Molecular characteristics of established trophoblast-derived cell lines

Pastuschek, Jana; Nonn, Olivia; Gutiérrez-Samudio, Ruby N.; Murrieta-Coxca, José Martín; Müller, Jasmin; Sanft, Juliane; Huppertz, Berthold; Markert, Udo R.; Groten, T; Morales-Prieto, Diana M.

doi:10.1016/j.placenta.2021.02.022

Cited by 25 publications

(10 citation statements)

References 71 publications

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“…On the other hand, Park et al (2018) showed that the use of L-NAME (100 μM/mL) did not significantly alter the protein expression of the PGR-B in human placenta-derived cytotrophoblast-like BeWo cells treated for 24 h under hypoxic conditions in vitro [ 92 ]. Although our data align with the findings of Zhang et al (2018) regarding the lack of STAT3 activation in the L-NAME-treated placentae [ 91 ], it is likely that the cellular and molecular discrepancies between the HTR-8/SVneo cells and the BeWo cells particularly their downstream PGR-mediated responses [ 93 , 94 ], may have accounted for the differences in the L-NAME-mediated alterations in the PGR expression reported in the present study and that of Park et al (2018) [ 92 ].…”

Section: Discussionsupporting

confidence: 90%

Low-Dose Tacrolimus Promotes the Migration and Invasion and Nitric Oxide Production in the Human-Derived First Trimester Extravillous Trophoblast Cells In Vitro

Albaghdadi

Coyle

Kan

2022

IJMS

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Placentation is one of the most important determinants for a successful pregnancy, and this is dependent on the process of trophoblast migration and invasion. Progesterone receptors (PGR) are critical effectors of progesterone (P4) signaling that is required for trophoblast migration and invasion conducive to a successful gestation. In immune complicated pregnancies, evidence has shown that abnormal placentation occurs because of aberrant expression of PGR. Therapeutic intervention with tacrolimus (FK506) was able to restore PGR expression and improve pregnancy outcomes in immune-complicated gestations; however, the exact mode of action of tacrolimus in assisting placentation is not clear. Here, we attempt to uncover the mode of action of tacrolimus by examining its effects on trophoblast invasion and migration in the human-derived extravillous trophoblast (EVT) cell line, the HTR-8/SVneo cells. Using a variety of functional assays, we demonstrated that low-dose tacrolimus (10 ng/mL) was sufficient to significantly (p < 0.001) stimulate the migration and invasion of the HTR-8/SVneo cells, inducing their cytosolic/nuclear progesterone receptor expression and activation, and modulating their Nitric Oxide (NO) production. Moreover, tacrolimus abrogated the suppressive effect of the NOS inhibitor Nω- Nitro-L-Arginine Methyl Ester (L-NAME) on these vital processes critically involved in the establishment of human pregnancy. Collectively, our data suggest an immune-independent mode of action of tacrolimus in positively influencing placentation in complicated gestations, at least in part, through promoting the migration and invasion of the first trimester extravillous trophoblast cells by modulating their NO production and activating their cytosolic/nuclear progesterone-receptors. To our knowledge, this is the first report to show that the mode of action of tacrolimus as a monotherapy for implantation failure is plausibly PGR-dependent.

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Section: Discussionsupporting

confidence: 90%

Low-Dose Tacrolimus Promotes the Migration and Invasion and Nitric Oxide Production in the Human-Derived First Trimester Extravillous Trophoblast Cells In Vitro

Albaghdadi

Coyle

Kan

2022

IJMS

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“…Further studies are required to corroborate these findings. In addition, this work has several limitations, including the lack of a causative link between PE progression and defective cilia, small numbers of PE and control samples, term PE instead of early PE placenta-derived hCV-MSCs for functional analysis, and usage of the HTR cell line, which has been reported as a less valid cell model for human EVTs [ 82 ]. Finally, it is important to study the precise molecular mechanisms, how PE affects the formation and function of primary cilia on pMSCs, and how impaired pMSCs interact with and affect various placental cells in PE placentas.…”

Section: Discussionmentioning

confidence: 99%

Human placental mesenchymal stromal cells are ciliated and their ciliation is compromised in preeclampsia

