# Effect of Microgravity on Drug Responses Using Engineered Heart Tissues

> **NIH NIH UH3** · STANFORD UNIVERSITY · 2022 · $196,612

## 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:** 10670018
- **Project number:** 3UH3TR002588-04S1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Beth L Pruitt
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $196,612
- **Award type:** 3
- **Project period:** 2022-07-22 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10670018

## Citation

> US National Institutes of Health, RePORTER application 10670018, Effect of Microgravity on Drug Responses Using Engineered Heart Tissues (3UH3TR002588-04S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10670018. Licensed CC0.

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