TY - JOUR
KW - biomaterials
KW - Differentiation
KW - Tissue engineering
AU - Claire Richards
AU - Hao Chen
AU - Matthew O’Rourke
AU - Ashley Bannister
AU - Grace Owen
AU - Alexander Volkerling
AU - Arnab Ghosh
AU - Catherine A. Gorrie
AU - David Gallego-Ortega
AU - Amy L. Bottomley
AU - Matthew P. Padula
AU - Kristine C. McGrath
AU - Louise Cole
AU - Philip M. Hansbro
AU - Lana McClements
AB - 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.
BT - Nature Communications
DA - 2025-09-12
DO - 10.1038/s41467-025-62996-0
IS - 1
LA - en
N2 - 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.
PY - 2025
EP - 8267
T2 - Nature Communications
TI - Matrix directs trophoblast differentiation in a bioprinted organoid model of early placental development
UR - https://www.nature.com/articles/s41467-025-62996-0
VL - 16
Y2 - 2025-09-19
SN - 2041-1723
ER -