{
  "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.",
  "abstract_shown": true,
  "affiliations": [
    "Flinders University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "A. L. Arthurs"
    },
    {
      "name": "C. Lushington"
    },
    {
      "name": "D. L. Medina Garcia"
    },
    {
      "name": "A. L. Merriman"
    },
    {
      "name": "G. A. Mora-Roldan"
    },
    {
      "name": "L. Parry"
    },
    {
      "name": "A. Boparai"
    },
    {
      "name": "J. M. Polo"
    },
    {
      "name": "F. L. Adikusuma"
    },
    {
      "name": "P. Q. Thomas"
    },
    {
      "name": "C. T. Roberts"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dk11v87a26d0z.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.07.22.739976",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.07.22.739976v2.full",
  "id": "dk11v87a26d0z",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.07.22.739976v2",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cell biology"
    ],
    [
      "openalex",
      "2729|Pregnancy and preeclampsia studies"
    ]
  ],
  "openalex": "W7170041195",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.07.22.739976v2.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-07-22",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/dk11v87a26d0z.ris",
  "sources": [
    {
      "first_seen": "2026-11-02T12:20:49Z",
      "native_id": "10.64898/2026.07.22.739976",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.07.22.739976v2"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:cell biology",
      "subfield": "cell-biology"
    }
  ],
  "title": "Engineered trophoblast organoids recapitulate molecular and functional features of preeclampsia",
  "title_text": "Engineered trophoblast organoids recapitulate molecular and functional features of preeclampsia",
  "type": "preprint",
  "updated_at": "2026-11-03T00:20:31Z",
  "url": "https://research.draconitic.com/paper/dk11v87a26d0z",
  "venue": "bioRxiv",
  "versions": []
}