# Modeling human trophoblast-NK cell interactions in term and preterm birth

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2023 · $158,000

## Abstract

Project Summary/Abstract
The human placenta is a semi-allogeneic tissue whose growth and development requires tolerance by the
maternal immune system. In fact, the maternal immune system faces a challenge during pregnancy: to
maintain tolerance toward foreign fetal alloantigens while simultaneously staging a response to potential
pathogens at the maternal-fetal interface. The mechanisms through which placental cells evade maternal
immune recognition are poorly understood, particularly in the context of human pregnancy. The uterine
lining, called decidua, is a particularly-understudied and important microenvironment, because it is the
interface where placental cells called extravillous trophoblast (EVT) come in close contact with maternal
immune cells, of which decidual natural killer (dNK) cells are the most abundant. EVT are highly invasive
cells which are required for proper remodeling of the maternal uterine lining, including vascular
remodeling which leads to establishment of maternal blood flow to the placenta. Interactions between
placental EVT and decidual leukocytes are known to facilitate maternal vascular remodeling by EVT and
limit the extent of EVT invasion into the uterine wall. Indeed, problems in preterm birth could result from
inappropriate responses by dNK cells. Unfortunately, interactions between dNK and trophoblasts are
difficult to study in an ongoing pregnancy, due to lack of access to the decidual compartment, where these
important interactions occur. While animal models have offered some insights into these processes, they
do not accurately model human placentation and pregnancy. The goal of the original R01 proposal is to
evaluate the decidual cell population in both term and preterm birth, then to combine this knowledge with
the latest technologies in regenerative medicine to develop in vitro models for the study of dNK-EVT
interactions. Specifically, we proposed to generate matched maternal and placental induced pluripotent
stem cells (iPSC), and differentiate these cells into dNK cells and EVT, respectively, in order to model
interactions between these two cell types. Given the known association between male fetal sex and risk of
preterm birth, we had focused our efforts on characterizing, banking, and reprogramming cells from
mom:male baby pairs in the original application. However, to fully understand mechanisms that
predispose to sPTB, it would be best to compare these data to those from mom:female baby pairs.
Therefore, we now propose to characterize, bank, and reprogram cells from mom:female placenta
pairs for this administrative supplement. Successful completion of this proposal will establish a
reproducible and manipulatable model system for studying interactions between the maternal immune
system and both the male and female placenta.

## Key facts

- **NIH application ID:** 10770207
- **Project number:** 3R01HD102639-03S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Jack D Bui
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $158,000
- **Award type:** 3
- **Project period:** 2023-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10770207

## Citation

> US National Institutes of Health, RePORTER application 10770207, Modeling human trophoblast-NK cell interactions in term and preterm birth (3R01HD102639-03S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10770207. Licensed CC0.

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