Romberg

Kreis

Friemel

et al. 2022

BMC Med

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Background The development of the human placenta is tightly coordinated by a multitude of placental cell types, including human chorionic villi mesenchymal stromal cells (hCV-MSCs). Defective hCV-MSCs have been reported in preeclampsia (PE), a gestational hypertensive disease characterized by maternal endothelial dysfunction and systemic inflammation. Our goal was to determine whether hCV-MSCs are ciliated and whether altered ciliation is responsible for defective hCV-MSCs in preeclamptic placentas, as the primary cilium is a hub for signal transduction, which is important for various cellular activities. Methods In the present work, we collected placental tissues from different gestational stages and we isolated hCV-MSCs from 1st trimester, term control, and preeclamptic placentas. We studied their ciliation, functionality, and impact on trophoblastic cell lines and organoids formed from human trophoblast stem cells (hTSCs) and from the trophoblastic cell line JEG-3 with various cellular and molecular methods, including immunofluorescence staining, gene analysis, spheroid/organoid formation, motility, and cellular network formation assay. The statistical evaluation was performed using a Student’s t test (two-tailed and paired or homoscedastic) or an unpaired Mann–Whitney U test (two-tailed). Results The results show that primary cilia appeared abundantly in normal hCV-MSCs, especially in the early development of the placenta. Compared to control hCV-MSCs, the primary cilia were truncated, and there were fewer ciliated hCV-MSCs derived from preeclamptic placentas with impaired hedgehog signaling. Primary cilia are necessary for hCV-MSCs’ proper signal transduction, motility, homing, and differentiation, which are impaired in preeclamptic hCV-MSCs. Moreover, hCV-MSCs derived from preeclamptic placentas are significantly less capable of promoting growth and differentiation of placental organoids, as well as cellular network formation. Conclusions These data suggest that the primary cilium is required for the functionality of hCV-MSCs and primary cilia are impaired in hCV-MSCs from preeclamptic placentas.

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“…Diverse systems are available to decipher placental function and its impact on pregnancy pathologies [ 4 , 11 , 13 , 20 ]. In vitro culture of isolated primary cells, transfected primary cell lines, or choriocarcinoma cell lines represent useful and simple methods [ 21 ]; however, they do not reflect the in vivo micro-environment of cells in a tissue [ 11 ]. A prominent and well-established method to look at tissues in vitro is represented by placental dual lobe perfusion [ 22 ], which enables the analysis of diverse experimental hypotheses.…”

Section: Discussionmentioning

confidence: 99%

Placental Villous Explant Culture 2.0: Flow Culture Allows Studies Closer to the In Vivo Situation

Kupper

Pritz

Siwetz

et al. 2021

IJMS

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During pregnancy, freely floating placental villi are adapted to fluid shear stress due to placental perfusion with maternal plasma and blood. In vitro culture of placental villous explants is widely performed under static conditions, hoping the conditions may represent the in utero environment. However, static placental villous explant culture dramatically differs from the in vivo situation. Thus, we established a flow culture system for placental villous explants and compared commonly used static cultured tissue to flow cultured tissue using transmission and scanning electron microscopy, immunohistochemistry, and lactate dehydrogenase (LDH) and human chorionic gonadotropin (hCG) measurements. The data revealed a better structural and biochemical integrity of flow cultured tissue compared to static cultured tissue. Thus, this new flow system can be used to simulate the blood flow from the mother to the placenta and back in the most native-like in vitro system so far and thus can enable novel study designs.

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Molecular characteristics of established trophoblast-derived cell lines

Cited by 25 publications

References 71 publications

Low-Dose Tacrolimus Promotes the Migration and Invasion and Nitric Oxide Production in the Human-Derived First Trimester Extravillous Trophoblast Cells In Vitro

Low-Dose Tacrolimus Promotes the Migration and Invasion and Nitric Oxide Production in the Human-Derived First Trimester Extravillous Trophoblast Cells In Vitro

Human placental mesenchymal stromal cells are ciliated and their ciliation is compromised in preeclampsia

Placental Villous Explant Culture 2.0: Flow Culture Allows Studies Closer to the In Vivo Situation

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