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Matrix directs trophoblast differentiation in a bioprinted organoid model of early placental development

Author

Listed:
  • Claire Richards

    (University of Technology Sydney
    University of Technology Sydney)

  • Hao Chen

    (School of Life Sciences)

  • Matthew O’Rourke

    (School of Life Sciences)

  • Ashley Bannister

    (University of Technology Sydney)

  • Grace Owen

    (University of Technology Sydney)

  • Alexander Volkerling

    (Inventia Life Science Pty Ltd)

  • Arnab Ghosh

    (University of Newcastle, Callaghan
    New Lambton Heights)

  • Catherine A. Gorrie

    (University of Technology Sydney)

  • David Gallego-Ortega

    (University of Technology Sydney
    The Kinghorn Cancer Centre
    University of New South Wales Sydney)

  • Amy L. Bottomley

    (University of Technology Sydney)

  • Matthew P. Padula

    (University of Technology Sydney)

  • Kristine C. McGrath

    (University of Technology Sydney)

  • Louise Cole

    (University of Technology Sydney)

  • Philip M. Hansbro

    (School of Life Sciences)

  • Lana McClements

    (University of Technology Sydney
    University of Technology Sydney)

Abstract

Trophoblast organoids can provide crucial insights into mechanisms of placentation, however their potential is limited by highly variable extracellular matrices unable to reflect in vivo tissues. Here, we present a bioprinted placental organoid model, generated using the first trimester trophoblast cell line, ACH-3P, and a synthetic polyethylene glycol (PEG) matrix. Bioprinted or Matrigel-embedded organoids differentiate spontaneously from cytotrophoblasts into two major subtypes: extravillous trophoblasts (EVTs) and syncytiotrophoblasts (STBs). Bioprinted organoids are driven towards EVT differentiation and show close similarity with early human placenta or primary trophoblast organoids. Inflammation inhibits proliferation and STBs within bioprinted organoids, which aspirin or metformin (0.5 mM) cannot rescue. We reverse the inside-out architecture of ACH-3P organoids by suspension culture with STBs forming on the outer layer of organoids, reflecting placental tissue. Our bioprinted methodology is applicable to trophoblast stem cells. We present a high-throughput, automated, and tuneable trophoblast organoid model that reproducibly mimics the placental microenvironment in health and disease.

Suggested Citation

  • Claire Richards & Hao Chen & Matthew O’Rourke & Ashley Bannister & Grace Owen & Alexander Volkerling & Arnab Ghosh & Catherine A. Gorrie & David Gallego-Ortega & Amy L. Bottomley & Matthew P. Padula &, 2025. "Matrix directs trophoblast differentiation in a bioprinted organoid model of early placental development," Nature Communications, Nature, vol. 16(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62996-0
    DOI: 10.1038/s41467-025-62996-0
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    References listed on IDEAS

    as
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    2. Margherita Y. Turco & Lucy Gardner & Richard G. Kay & Russell S. Hamilton & Malwina Prater & Michael S. Hollinshead & Alasdair McWhinnie & Laura Esposito & Ridma Fernando & Helen Skelton & Frank Reima, 2018. "Trophoblast organoids as a model for maternal–fetal interactions during human placentation," Nature, Nature, vol. 564(7735), pages 263-267, December.
    3. Jia Liu & Shengnan Hao & Xi Chen & Hui Zhao & Lutao Du & Hanxiao Ren & Chuanxin Wang & Haiting Mao, 2019. "Human placental trophoblast cells contribute to maternal–fetal tolerance through expressing IL-35 and mediating iTR35 conversion," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    4. Nikolce Gjorevski & Norman Sachs & Andrea Manfrin & Sonja Giger & Maiia E. Bragina & Paloma Ordóñez-Morán & Hans Clevers & Matthias P. Lutolf, 2016. "Designer matrices for intestinal stem cell and organoid culture," Nature, Nature, vol. 539(7630), pages 560-564, November.
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