# Administrative Supplement to Intercellular interactions define cell migrations and transitions that maintain fetal membrane homeostasis

> **NIH NIH R01** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2020 · $280,934

## Abstract

ABSTRACT
Approximately 10.5% of all pregnancies end in preterm around the world. Spontaneous preterm birth (PTB)
and preterm birth due to preeclampsia (PE) contribute to both maternal and neonatal mortality and morbidity.
Current interventions for both these conditions are unsuccessful, and PTB and PE drug development has been
hindered by inability of drugs to cross the feto-maternal (F-M) barriers to treat both the mother and her fetus
and lack of proper ways of testing drug absorption, metabolism and cytotoxicity. Pathologically, PTB and a
large subset of PE have inflammation as a major mechanism driving preterm labor or contributing to placental
vascular pathology, respectively. Statins, competitive inhibitors of HMG-CoA reductase, have been shown to
reduce the expression of pro-inflammatory mediators. They have been successfully tested to reduce
inflammation and oxidative stress in both PTB and PE in vitro and animal models. Before these drugs can
advance to clinical trials, their efficacy and mechanism of action on the F-M and understanding their perfusion
kinetics across the F-M barriers are needed. However, current drug testing models have many limitations: 1)
the mouse F-M interface does not structurally mimic human, and chorionic trophoblast is obscure in the
mouse; 2) non-human primates models are cost prohibitive; 3) placental perfusions studies are restricted to the
placental-decidual interface, and thus drugs’ passage through the other interface is not tested, confounding
data and disrupting clinical trials. Besides, there are two distinct F-M interfaces: 1) between placenta and
decidua basalis and 2) between fetal membranes and decidua parietalis. Drugs and/or other metabolites must
pass through the two interfaces which are structurally and functionally very different. Therefore, simultaneous
testing of both F-M interfaces is necessary. To address these limitations, we will use F-M interface organ-on-
chips (OOCs) using cells from human tissues that can closely mimic the structure and functions of both F-M
interfaces. In this OOC model, we will test statins’ (rosuvastatin and pravastatin) properties and efficacy in
reducing inflammation.
 Aim 1 will test properties of drugs in two independent OOC models (placenta-decidua and fetal membrane-
 decidua interfaces).
 Aim 2 will recreate an inflammatory model of interfaces and test drugs’ efficacy.
 Aim 3 will integrate the two interfaces into one OOC device and test statins’ properties and efficacies.
OOC models generated can test the effect of candidate therapeutic molecules to more rapidly bring
experimental drugs (modeled using statins here) to streamline preclinical evaluation and minimize costs of
clinical trials.

## Key facts

- **NIH application ID:** 10177264
- **Project number:** 3R01HD100729-01S1
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** Arum Han
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $280,934
- **Award type:** 3
- **Project period:** 2020-03-12 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10177264

## Citation

> US National Institutes of Health, RePORTER application 10177264, Administrative Supplement to Intercellular interactions define cell migrations and transitions that maintain fetal membrane homeostasis (3R01HD100729-01S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10177264. Licensed CC0.

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