# Placental Organoids for Modeling and Treating Preeclampsia

> **NIH NIH R21** · CEDARS-SINAI MEDICAL CENTER · 2022 · $49,030

## Abstract

While the underlying etiology of preeclampsia (a hypertensive disorder of pregnancy)
is not known, the disease starts with shallow placentation and placental ischemia which in
turn releases excess of anti-angiogenic proteins such as soluble fms-like tyrosine kinase 1
(sFLT1) in the mother's bloodstream that is responsible for the systemic maternal endothelial
dysfunction. Self-renewing 3D epithelial organoids that closely resemble the structure and
physiology of the original organ have been successfully developed into various tissue
types using human induced pluripotent stem cells (hiPSCs). However, organoids of the
human placental trophoblasts using hiPSCs are yet to be generated. Our goal of this
proposal is to generate trophoblast organoids from disease-specific hiPSCs to study
preeclampsia pathogenesis and to screen for drugs as potential treatment targets. We
will generate a new model of trophoblast organoid using hiPSCs, replicating the early
stage of gestation from normal and preeclamptic pregnancies, a time in development that
has – until now – has been mostly inaccessible to researchers. In aim 1, we will optimize
trophoblast organoid protocols in our laboratory using hiPSCs derived trophoblast
differentiation method from donor fibroblasts and will confirm that these organoids
phenotypically and functionally behave like first trimester villous tissue. We will then test the
hypothesis that the functional capacity of trophoblast organoids derived from hiPSCs obtained
from early-onset preeclampsia will be impaired when compared to trophoblast organoids
derived from non-hypertensive controls. In aim 2, we will model maternal syndrome of
preeclampsia in nude mice with factors made by human placenta. To model human
preeclampsia, we will generate trophoblast organoids using hiPSCs derived from placental
fibroblasts from women carrying a fetus with trisomy 13, a disorder characterized by 10-fold
excess risk of preeclampsia due to extra copy of sFLT1 gene from chromosome 13. We will
then test in vivo efficacy of monoclonal antibodies that target the unique C-terminus of human
sFLT1-i14 (the isoform that is primate-specific) for enhanced clearance of sFLT1 from
systemic circulation. Due to the organoid's ready access and ability to replicate the early
stages of development from well-characterized cells, the trophoblast organoid model
promises to significantly improve our understanding of preeclampsia and provides rapid
screening methods for testing potential drugs and furthering precision medicine methods
in obstetrics.

## Key facts

- **NIH application ID:** 10464766
- **Project number:** 1R21HD108867-01
- **Recipient organization:** CEDARS-SINAI MEDICAL CENTER
- **Principal Investigator:** S. Ananth Karumanchi
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $49,030
- **Award type:** 1
- **Project period:** 2022-09-22 → 2022-12-17

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10464766

## Citation

> US National Institutes of Health, RePORTER application 10464766, Placental Organoids for Modeling and Treating Preeclampsia (1R21HD108867-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10464766. Licensed CC0.

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