# Human heart-on-a-chip for screening cardiomyopathy and chemotherapeutic cardiotoxicity

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2020 · $578,025

## Abstract

Project Summary/Abstract:
Drug discovery and development are hampered by high failure rates attributed to the reliance on non-human
animal models employed during safety and efficacy testing. Even when drugs are approved there is a growing
concern that cancer chemotherapeutics result in cardiotoxicity via unknown mechanisms, making it difficult to
predict which patients will be affected. The discovery of human induced pluripotent stem (hiPS) cells has
enabled the tissue engineering community to develop in vitro human models of tissues and organs to be used
for high content drug screening and patient specific medicine. We envisage the device and stem cell
combinations proposed in this application will result in an in vitro microphysiological system (MPS) that
significantly reduces the cost of bringing a new drug candidate to market while improving efficacy. Specifically,
a physiologically functioning iPS-derived in vitro model of cardiac tissue (e.g., MPS) would be a significant
advancement for understanding cardiotoxicity (e.g., with chemotherapy), studying disease mechanisms, and
developing new strategies to treat cardiac diseases. As a basis for proof-of-principle of our methodology and
workflow, we have chosen to focus on illustrative forms of the most common cardiomyopathies, such as
hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). The principal goal of this proposal is
to establish an in vitro human cardiac MPS model based on geometric models of human ventricular
myocardium with populations of normal, genetically engineered, and disease specific hiPS cells differentiated
into cardiac myocytes (hiPS-CMs). We plan to assess in HCM and DCM lines the toxicity of chemotherapeutic
compounds that are currently on the market, FDA approved, and are known to cause mild or reversible cardiac
toxicity in some populations. A key strength of this proposal is that once we have calibrated our MPS with
isogenic hiPS-CMs, then we will proceed to testing hiPS-CMs from cardiomyopathy patients with diverse
backgrounds, as a step to using our MPS to advance the goals of personalized medicine. This comparison is
critical, as patient-derived iPS lines that have different genetic backgrounds have unknown effects on
physiology, so it is difficult to know if an altered response in our cardiac MPS is due to the disease, or normal
variation. We have proposed three specific aims to achieve our goals. If we are successful in completing our
Specific Aims, then our human in vitro MPS of cardiac tissue could be a powerful tool for screening
chemotherapeutic drug candidates for treatment, and reduce both the time and cost of the drug discovery
cycle.

## Key facts

- **NIH application ID:** 9861026
- **Project number:** 5R01HL130417-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** KEVIN Edward HEALY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $578,025
- **Award type:** 5
- **Project period:** 2017-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9861026

## Citation

> US National Institutes of Health, RePORTER application 9861026, Human heart-on-a-chip for screening cardiomyopathy and chemotherapeutic cardiotoxicity (5R01HL130417-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9861026. Licensed CC0.

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