Matrix directs trophoblast differentiation in a bioprinted organoid model of early placental development
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.
Authors
- Matthew B. O’Rourke (ORCID: https://orcid.org/0000-0002-0552-2962)
- Lana McClements (ORCID: https://orcid.org/0000-0002-4911-1014)
- David Gallego‐Ortega (ORCID: https://orcid.org/0000-0002-2347-7835)
- Matthew Paul Padula (ORCID: https://orcid.org/0000-0002-8283-0643)
- Claire Richards (ORCID: https://orcid.org/0000-0001-5080-9164)
- Grace Owen
- Louise Cole (ORCID: https://orcid.org/0000-0001-9206-9272)
- Andrew J. Bannister (ORCID: https://orcid.org/0000-0002-6312-4436)
- Amy L. Bottomley (ORCID: https://orcid.org/0000-0003-0255-0869)
- Catherine A. Gorrie (ORCID: https://orcid.org/0000-0001-5934-2492)
- Philip M. Hansbro (ORCID: https://orcid.org/0000-0002-4741-3035)
- Alexander Volkerling
- Kristine McGrath (ORCID: https://orcid.org/0000-0002-6244-3929)
- Hao Chen (ORCID: https://orcid.org/0000-0003-0233-340X)
- Arnab Ghosh (ORCID: https://orcid.org/0009-0003-2581-3585)
Institutions
- University of Technology Sydney (AU)
- The University of Sydney (AU)
- Garvan Institute of Medical Research (AU)
- Centenary Institute (AU)
- UNSW Sydney (AU)
- Hunter Medical Research Institute (AU)
- National Imaging Facility (AU)
- The Kinghorn Cancer Centre (AU)
- University of Newcastle Australia (AU)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-09-12
- DOI
- https://doi.org/10.1038/s41467-025-62996-0
- Citations
- 4
- Primary Topic
- Pregnancy and preeclampsia studies
- Type
- article
- Field-Weighted Citation Impact
- 8.23