Stem-cell-derived trophoblast organoids model human placental development and susceptibility to emerging pathogens

Karvas, Rowan M.; Khan, Shafqat Ali; Verma, Seema; Yin, Yan; Kulkarni, Devesha H.; Dong, Chen; Park, Kyoung Mi; Chew, Brian; Sane, Eshan; Fischer, Laura A.; Kumar, Deepak; Li, Ma; Boon, Adrianus C. M.; Dietmann, Sabine; Mysorekar, Indira U.; Theunissen, Thorold W.

doi:10.1016/j.stem.2022.04.004

Cited by 92 publications

(92 citation statements)

References 73 publications

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“…168 A robust cell line or organoid model may support precise understanding of SARS-CoV-2 pathogenesis during pregnancy. 169 From the above reports, it is evident that SARS-CoV-2 infections in the placenta could lead to adverse effects by impairing the essential physiological balance maintained through the RAS pathway. More in depth mechanistic studies are needed to understand the range of possible long term developmental defects on maternal and fetal health due to dysregulation of RAS pathways.…”

Section: Sars-cov-2 and Placental Immunitymentioning

confidence: 99%

COVID-19 and pregnancy: clinical outcomes; mechanisms, and vaccine efficacy

Kumar

Verma

Mysorekar

2023

Translational Research

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Section: Sars-cov-2 and Placental Immunitymentioning

confidence: 99%

COVID-19 and pregnancy: clinical outcomes; mechanisms, and vaccine efficacy

Kumar

Verma

Mysorekar

2023

Translational Research

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“…Previous work has shown that isolation and propagation of trophoblast stem cells from first trimester placental chorionic villi lead to the development of three-dimensional organoids that differentiate to contain all lineages of trophoblast cells present in the human placenta and release well-known pregnancy hormones such as human chorionic gonadotropin (hCG) ( Turco et al, 2018 ). Two-dimensional and organoid-based models of first trimester stem cells derived from villous tissue have also been reported and recapitulate key aspects of trophoblast biology ( Karvas et al, 2022 ; Okae et al, 2018 ; Shannon et al, 2017 ; Sheridan et al, 2021 ). Similarly, DOs isolated from uterine glands recapitulate the transcriptional profile of their tissue of origin and respond to hormonal cues ( Turco et al, 2017a ).…”

Section: Introductionmentioning

confidence: 97%

Innate immune signaling in trophoblast and decidua organoids defines differential antiviral defenses at the maternal-fetal interface

Yang

Semmes

Ovies

et al. 2022

eLife

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Infections at the maternal-fetal interface can directly harm the fetus and induce complications that adversely impact pregnancy outcomes. Innate immune signaling by both fetal-derived placental trophoblasts and the maternal decidua must provide antimicrobial defenses at this critical interface without compromising its integrity. Here, we developed matched trophoblast and decidua organoids from human placentas to define the relative contributions of these cells to antiviral defenses at the maternal-fetal interface. We demonstrate that trophoblast and decidua organoids basally secrete distinct immunomodulatory factors, including the constitutive release of the antiviral type III interferon IFN-λ2 from trophoblast organoids, and differentially respond to viral infections through the induction of organoid-specific factors. Lastly, we define the differential susceptibility and innate immune signaling of trophoblast and decidua organoids to human cytomegalovirus (HCMV) and develop a co-culture model of trophoblast and decidua organoids which showed that trophoblast-derived factors protect decidual cells from HCMV infection. Our findings establish matched trophoblast and decidua organoids as ex vivo models to study vertically transmitted infections and highlight differences in innate immune signaling by fetal-derived trophoblasts and the maternal decidua.

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“…To fill this gap, a number of human stem cell-based embryo models have been developed to recapitulate specific stages of human embryogenesis (Fan et al, 2021;Kagawa et al, 2021;Liu et al, 2021;Moris et al, 2020;Shao et al, 2017;Simunovic et al, 2022;Sozen et al, 2021;Veenvliet et al, 2020;Yanagida et al, 2021;Yu et al, 2021;Zhao et al, 2021). Naive human pluripotent stem cells (hPSCs) represent the preimplantation naive pluripotent epiblast and have the ability to differentiate into embryonic lineages as well as extraembryonic PrE and TB lineages, including human trophoblast stem cells (hTSCs) and amnion (Castel et al, 2020;Cinkornpumin et al, 2020;Dong et al, 2020;Guo et al, 2021;Io et al, 2021;Karvas et al, 2022;Linneberg-Agerholm et al, 2019;Rostovskaya et al, 2022). However, whether naive hPSCs have the ability to form additional extraembryonic lineages such as the EXM is unknown.…”

Section: Introductionmentioning

confidence: 99%