.6 fold) compared to similar treatment on the decidual side (1.2 fold). In FM-OO-C, treatments forced changes between cellular layers. This was evident when CSE and dioxin-induced senescence on one side of the chamber produced similar changes on the opposite side. This effect was minimal in the transwell system.

CONCLUSION

: The controlled environment of an FM-OO-C allows for improved signal propagation between cells by minimizing noise and highlighting the small changes between treatments that cannot be seen in conventional transwell devices. Fetal membrane-organ-on-chip provides a better interaction between cell types that can be used to study fetal-maternal signaling during pregnancy in future studies.

摘要

目的

胎膜是有助于维持妊娠并参与分娩信号传导的重要组成部分,由于其结构复杂,通常分段进行研究。传统上使用Transwell来研究细胞间相互作用;然而,其用途有限。为克服这些困难,创建了一种胎膜芯片器官(FM-OO-C),以研究羊膜上皮细胞(AEC)和蜕膜细胞的相互作用特性,并与Transwell系统进行比较。

方法

将足月未临产胎膜的原代AEC和蜕膜细胞培养在一个双室(AEC/蜕膜细胞)FM-OO-C装置中,夹在半透膜之间。用香烟烟雾提取物(CSE)或二噁英处理细胞,48小时后测量膜通透性和细胞衰老情况。在Transwell中进行相同实验以作比较。

结果

与Transwell培养相比,无论处理侧或时间点如何,FM-OO-C模型产生的膜通透性读数更好。直接用CSE处理的AEC中的膜通透性增加(1.6倍),高于蜕膜侧类似处理(1.2倍)。在FM-OO-C中,处理促使细胞层之间发生变化。当腔室一侧的CSE和二噁英诱导衰老在另一侧产生类似变化时,这一点很明显。在Transwell系统中这种效应最小。

结论

FM-OO-C的可控环境通过最小化噪声并突出传统Transwell装置中无法看到的处理之间的微小变化,改善了细胞间的信号传播。胎膜芯片器官在细胞类型之间提供了更好的相互作用,可用于未来研究妊娠期间的胎儿-母体信号传导。

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