# Advances in Epicardial Biology: Insights from Development, Regeneration, and Human Cardiac Organoids

## TL;DR

This paper reviews recent discoveries about the epicardium's role in heart development and repair, using advanced models like human cardiac organoids.

## Contribution

The paper integrates developmental, regenerative, and human organoid data to present a new framework for epicardial biology.

## Key findings

- Human cardiac organoids reveal epicardial cell heterogeneity and developmental plasticity.
- Epicardial function mechanisms show conservation and divergence across species.
- Epicardial interactions with myocardial, endothelial, and immune cells regulate cardiac repair.

## Abstract

The epicardium plays a pivotal role in heart development, regeneration, and disease response through its contributions to multiple cardiac lineages and its dynamic paracrine signaling. Recent advances in lineage tracing, single-cell technologies, and, particularly, human pluripotent stem cell (hPSC)-derived cardiac organoid models have illuminated the cellular heterogeneity, developmental plasticity, and intercellular crosstalk of epicardial cells with other cardiac cell types. These models have revealed conserved and divergent mechanisms of epicardial function across species, offering new insights into epicardial–myocardial–endothelial–immune interactions and the regulation of cardiac repair. This review highlights recent key findings from developmental and regenerative studies, integrating them with emerging data from human cardiac organoids to provide an updated framework for understanding epicardial biology and its therapeutic potential.