In vitro teratogenicity testing using a 3D, embryo-like gastruloid system

Mantziou, Veronika; Baillie-Benson, Peter; Jaklin, Manuela; Kustermann, Stefan; Arias, Alfonso Martínez; Moris, Naomi

doi:10.1016/j.reprotox.2021.08.003

Cited by 43 publications

(22 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Gastruloids have been recently proposed as cell-based models for drug safety testing ( Mantziou et al., 2021 ); our findings showing that a commonly used antiasthma drug inhibits gastruloid development, can open the way to further investigate unwanted effects of budesonide treatment on fertility in women. Indeed, partial infertility has been reported in asthmatic women ( Gade et al., 2014 ; Vejen Hansen et al., 2019 ), yet, to our knowledge, the effects of budesonide on pregnancy have not been directly investigated with well-controlled and adequate clinical trials ( Kalola and Ambati, 2021 ).…”

Section: Discussionmentioning

confidence: 71%

Stabilization of cell-cell adhesions prevents symmetry breaking and locks in pluripotency in 3D gastruloids

Cermola

Amoroso²,

Saracino³

et al. 2022

Stem Cell Reports

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 71%

Stabilization of cell-cell adhesions prevents symmetry breaking and locks in pluripotency in 3D gastruloids

Cermola

Amoroso²,

Saracino³

et al. 2022

Stem Cell Reports

View full text Add to dashboard Cite

“…Beyond genetic causes, congenital heart defects can also be caused by teratogens (e. g. drugs, toxins, metabolites) (Kalisch-Smith et al, 2019). However, no human system exists in which it is possible to investigate, in a high-throughput and easily quantifiable manner, whether teratogens cause compartment- specific defects (Mantziou et al, 2021). Before setting out to test the potential applicability of the cardioid compartment platform in this setting, we first confirmed that a non-teratogenic factor Aspirin (Mantziou et al, 2021; van Meer et al, 2019), at a high 30 μM dosage, did not cause any morphological or significant gene expression differences (Figures S7A, S7A’, and S7B), showing that the cardioid system is not overly sensitive to non-teratogenic drugs.…”

Section: Resultsmentioning

confidence: 99%

Multi-chamber cardioids unravel human heart development and cardiac defects

Schmidt

Deyett

Ilmer

et al. 2022

Preprint

View full text Add to dashboard Cite

The number one cause of human fetal death are defects in heart development. Because the human embryonic heart is inaccessible, and the impacts of mutations, drugs, and environmental factors on the specialized functions of different heart compartments are not captured by in vitro models, determining the underlying causes is difficult. Here, we established a human cardioid platform that recapitulates the development of all major embryonic heart compartments, including right and left ventricles, atria, outflow tract, and atrioventricular canal. By leveraging both 2D and 3D differentiation, we efficiently generated progenitor subsets with distinct first, anterior, and posterior second heart field identities. This advance enabled the reproducible generation of cardioids with compartment-specific in vivo-like gene expression profiles, morphologies, and functions. We used this platform to unravel the ontogeny of signal and contraction propagation between interacting heart chambers and dissect how genetic and environmental factors cause region-specific defects in the developing human heart.

show abstract

“…Human embryo models could also be used to screen for drug toxicity. In a proofof-concept study, Moris has shown that the drug thalidomide -infamous for causing birth defects in humans, but not particularly toxic in mice -had a stronger effect on human gastruloids than on mouse gastruloids, suggesting that these models could be useful for human-specific toxicological screens 15 .…”

Section: Varied Applicationsmentioning

confidence: 99%

Embryo-like models shed fresh light on early human development

Ravindran¹

2021

Nature

View full text Add to dashboard Cite

Cells in culture typically form continuous sheets, like skin. But in 2017, bioengineer Jianping Fu realized that if he cultured human stem cells in a 3D scaffold, they would spontaneously organize into structures that looked, under a microscope, a bit like an embryo 1 . Gene-expression analyses suggested the cells were similar to those in an embryo immediately after it implants in the uterus, meaning they could serve as experimental models for a previously opaque point in early development."Once the human embryo implants into the maternal uterus, it becomes invisible," says Fu, at the University of Michigan in Ann Arbor. "That time frame is really a black box." But it's crucially important. This stage, about 7 to 10 days after fertilization in humans, is marked by formation of the amniotic sac and the first signs of the primitive streak. That structure marks the point at which the embryo sets up the body axes and begins to distinguish head from tail and left from right.Researchers have long sought to observe and study these developmental stages. But working with human embryos has always been technically and ethically fraught. Animal models go only so far in mimicking humans. Natural human embryos, donated by people undergoing fertility treatment, are hard to come by. And until May this year, scientists were barred from culturing such embryos in the laboratory for longer than two weeks after fertilization. The International Society for Stem Cell Research (ISSCR) relaxed this 14-day rule in May, allowing research groups in countries where such work is legal to apply for permission to continue studies beyond 14 days.Given these limitations, it is no surprise that researchers have sought alternatives to natural human embryos in the lab. Stem cells from species such as mice have long provided a replacement -either embryonic stem cells (taken directly from early-stage embryos) or induced pluripotent stem cells CULTURE SYSTEMS MODEL EARLY HUMAN DEVELOPMENTStem-cell models offer a window into human and mouse embryogenesis. By Sandeep Ravindran Embryo models of the blastocyst stage of early development, reprogrammed from skin cells. MONASH UNIV.

show abstract

In vitro teratogenicity testing using a 3D, embryo-like gastruloid system

Cited by 43 publications

References 40 publications

Stabilization of cell-cell adhesions prevents symmetry breaking and locks in pluripotency in 3D gastruloids

Stabilization of cell-cell adhesions prevents symmetry breaking and locks in pluripotency in 3D gastruloids

Multi-chamber cardioids unravel human heart development and cardiac defects

Embryo-like models shed fresh light on early human development

Contact Info

Product

Resources

About