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胎儿膜器官芯片:研究细胞相互作用的创新方法。

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

机构信息

Division of Maternal-Fetal Medicine and Perinatal Research, Department of Obstetrics and Gynecology, The University of Texas Medical Branch, 301 University Blvd, Galveston, TX, 77555, USA.

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

出版信息

Reprod Sci. 2020 Aug;27(8):1562-1569. doi: 10.1007/s43032-020-00184-9.

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

胎膜是维持妊娠和促进分娩信号的重要组成部分,由于其结构复杂,通常分段研究。Transwell 传统上用于研究细胞相互作用,但它们的用途有限。为了克服这些困难,创建了胎儿膜器官芯片(FM-OO-C),以研究与 Transwell 系统相比,羊膜上皮细胞(AEC)和蜕膜细胞的相互作用特性。

方法

从足月、非分娩的胎膜中培养原代 AEC 和蜕膜细胞,将其置于 2 室(AEC/蜕膜细胞)FM-OO-C 装置中,并夹在半透膜之间。用香烟烟雾提取物(CSE)或二恶英处理细胞,并在 48 小时后测量膜通透性和细胞衰老。在 Transwell 中进行相同的实验进行比较。

结果

与 Transwell 培养相比,FM-OO-C 模型产生的膜通透性读数更好,无论处理侧还是时间点如何。直接用 CSE 处理的 AEC 的膜通透性增加(1.6 倍),而在蜕膜侧类似处理的膜通透性增加(1.2 倍)。在 FM-OO-C 中,处理迫使细胞层之间发生变化。当 CSE 和二恶英诱导的一侧室的衰老产生对面相同的变化时,这种效应就很明显。这种效应在 Transwell 系统中最小。

结论

FM-OO-C 的受控环境通过最小化噪声并突出处理之间无法在传统 Transwell 设备中看到的微小变化,允许细胞之间更好的信号传递。胎儿膜器官芯片提供了更好的细胞类型之间的相互作用,可以在未来的研究中用于研究妊娠期间的胎儿-母体信号。

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