Trophoblast stem cell-based organoid models of the human placental barrier

Takeshi Hori, Hiroaki Okae, Shun Shibata, Norio Kobayashi, Eri H. Kobayashi, Akira Oike, Asato Sekiya, Takahiro Arima and Hirokazu Kaji ()
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Takeshi Hori: Tokyo Medical and Dental University (TMDU)
Hiroaki Okae: Tohoku University Graduate School of Medicine
Shun Shibata: Tohoku University Graduate School of Medicine
Norio Kobayashi: Tohoku University Graduate School of Medicine
Eri H. Kobayashi: Tohoku University Graduate School of Medicine
Akira Oike: Tohoku University Graduate School of Medicine
Asato Sekiya: Kumamoto University
Takahiro Arima: Tohoku University Graduate School of Medicine
Hirokazu Kaji: Tokyo Medical and Dental University (TMDU)

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: Abstract Human placental villi have essential roles in producing hormones, mediating nutrient and waste exchange, and protecting the fetus from exposure to xenobiotics. Human trophoblast organoids that recapitulate the structure of villi could provide an important in vitro tool to understand placental development and the transplacental passage of xenobiotics. However, such organoids do not currently exist. Here we describe the generation of trophoblast organoids using human trophoblast stem (TS) cells. Following treatment with three kinds of culture medium, TS cells form spherical organoids with a single outer layer of syncytiotrophoblast (ST) cells that display a barrier function. Furthermore, we develop a column-type ST barrier model based on the culture condition of the trophoblast organoids. The bottom membrane of the column is almost entirely covered with syndecan 1-positive ST cells. The barrier integrity and maturation levels of the model are confirmed by measuring transepithelial/transendothelial electrical resistance (TEER) and the amount of human chorionic gonadotropin. Further analysis reveals that the model can be used to derive the apparent permeability coefficients of model compounds. In addition to providing a suite of tools for the study of placental development, our trophoblast models allow the evaluation of compound transfer and toxicity, which will facilitate drug development.

Date: 2024
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DOI: 10.1038/s41467-024-45279-y

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