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Rotating Cell Culture Systems for Human Cell Culture: Human Trophoblast Cells as a Model
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Organoids in modeling human trophoblast development.

Alexander G Beristain1, Gina L McNeill1

  • 1The British Columbia Children's Hospital Research Institute, Vancouver, British Columbia, Canada; Department of Obstetrics and Gynecology, The University of British Columbia, Vancouver, British Columbia, Canada.

Fertility and Sterility
|November 5, 2025
PubMed
Summary

Human trophoblast organoids offer a powerful new way to study early pregnancy development. These advanced models improve our understanding of placental formation and pregnancy complications.

Keywords:
Human placentaepithelial organoidtrophoblasttrophoblast organoidtrophoblast stem cell

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Area of Science:

  • Reproductive Biology
  • Stem Cell Science
  • Developmental Biology

Background:

  • Human trophoblast development is crucial for successful pregnancy but difficult to study due to limited tissue access and inadequate animal models.
  • Advances in stem cell and organoid technologies now provide more accurate models of human trophoblast biology.

Purpose of the Study:

  • To review the development and capabilities of human trophoblast organoids.
  • To outline their utility in studying trophoblast lineage specification.
  • To discuss their role in understanding placental development and pregnancy pathologies.

Main Methods:

  • Literature review of trophoblast model systems, organoid establishment, and stem cell cultures (2018-2025).
  • Benchmarking organoids against in vivo trophoblast populations using transcriptomic, epigenetic, and functional assays.
  • Focus on lineage fidelity, culture refinements, and infection modeling.

Main Results:

  • First-trimester trophoblast organoids model progenitor cells and lineage generation (syncytiotrophoblast, extravillous trophoblast).
  • Various organoid systems (term, pluripotent stem cell-derived) offer different strengths and limitations.
  • Organoids provide insights into viral infections, impaired invasion, epigenetic memory, and patient-specific placental dysfunction.

Conclusions:

  • Trophoblast organoids are advanced in vitro systems for studying human trophoblast development, bridging the gap between animal models and primary tissues.
  • They enable detailed analysis of lineage specification and patient-specific pathophysiology.
  • Organoids hold promise for fundamental discovery and translational applications in reproductive medicine, including potential clinical uses.