# Modeling Preeclampsia Using Human Pluripotent Stem Cells

> **NIH NIH R00** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $249,000

## Abstract

Project Summary/Abstract
Placenta is a transient organ that connects mom and baby during pregnancy, and supplies nutrients and
oxygen for intrauterine fetal growth. It has been known that abnormal placentation can lead to preeclampsia
(PE), a major complication affecting 2-8% of all pregnancies, presenting as new onset hypertension and
proteinuria in the latter half of pregnancy. PE is associated with growth restriction and preterm delivery of the
baby, both of which are associated with adverse outcomes, in both the perinatal period and later in life. Many
studies point to abnormal differentiation of placental epithelial cells, called trophoblast, as the etiology of PE.
Specifically, development of invasive extravillous trophoblast (EVT) and/or their function are affected in PE,
leading to shallow implantation and placental insufficiency. However, while these are some accepted
hypotheses about the nature of the disease, the underlying pathophysiology is still not fully understood mainly
due to the lack of a truly representative model system. Over the past decade, the development of methods to
generate induced pluripotent stem cells (iPSC) has led to the ability to model numerous human diseases,
including those originating in the cardiovascular and nervous systems and the pancreas. In addition, over the
same time period, multiple groups, including ours, have shown that iPSCs can be differentiated into
trophoblast, using the growth factor, bone morphogenetic protein 4 (BMP4). My own work has in fact provided
proof-of-concept that defects in trophoblast differentiation, specifically those associated with Trisomy 21, can
be modeled using iPSCs. I therefore plan to apply this technology to model placental dysfunction in PE, with
the following three aims: 1) I will establish iPSCs by reprogramming umbilical cord mesenchymal stem cells
(UC-MSCs) from six PE and six gestational age-matched control (non-PE) placentas, using non-integrative
Sendai virus-based method. I will assay their pluripotency, and characterize their epigenetic memory before
and after reprogramming, evaluating both DNA methylation and histone H3 modifications. 2) I will characterize
the trophoblast derived from both PE and control iPSCs, evaluating their ability to differentiate into both
invasive EVT and multinucleated syncytiotrophoblast (STB). I will also evaluate both the gene expression and
epigenetic profile of trophoblast derived from PE and non-PE iPSC. 3) Finally, I will test the effect of
environmental factors, known to be involved in the pathogenesis of PE, on trophoblast derived from PE and
non-PE iPSCs, including the effects of hypoxia, pro-inflammatory cytokines, and specific subpopulations of
decidual leukocytes. The successful completion of this project will provide us with new models for studying this
devastating disease, and thus the ability to generate novel diagnostic tools and therapeutic modalities in order
to improve care for these women and babies.

## Key facts

- **NIH application ID:** 10140719
- **Project number:** 4R00HD091452-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Mariko Horii
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $249,000
- **Award type:** 4N
- **Project period:** 2020-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10140719

## Citation

> US National Institutes of Health, RePORTER application 10140719, Modeling Preeclampsia Using Human Pluripotent Stem Cells (4R00HD091452-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10140719. Licensed CC0.

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