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

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, Kristine C. McGrath, Louise Cole, Philip M. Hansbro and Lana McClements ()
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Claire Richards: 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
Catherine A. Gorrie: University of Technology Sydney
David Gallego-Ortega: University of Technology 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

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: 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.

Date: 2025
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62996-0

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DOI: 10.1038/s41467-025-62996-0

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