# Stem Cell-based Modeling of Placental Defects associated with Early-Onset Preeclampsia

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $616,853

## Abstract

Project Summary/Abstract
Preeclampsia (PE) is a multifactorial pregnancy syndrome that affects up to 10% of pregnancies worldwide,
and is defined by new onset of hypertension and proteinuria or end-organ dysfunction appearing after 20
weeks of gestation. Although the well-accepted underlying pathophysiology of this disease involves both
maternal and fetal/placental factors, the symptoms resolve following the delivery of the placenta pointing to
the importance of placental involvement in this disease. The placental histological phenotype of PE is known
to have a wide range of lesions. Maternal vascular malperfusion (MVM), one of the predominant placental
injuries associated with PE, is known for abnormal syncytiotrophoblast and extravillous trophoblast
differentiation and function, with some cases overlapping with fetal vascular malperfusion (FVM). However,
the detailed underlying molecular and cellular pathophysiology associated with PE placenta showing MVM,
with or without FVM, is not well-understood. Therefore, we have set the following three aims in this proposal,
combining a novel trophoblast modeling system, the molecular characterization of the placenta, and
evaluate influence of mesenchymal stem/stromal cells (MSC) at the chorionic villi and elucidate the detailed
mechanism associated with this pathology. Aim 1 will identify the optimal stem cell-based method to study
abnormal trophoblast differentiation in PE placenta. Aim 2 will focus on in-depth characterization of PE-
MVM placentas with or without FVM, and bank and characterize the cellular phenotype of each MVM
subtypes of umbilical cord-derived MSCs. Aim 3 will evaluate the trophoblast-MSC crosstalk within the
chorionic villi of PE placentas with different MVM-subtypes. The successful completion of this proposal will
establish subtype-specific cell-based models of PE, providing effective tools for identifying diagnostic
biomarkers and therapeutic targets for each sutypes, leading us to the better pregnancy care for woman
and babies.

## Key facts

- **NIH application ID:** 10858736
- **Project number:** 1R01HD114720-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Mariko Horii
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $616,853
- **Award type:** 1
- **Project period:** 2024-07-01 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10858736

## Citation

> US National Institutes of Health, RePORTER application 10858736, Stem Cell-based Modeling of Placental Defects associated with Early-Onset Preeclampsia (1R01HD114720-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10858736. Licensed CC0.

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