# Heterotypic impacts of epicardial cells on engineered cardiac microtissue function

> **NIH NIH R15** · STATE UNIVERSITY OF NY,BINGHAMTON · 2020 · $449,629

## Abstract

PROJECT SUMMARY
Human pluripotent stem cells represent a potentially unlimited source of cardiomyocytes (CMs) for the study of
cardiovascular development and disease, as well as for use in regenerative therapies. Tissue engineering
enables the generation of three-dimensional constructs that mimic native cardiac structure and function and
serve as substrates for therapeutic development and biological interrogation. However, during native cardiac
development, cardiomyocytes interact directly with other cell types such as epicardial cells (EpiCs) and cardiac
fibroblasts (CFs) to achieve physiologic function. In order for engineered cardiac tissues to fully recapitulate
native myocardium, they require the addition of cardiac non-myocyte cells. Although it is well appreciated that
these non-myocyte cells contribute to stable tissue formation and can modulate cardiac function, the specific
role of epicardial cells and epicardial-derived cardiac fibroblasts on cardiac microtissue function remains
unknown. Thus, our primary objective of this project is to determine how bi-directional influences of epicardial-
derived CFs and CMs affect engineered cardiac microtissue function and organization. Our central hypothesis
is that heterotypic interactions between epicardial-derived CFs and CMs are critical to promote phenotypic and
functional maturation of engineered cardiac tissues. This hypothesis is based on our ability to engineer cardiac
microtissues of controlled compositions of CMs, EpiCs, or EpiC-CF. Specifically, in Aim 1 we will evaluate the
phenotype of CFs that have been derived from human pluripotent stem cells through an epicardial intermediary
step and determine their similarity to native CFs. In Aim 2 we will evaluate the heterotypic effects of epicardial-
derived cardiac fibroblasts on engineered cardiac tissue function. In Aim 3, we will determine if heterotypic
interactions with CMs induce epithelial-to-mesenchymal transition of epicardial cells, enabling cardiac fibroblast
invasion of engineered cardiac constructs. Successful completion of this project will give insight into the
specific roles epicardial cells and epicardial-derived fibroblasts have in promoting cardiac physiologic function.
Armed with this knowledge, more accurate in vitro models of cardiac tissue can be achieved, enabling the
study of human cardiac diseases.

## Key facts

- **NIH application ID:** 9880756
- **Project number:** 1R15HL150745-01
- **Recipient organization:** STATE UNIVERSITY OF NY,BINGHAMTON
- **Principal Investigator:** Tracy Hookway
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $449,629
- **Award type:** 1
- **Project period:** 2020-02-10 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9880756

## Citation

> US National Institutes of Health, RePORTER application 9880756, Heterotypic impacts of epicardial cells on engineered cardiac microtissue function (1R15HL150745-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9880756. Licensed CC0.

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