Engineered trophoblast organoids recapitulate molecular and functional features of preeclampsia
- 1Flinders University
Abstract
Preeclampsia is a major pregnancy complication driven by placental dysfunction, yet research is limited by reliance on patient-derived tissues and models that do not fully capture human disease. Here, we develop a genetically engineered human trophoblast organoid model of preeclampsia that can be generated without access to placental tissue. Using a CRISPR-based Prime Integrase strategy, we engineered induced trophoblast stem cells to express the preeclampsia-associated soluble fms-like tyrosine kinase-1 (sFlt-1) exon 15a isoform. Engineered organoids showed a transcriptional shift towards primary preeclamptic placentae and developed several features of disease. These included reduced PlGF, increased IL-6 and soluble endoglin, oxidative stress, impaired growth and an elevated sFlt-1/PlGF ratio comparable to primary preeclamptic trophoblast organoids. These broader changes were not reproduced by adding recombinant human sFlt-1 to control organoids. Conditioned media from engineered organoids impaired endothelial network formation, demonstrating a functional effect of the altered trophoblast secretome. Treatment with sulfasalazine and metformin also restored angiogenic balance and organoid growth. Together, these findings establish a tractable human model that reproduces molecular and functional features of preeclampsia and provides a platform to study disease mechanisms and test potential therapies.
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BibTeX
@misc{arthurs2026engineered,
title = {{Engineered trophoblast organoids recapitulate molecular and functional features of preeclampsia}},
author = {A. L. Arthurs and C. Lushington and D. L. Medina Garcia and A. L. Merriman and G. A. Mora-Roldan and L. Parry and A. Boparai and J. M. Polo and F. L. Adikusuma and P. Q. Thomas and C. T. Roberts},
howpublished = {bioRxiv},
year = {2026},
month = jul,
doi = {10.64898/2026.07.22.739976},
url = {https://www.biorxiv.org/content/10.64898/2026.07.22.739976v2},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Engineered trophoblast organoids recapitulate molecular and functional features of preeclampsia
AU - A. L. Arthurs
AU - C. Lushington
AU - D. L. Medina Garcia
AU - A. L. Merriman
AU - G. A. Mora-Roldan
AU - L. Parry
AU - A. Boparai
AU - J. M. Polo
AU - F. L. Adikusuma
AU - P. Q. Thomas
AU - C. T. Roberts
PY - 2026
DA - 2026/07/22
PB - bioRxiv
DO - 10.64898/2026.07.22.739976
UR - https://www.biorxiv.org/content/10.64898/2026.07.22.739976v2
AB - Preeclampsia is a major pregnancy complication driven by placental dysfunction, yet research is limited by reliance on patient-derived tissues and models that do not fully capture human disease. Here, we develop a genetically engineered human trophoblast organoid model of preeclampsia that can be generated without access to placental tissue. Using a CRISPR-based Prime Integrase strategy, we engineered induced trophoblast stem cells to express the preeclampsia-associated soluble fms-like tyrosine kinase-1 (sFlt-1) exon 15a isoform. Engineered organoids showed a transcriptional shift towards primary preeclamptic placentae and developed several features of disease. These included reduced PlGF, increased IL-6 and soluble endoglin, oxidative stress, impaired growth and an elevated sFlt-1/PlGF ratio comparable to primary preeclamptic trophoblast organoids. These broader changes were not reproduced by adding recombinant human sFlt-1 to control organoids. Conditioned media from engineered organoids impaired endothelial network formation, demonstrating a functional effect of the altered trophoblast secretome. Treatment with sulfasalazine and metformin also restored angiogenic balance and organoid growth. Together, these findings establish a tractable human model that reproduces molecular and functional features of preeclampsia and provides a platform to study disease mechanisms and test potential therapies.
ER -