# Self-assembling cardiac organoids to model myovascular interactions in human cardiac tissue regeneration

> **NIH NIH F30** · DUKE UNIVERSITY · 2024 · $53,974

## Abstract

Abstract
Heart failure is a leading cause of death worldwide and there is a critical, unmet need for non-surgical
therapies. A key barrier to developing curative therapy is that the human heart, unlike that of zebrafish,
axolotls, and some neonatal mammals, lacks the ability to recover after acute or chronic injury. Our lab has
discovered that in neonatal mice, which can regenerate the heart after injury, cardiomyocytes and endothelial
cells proliferate in a spatiotemporally coordinated manner. When key cell-cell signaling factors are lost, such as
VEGFA or its receptor VEGFR2, we observe significantly decreased rates of cell cycling in both
cardiomyocytes and endothelial cells. This suggests that local signals between these cells are responsible for
inducing and maintaining a proliferative state in the neonatal period. For this information to be therapeutically
translational, however, we must understand whether these mechanisms are conserved in human cells. We
have devised a cardiac organoid (CO) platform enriched for endothelial cells that can be used to model human
myovascular interactions. With this model, we will use cardiomyocyte and endothelial cell reporters and live
imaging to investigate how modifying endothelial cell content within a human CO impacts organoid function
and regeneration after ischemia-reperfusion injury. In addition, we will use a CRISPRa lentiviral construct to
overexpress key factors secreted by cycling endothelial cells, with cognate receptors on cycling
cardiomyocytes, for effects on cardiomyocyte proliferation. This proposal details the use of a high-throughput
CO platform to disentangle the complexities of myovascular interactions in human cells, enabling discovery
and validation of novel therapeutic targets.

## Key facts

- **NIH application ID:** 10994876
- **Project number:** 1F30HL175908-01
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Lauren Elizabeth Parker
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $53,974
- **Award type:** 1
- **Project period:** 2024-09-30 → 2027-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10994876

## Citation

> US National Institutes of Health, RePORTER application 10994876, Self-assembling cardiac organoids to model myovascular interactions in human cardiac tissue regeneration (1F30HL175908-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/10994876. Licensed CC0.

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