# Establishing an In Vitro Embryotoxicity Risk Classification System Based on Human Cardiac Organoid Model

> **NIH NIH R01** · SYRACUSE UNIVERSITY · 2021 · $446,702

## Abstract

Project Summary
Currently, drug embryotoxicity risk for safe pregnancy is not well established, thus many pregnant women are
exposed to the drugs with unknown effects on fetus development. Many drugs are still neither well understood
regarding their effects on human organogenesis, nor is there a well-established human embryotoxicity drug
screening platform available. Currently, human induced pluripotent stem cells (hiPSCs) have been proposed for
human-relevant drug toxicity screening. However, the use of hiPSC maintenance and differentiation on 2D
culture is not an ideal embryotoxicity assay due to their inability to predict the drug toxicity on 3D tissue
morphogenesis, which potentially leads to the structural malformations manifested in late prenatal fetus
development. With the emergent concept of stem cell organoids, these 3D cultures of developing tissues imply
the similarity to the manner in which different organs establish their characteristic organization during
development. Therefore, the overall goal of this proposal is to establish an in vitro hiPSC-based cardiac organoid
model for embryotoxicity testing based on the drug effects on hiPSC growth, cardiac differentiation, and early
heart formation, so we can establish a risk classification system for more precise assessment of human-specific
drug effects on early embryonic development. To achieve this goal, we will pursue three specific aims. In Aim 1,
we will optimize the cardiac organoid model by investigating the effects of biophysical confinement on the
formation and function of cardiac organoids. In Aim 2, we will validate the cardiac organoid-based embryotoxicity
assay by comparing to well-established standard zebrafish whole embryo culture assay. By testing a “training
set” of chemicals with known embryotoxicity level, we will better calibrate the drug response from human cardiac
organoids based on a variety of endpoint evaluation parameters. In Aim 3, we will establish a new biostatistical
predictive model based on linear discriminant analysis for embryotoxicity risk classification. We envisage that
this in vitro cardiac organoid model can improve traditional pharmaceutical screening for the drugs that will be
administered during pregnancy.

## Key facts

- **NIH application ID:** 10133110
- **Project number:** 5R01HD101130-02
- **Recipient organization:** SYRACUSE UNIVERSITY
- **Principal Investigator:** Zhen Ma
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $446,702
- **Award type:** 5
- **Project period:** 2020-04-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10133110

## Citation

> US National Institutes of Health, RePORTER application 10133110, Establishing an In Vitro Embryotoxicity Risk Classification System Based on Human Cardiac Organoid Model (5R01HD101130-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10133110. Licensed CC0.

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