# Stem Cell-based Human Placenta-on-a-Chip Using 3D Bioprinting

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $222,720

## Abstract

Supplement Project Summary
The placenta is the interface between mother and fetus, and as such controls the exchange of nutrients, waste
products, and therapeutic agents. The potential toxicity, teratogenicity, and therapeutic effects of drugs on the
fetus are controlled by their metabolism and clearance by maternal organs (particularly the liver and kidney),
their transport across the placenta, and their metabolism by the placenta. Given functional differences in these
properties between species, testing in animal models does not always predict adverse drug effects in human
pregnancy. Here, we propose to extend our parent project by adapting our model to investigate the role of the
placenta in drug transport, specifically, transport of nucleoside analogs such as remdesivir, which was recently
found to have efficacy against COVID-19.
The syncytiotrophoblast layer of the placenta is largely responsible for drug transport and metabolism. In our
model, human trophoblast stem cells (hTSCs) are seeded on the maternal side of the construct and allowed to
syncytialize. For this supplement project, we will introduce drugs that are known or suspected to be actively
transported across the placenta into the upper chamber, which represents the maternal blood space, and
examine the products that accumulate in the trophoblast cells or are transferred to the lower chamber, which
represents the placental villous capillaries on the fetal side. We propose to use this model to evaluate the
functional differences between wild type hTSCs and mutant hTSCs deficient in transporters that actively move
drugs in and out of trophoblast cells. With the recent publication reporting clinical benefit from remdesivir for
COVID-19, there is intense interest in the safety of this medication in pregnancy. Remdesivir is a nucleoside
analog that blocks SARS-CoV-2 replication, likely by inhibiting RNA-dependent RNA synthesis, as it does for the
related MERS coronavirus. The effects of remdesivir in pregnancy are unknown. In this project, we aim to use
CRISPR-Cas9 to knock out ENT1, CNT1, OCTN1, and MRP1 in hTSCs and evaluate the effects of these
mutations on transport of remdesivir and emtricitabine from the maternal to fetal compartment in our 3D placenta
model and accumulation of these drugs in the trophoblast cells. The proposed research will therefore accelerate
the understanding of transplacental permeability of antiviral drugs across the maternal-fetal barrier and elucidate
the involvement of transporters towards the development of therapeutics for use in pregnancy that are safe and
effective for both the mother and fetus, consistent with the objectives of the parent grant.

## Key facts

- **NIH application ID:** 10177137
- **Project number:** 3R21HD100132-02S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** SHAOCHEN CHEN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $222,720
- **Award type:** 3
- **Project period:** 2019-09-30 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10177137

## Citation

> US National Institutes of Health, RePORTER application 10177137, Stem Cell-based Human Placenta-on-a-Chip Using 3D Bioprinting (3R21HD100132-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10177137. Licensed CC0.

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