Engineered trophoblast organoids recapitulate molecular and functional features of preeclampsia

Genetically engineered human trophoblast organoids expressing the sFlt-1 exon 15a isoform develop an elevated sFlt-1/PlGF ratio comparable to primary preeclamptic trophoblast organoids.

• Why it matters: Preeclampsia research is constrained by limited access to patient placental tissue and by models that do not fully mirror human disease biology.
• What they did: Induced trophoblast stem cells were engineered with a CRISPR-based Prime Integrase strategy to express the preeclampsia-associated sFlt-1 exon 15a isoform, then organoids were assessed for transcriptional, secretome, and growth/oxidative-stress changes.
• The result: Engineered organoid conditioned media impaired endothelial network formation, while sulfasalazine and metformin restored angiogenic balance and organoid growth, enabling mechanistic study and therapy testing.

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