Effects of Pregnancy-Specific Glycoproteins on Trophoblast Motility in Three-Dimensional Gelatin Hydrogels.

IF 2.3 4区医学 Q3 BIOPHYSICS Cellular and molecular bioengineering Pub Date : 2022-04-01 DOI:10.1007/s12195-021-00715-7

Samantha G Zambuto, Shemona Rattila, Gabriela Dveksler, Brendan A C Harley

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引用次数: 2

Abstract

Introduction: Trophoblast invasion is a complex biological process necessary for establishment of pregnancy; however, much remains unknown regarding what signaling factors coordinate the extent of invasion. Pregnancy-specific glycoproteins (PSGs) are some of the most abundant circulating trophoblastic proteins in maternal blood during human pregnancy, with maternal serum concentrations rising to as high as 200-400 μg/mL at term.

Methods: Here, we employ three-dimensional (3D) trophoblast motility assays consisting of trophoblast spheroids encapsulated in 3D gelatin hydrogels to quantify trophoblast outgrowth area, viability, and cytotoxicity in the presence of PSG1 and PSG9 as well as epidermal growth factor and Nodal.

Results: We show PSG9 reduces trophoblast motility whereas PSG1 increases motility. Further, we assess bulk nascent protein production by encapsulated spheroids to highlight the potential of this approach to assess trophoblast response (motility, remodeling) to soluble factors and extracellular matrix cues.

Conclusions: Such models provide an important platform to develop a deeper understanding of early pregnancy.

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妊娠特异性糖蛋白对三维明胶水凝胶中滋养细胞运动的影响。

滋养细胞侵袭是一个复杂的生物学过程，是建立妊娠所必需的;然而，关于是什么信号因素协调了入侵的程度，仍然未知。妊娠特异性糖蛋白(PSGs)是人类妊娠期间母体血液中最丰富的循环滋养细胞蛋白之一，足月时母体血清浓度可高达200-400 μg/mL。方法:在这里，我们采用三维(3D)滋养细胞运动测定，由三维明胶水凝胶包裹的滋养细胞球体组成，量化滋养细胞在PSG1和PSG9以及表皮生长因子和Nodal存在下的生长面积、活力和细胞毒性。结果:我们发现PSG9降低了滋养细胞的运动性，而PSG1增加了滋养细胞的运动性。此外，我们评估了被封装的球体产生的大量新生蛋白，以强调这种方法在评估滋养细胞对可溶性因子和细胞外基质的反应(运动、重塑)方面的潜力。结论:该模型为深入了解早期妊娠提供了重要平台。

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来源期刊

Cellular and molecular bioengineering 生物-生物物理

CiteScore

5.60

自引率

3.60%

发文量

审稿时长

>12 weeks

期刊介绍： The field of cellular and molecular bioengineering seeks to understand, so that we may ultimately control, the mechanical, chemical, and electrical processes of the cell. A key challenge in improving human health is to understand how cellular behavior arises from molecular-level interactions. CMBE, an official journal of the Biomedical Engineering Society, publishes original research and review papers in the following seven general areas: Molecular: DNA-protein/RNA-protein interactions, protein folding and function, protein-protein and receptor-ligand interactions, lipids, polysaccharides, molecular motors, and the biophysics of macromolecules that function as therapeutics or engineered matrices, for example. Cellular: Studies of how cells sense physicochemical events surrounding and within cells, and how cells transduce these events into biological responses. Specific cell processes of interest include cell growth, differentiation, migration, signal transduction, protein secretion and transport, gene expression and regulation, and cell-matrix interactions. Mechanobiology: The mechanical properties of cells and biomolecules, cellular/molecular force generation and adhesion, the response of cells to their mechanical microenvironment, and mechanotransduction in response to various physical forces such as fluid shear stress. Nanomedicine: The engineering of nanoparticles for advanced drug delivery and molecular imaging applications, with particular focus on the interaction of such particles with living cells. Also, the application of nanostructured materials to control the behavior of cells and biomolecules.