Engineered models for placental toxicology: Emerging approaches based on tissue decellularization

Parameshwar, Prabu Karthick; Sagrillo-Fagundes, Lucas; Portilho, Nathália Azevedo; Pastor, William A.; Vaillancourt, Cathy; Moraes, Christopher

doi:10.1016/j.reprotox.2022.07.003

Cited by 6 publications

(1 citation statement)

References 181 publications

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“…Trophoblast fusion is hence critical for a successful pregnancy as the syncytiotrophoblast regulates transport between mother and fetus, and dysregulated fusion is associated with abnormal placentation that can lead to significant obstetric complications such as preeclampsia and intrauterine growth restrictions 5 . While several models exist with which to study placental transport 6,7 including recent advanced 'on-a-chip' devices [8][9][10][11][12][13] , creating perfectly fused syncytial sheets remains challenging in culture. While novel pluripotent stem cell models do provide one avenue to enhance fusion efficiencies [14][15][16] , developing a better understanding of the fundamental factors influencing syncytialization could further improve upon these advanced models, and enhance our understanding of the factors driving disease progression during pregnancy.…”

Section: Introductionmentioning

confidence: 99%

Directed biomechanical compressive forces enhance fusion efficiency in model placental trophoblast cultures

Parameshwar,

Li,

Arnauts

et al. 2024

Preprint

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The syncytiotrophoblast is a multinucleated structure that arises from fusion of mononucleated cytotrophoblasts, to sheath the placental villi and regulate transport across the maternal-fetal interface. Here, we ask whether the dynamic mechanical forces that must arise during villous development might influence fusion, and explore this question using in vitro choriocarcinoma trophoblast models. We demonstrate that mechanical stress patterns arise around sites of localized fusion in cell monolayers, in patterns that match computational predictions of villous morphogenesis. We then externally apply these mechanical stress patterns to cell monolayers and demonstrate that equibiaxial compressive stresses (but not uniaxial or equibiaxial tensile stresses) enhance expression of the syndecan-1 marker of fusion. These findings suggest that the mechanical stresses that contribute towards sculpting the placental villi may also impact fusion in the developing tissue. We then extend this concept towards 3D cultures and demonstrate that fusion can be enhanced by applying low isometric compressive stresses to spheroid models, even in the absence of an inducing agent. These results indicate that mechanical stimulation is a potent activator of cellular fusion, suggesting novel avenues to improve experimental reproductive modelling, placental tissue engineering, and understanding disorders of pregnancy development.

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