# Effect of Microgravity on Drug Responses Using Engineered Heart Tissues

> **NIH NIH UH3** · STANFORD UNIVERSITY · 2021 · $714,532

## Abstract

PROJECT SUMMARY
Tissue engineered organs or functional tissue-like ensembles contribute significantly to our understanding of
cellular niches that allow cells to migrate, develop and mature in three dimensions (3-D). Conventional two-
dimensional (2-D) mammalian cell culture does not represent the physiological environments that form the basis
for normal cell function. A 3-D environment promotes isotropic cell-cell communications, provides extracellular
guidance from structural matrix scaffolding, and allows spatiotemporal remodelling. Our specific interest is in
investigating the effects of microgravity on heart function with the use of Engineered Heart Tissues (EHTs). Since
these tissue engineering platforms support multicellular architecture from a ‘bottom-up’ approach, it is critical to
understand the mechanisms of heart development from a primordial state. Although animal models are used
widely to investigate biological responses to therapeutics, inherent differences between human and animal
biology combined with the unlikelihood of animals developing a human disease limit the ability to validate
research findings. Human induced pluripotent stem cells (hiPSCs) have emerged as an indispensable tool to
drive cells from an embryonic state to any somatic cell type. Our laboratory’s focus and expertise in generating
hiPSC-derived cardiomyocytes (hiPSC-CMs) and modelling of cardiomyopathies has yielded deeper insight into
several rare and common causes of heart failure. To maintain a tissue-specific microenvironment, dissociated
cells must be cultured in a physiologically relevant 3-D extracellular matrix (ECM). In the first phase (UG3), we
will generate hiPSC-CMs from healthy patients belonging to diverse racial groups (Caucasians, Hispanics, and
African Americans). The hiPSC-CMs will be used to fabricate our well-characterized EHT platforms, to
understand cellular mechanisms that affect cardiac function both under microgravity and earth’s gravity.
Alterations in cardiac function due to weakened heart muscles in the samples exposed to microgravity will be
matched with molecular and electrophysiological disease patterns observed in ischemic cardiomyopathy. In the
second phase (UH3), the well-characterized microgravity-induced disease phenotype will be translated on Heart
Tissue Arrays (HTA) to screen for potential drug candidates in a high-throughput manner. The proposed study
will for the first time reveal key functional and molecular differences that drive phenotypic changes in heart tissues
on EHT assemblies under influence of microgravity.

## Key facts

- **NIH application ID:** 10239266
- **Project number:** 5UH3TR002588-04
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Beth L Pruitt
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $714,532
- **Award type:** 5
- **Project period:** 2018-09-18 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10239266

## Citation

> US National Institutes of Health, RePORTER application 10239266, Effect of Microgravity on Drug Responses Using Engineered Heart Tissues (5UH3TR002588-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10239266. Licensed CC0.

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