Key Takeaways & Executive Findings
- •• Epicardial EMT is a critical process in cardiac development and repair, involving epithelial cells transitioning to mesenchymal phenotypes to contribute to cardiac cell types and paracrine signaling. • Endogenous epicardial EMT is insufficient for adequate cardiac repair, necessitating strategies to amplify or redirect EMT pathways for therapeutic benefit. • Reactivation of epicardial EMT in adult heart disease patients represents a promising avenue for innovative treatments. • Understanding the molecular mechanisms of EMT is essential for developing effective cardiac regeneration therapies.
Abstract
Epicardial epithelial-to-mesenchymal transition (EMT) plays a pivotal role in both heart development and injury response and involves dynamic cellular changes that are essential for cardiogenesis and myocardial repair. Specifically, epicardial EMT is a crucial process in which epicardial cells lose polarity, migrate into the myocardium, and differentiate into various cardiac cell types during development and repair. Importantly, following EMT, the epicardium becomes a source of paracrine factors that support cardiac growth at the last stages of cardiogenesis and contribute to cardiac remodeling after injury. As such, EMT seems to represent a fundamental step in cardiac repair. Nevertheless, endogenous EMT alone is insufficient to stimulate adequate repair. Redirecting and amplifying epicardial EMT pathways offers promising avenues for the development of innovative therapeutic strategies and treatment approaches for heart disease. In this review, we present a synthesis of recent literature highlighting the significance of epicardial EMT reactivation in adult heart disease patients.
1. Introduction
Over the last decade, several strategies have been applied to promote cardiac repair, including stimulation of cardiomyocyte cell cycle re-entry, treatment with stem/progenitor cells or stem cell-derived cardiomyocytes, modulation of tissue repair using cytokines and growth factors, and tissue engineering approaches [1, 2]. An improved understanding of the molecular mechanisms driving cardiomyocyte (CM) proliferation and differentiation and, importantly, the role of noncardiomyocytes in supporting cardiac function is critical for achieving significant cardiac regeneration.
Processes occurring during cardiac development are often recapitulated in the disease setting. For this reason, many efforts have been devoted to the development of new strategies capable of modulating these processes to bolster tissue repair. The epithelial-to-mesenchymal transition (EMT) is a fine representation of this phenomenon. Specifically, recent findings support the involvement of epicardial EMT in cardiac repair and regeneration by providing progenitor cells with the ability to differentiate into different cardiac cell phenotypes and secrete paracrine factors [3–5].
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Eleonora Foglio, Erica D’Avorio, Riccardo Nieri, Matteo Antonio Russo, Federica Limana (2026). Epicardial EMT and cardiac repair: an update. Stem Cell Research & Therapy. https://doi.org/10.1186/s13287-024-03823-z
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Frequently Asked Questions
What is epicardial EMT?
Epicardial EMT is a process where epicardial cells lose epithelial features and acquire mesenchymal properties, allowing them to migrate into the myocardium and differentiate into various cardiac cell types, contributing to heart development and repair.
Why is epicardial EMT important for cardiac repair?
Epicardial EMT provides progenitor cells that can differentiate into cardiac cells and secrete paracrine factors that support cardiac growth and remodeling after injury, making it a fundamental step in cardiac repair.
Is endogenous epicardial EMT sufficient for cardiac repair?
No, endogenous EMT alone is insufficient to stimulate adequate repair. Therefore, strategies to amplify or redirect EMT pathways are being explored for therapeutic purposes.
What are the potential therapeutic applications of epicardial EMT?
By modulating epicardial EMT, it may be possible to enhance cardiac regeneration and repair in heart disease patients, offering new treatment approaches.
What is the role of paracrine factors in epicardial EMT?
Following EMT, epicardial cells secrete paracrine factors that support cardiac growth and contribute to cardiac remodeling, which is crucial for repair after injury.
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