# High-throughput assessment of chemotherapy-induced cardiotoxicity in 3D human cardiomyocytes

> **NIH NIH R21** · EMORY UNIVERSITY · 2024 · $402,403

## Abstract

High-throughput assessment of chemotherapy-induced cardiotoxicity in human cardiospheres
Project Summary
Chemotherapeutic agents including both traditional drugs (e.g., anthracyclines) and newer ones (e.g.,
proteasome inhibitors) are associated with cardiac adverse events including increased risk of arrhythmias.
Treatment for arrhythmias is difficult with currently available antiarrhythmic drugs. Development of effective
therapies is therefore highly desirable and can be facilitated by human cell models and high-throughput assays.
Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) have provided a new platform
for the studies of drug-induced side effects and disease modeling. hiPSC-CMs have translational potential to
improve current models by providing clinically relevant characteristics regarding disease phenotypes and
responses to drug treatment. They can also overcome the differences between human and animal cardiac
physiology and challenges in long-term maintenance of primary human cardiomyocytes.
Ca2+ handling abnormalities play a central role in the pathophysiology of heart failure and arrhythmias and could
be promising targets for novel therapeutics to treat chemotherapy-induced cardiotoxicity, since chemotherapy
can cause Ca2+ to be released spontaneously at the wrong times during the heartbeat, thus inducing arrhythmias.
Our objective is to achieve an accurate and high-throughput Ca2+ transient recoding and analyses for functional
assessment of 3D hiPSC-CMs (cardiospheres). We expect that this technology will allow us to detect
chemotherapy-induced cardiotoxicity and evaluate potential therapies in a highly efficient manner. Our proposed
study is an important component for the application of hiPSC-CMs in the study of chemotherapy-induced
cardiotoxicity.
Using our state-of-the-art equipment and computational tools, we aim to (1) establish high-throughput functional
assessment of human cardiospheres for the detection of chemotherapy-induced cardiotoxicity, and (2) evaluate
novel antiarrhythmic therapies to mitigate chemotherapy-induced cardiotoxicity. The human cardiospheres will
provide a better model for chemotherapy-induced arrhythmias, since clinical arrhythmias result from the
collective behavior of cardiomyocytes within cardiac tissues. We expect that our high throughput functional assay
will facilitate the discovery of novel therapeutic targets.

## Key facts

- **NIH application ID:** 10936818
- **Project number:** 1R21CA285254-01A1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Chunhui Xu
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $402,403
- **Award type:** 1
- **Project period:** 2024-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10936818

## Citation

> US National Institutes of Health, RePORTER application 10936818, High-throughput assessment of chemotherapy-induced cardiotoxicity in 3D human cardiomyocytes (1R21CA285254-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10936818. Licensed CC0.

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