# Defining the role of non-myocytes to achieve biologically relevant engineered myocardial tissues

> **NIH NIH R03** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2021 · $84,750

## Abstract

Project Summary
There is an urgent need to develop novel treatments for heart failure. The clinical translation of novel therapies
for cardiac disease is hindered by the limited availability of suitable models of the human heart. The use of
human engineered cardiac tissues (hECTs) can serve to bridge the gap between current animal models,
providing a species-specific model of human myocardium, and also overcomes limitations of the 2D culture
systems. The field of cardiac tissue engineering is constantly evolving, with the proposition of novel strategies
for the fabrication of a structurally and functionally mature model of human myocardium. These technologies
have been favored by the optimization of methodologies for the differentiation of human induced pluripotent stem
cells (hiPSC) into cardiomyocytes and non-myocyte cell types. Healthy cardiac development and function is
supported by a complex network of interactions between diverse cell types, including cardiomyocytes,
nonmyocytes, and the extracellular matrix. The objective of this study is to utilize a combination of
cardiomyocytes (CM) and nonmyocytes with a matrix polymer mix to fabricate engineered myocardium (EngMyo)
with functional and structural properties of the native human myocardium, along with a better representation of
its cellular milieu, with the long-term goal of using these as in vitro models to test novel therapies that could
impact cardiac function. We hypothesize that the presence of non-myocytes in the proper ratios, will result in
enhanced functional and structural characteristics when compared to myocardial tissues fabricated with CM
alone, mainly through the activation of signaling pathways associated with cardiomyocyte development and cell
turnover. We will address this hypothesis in two aims. In Aim 1, we will test the prediction that the contractility
of cardiomyocytes grown in 3D is impacted by crosstalk with non-myocyte cells. First, we will differentiate hiPSC
into CM, fibroblasts, endothelial, and smooth muscle cells, followed by characterization using flow cytometry and
immunofluorescence. Then we will manipulate the type and number of cells that will be combined to fabricate
engineered myocardium (EngMyo), and for each resulting EngMyo we will perform functional and structural
characterization. Our central hypothesis predicts that the presence of non-myocytes in the proper ratios, will
result in enhanced contractile force than EngMyo fabricated with hCM alone. We will determine which is the cell
combination that provides the largest enhancement in force. In Aim2 we will identify the molecular pathways
activated by the presence of non-myocytes. We will perform RNAseq in the EngMyo fabricated with CM-only
(control) and EngMyo fabricated with combination of CMs and non-cardiomyocyte cells. We will investigate which
are the differentially expressed genes and from this analysis we seek to identify the signaling pathways activated
by the presence of non-myocytes. T...

## Key facts

- **NIH application ID:** 10249331
- **Project number:** 5R03HL154286-02
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Irene Cal y Mayor-Turnbull
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $84,750
- **Award type:** 5
- **Project period:** 2020-09-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10249331

## Citation

> US National Institutes of Health, RePORTER application 10249331, Defining the role of non-myocytes to achieve biologically relevant engineered myocardial tissues (5R03HL154286-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10249331. Licensed CC0.

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