Zebrafish Heart Regeneration as a Model for Cardiac Tissue Repair

Drug Discov Today Dis Models, 2007 · DOI: 10.1016/j.ddmod.2007.09.002 · Published: January 1, 2007

Cardiovascular Science Regenerative Medicine Research Methodology & Design

Simple Explanation

Heart disease is a major cause of death, and mammals have limited heart repair abilities. Zebrafish, however, can regenerate heart tissue, making them a good model for studying regeneration. Future research on zebrafish heart regeneration could help unlock our own regenerative potential. Unlike mammals, the injured zebrafish heart normally undergoes minimal scarring. Instead, a transient fibrin clot is replaced with new contractile muscle. This review will focus on recent progress in the field of cardiac regeneration with an emphasis on the zebrafish model system. Zebrafish heart regeneration proceeds through injury-induced proliferation of cardiomyocytes. Recent work suggests that regenerating myocardium matures from undifferentiated, Cmlc2-negative, progenitor cells at the leading edge.

Study Duration

1-2 months

Participants

Zebrafish

Evidence Level

Not specified

Key Findings

1
Zebrafish heart muscle can regenerate after injury with minimal scarring, replacing lost tissue with new contractile muscle.
2
The epicardium, the outer layer of the heart, plays a crucial role in zebrafish heart regeneration, undergoing a rapid and dynamic response to injury.
3
Fibroblast growth factor (FGF) signaling is necessary for epicardial cell activity during zebrafish heart regeneration, directing the EMT of epicardial-derived cells.

Research Summary

Mammals have a limited capacity for heart regeneration, unlike zebrafish. Zebrafish can regenerate heart tissue after injury, making them a valuable model for studying cardiac regeneration. Zebrafish heart regeneration involves the proliferation of cardiomyocytes and the activation of progenitor cells. The epicardium, the outer layer of the heart, plays a crucial role in this process. FGF signaling and Thymosin- 4 are important factors in zebrafish heart regeneration. These factors promote neovascularization and the differentiation of epicardial cells.

Practical Implications

Understanding Cardiac Progenitor Cells

Further research can help understand how cardiac progenitor cells are successfully utilized for regeneration.

Optimizing Epicardial Activation

Further research can help understand how the epicardium is optimally activated and directed to support regeneration.

Translational Potential

Increased resolution of regenerative pathways may bring the idea of cardiac regeneration in humans closer to reality.

Study Limitations

1
The current zebrafish injury models produce a mechanical injury, which might not fully mimic the infarct models utilized in mammals.
2
It is not known from what source(s) these apparent progenitor cells are derived.
3
Lineage analyses will be necessary to determine possible contributions of dedifferentiation.

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