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Stem Cell Reports. 2018 Aug 14;11(2):537-551. doi: 10.1016/j.stemcr.2018.07.004. Epub 2018 Aug 2.

Self-Renewing Trophoblast Organoids Recapitulate the Developmental Program of the Early Human Placenta.

Author information

1
Department of Obstetrics and Gynaecology, Medical University of Vienna, Reproductive Biology Unit, Währinger Gürtel 18-20, 5Q, 1090 Vienna, Austria.
2
Center for Anatomy and Cell Biology, Medical University of Vienna, Schwarzspanierstrasse 17, 1090 Vienna, Austria.
3
Institute of Molecular Biotechnology, Austrian Academy of Sciences, 1030 Vienna, Austria.
4
Gynmed Clinic, 1150 Vienna, Austria.
5
Center for Anatomy and Cell Biology, Medical University of Vienna, Schwarzspanierstrasse 17, 1090 Vienna, Austria. Electronic address: paulina.latos@meduniwien.ac.at.
6
Department of Obstetrics and Gynaecology, Medical University of Vienna, Reproductive Biology Unit, Währinger Gürtel 18-20, 5Q, 1090 Vienna, Austria. Electronic address: martin.knoefler@meduniwien.ac.at.

Abstract

Defective placentation is the underlying cause of various pregnancy complications, such as severe intrauterine growth restriction and preeclampsia. However, studies on human placental development are hampered by the lack of a self-renewing in vitro model that would recapitulate formation of trophoblast progenitors and differentiated subtypes, syncytiotrophoblast (STB) and invasive extravillous trophoblast (EVT), in a 3D orientation. Hence, we established long-term expanding organoid cultures from purified first-trimester cytotrophoblasts (CTBs). Molecular analyses revealed that the CTB organoid cultures (CTB-ORGs) express markers of trophoblast stemness and proliferation and are highly similar to primary CTBs at the level of global gene expression. Whereas CTB-ORGs spontaneously generated STBs, withdrawal of factors for self-renewal induced trophoblast outgrowth, expressing the EVT progenitor marker NOTCH1, and provoked formation of adjacent, distally located HLA-G+ EVTs. In summary, we established human CTB-ORGs that grow and differentiate under defined culture conditions, allowing future human placental disease modeling.

KEYWORDS:

Wnt signalling; cell fusion; cytotrophoblast organoids; differentiation; extravillous trophoblast lineage; human placenta; self-renewal

PMID:
30078556
PMCID:
PMC6092984
DOI:
10.1016/j.stemcr.2018.07.004
[Indexed for MEDLINE]
Free PMC Article

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