RRC ID 79146
著者 Hori T, Okae H, Shibata S, Kobayashi N, Kobayashi EH, Oike A, Sekiya A, Arima T, Kaji H.
タイトル Trophoblast stem cell-based organoid models of the human placental barrier.
ジャーナル Nat Commun
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.
巻・号 15(1)
ページ 962
公開日 2024-2-8
DOI 10.1038/s41467-024-45279-y
PII 10.1038/s41467-024-45279-y
PMID 38332125
PMC PMC10853531
MeSH Cell Differentiation Female Humans Organoids Placenta* Placentation Pregnancy Stem Cells Trophoblasts*
リソース情報
遺伝子材料 CS-CA-MCS (RDB05963) pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393)