Cardiac Neural Crest and Cardiac Regeneration

Abstract

Neural crest cells (NCCs) are a vertebrate-specific, multipotent stem cell population that have the ability to migrate and differentiate into various cell populations throughout the embryo during embryogenesis. The heart is a muscular and complex organ whose primary function is to pump blood and nutrients throughout the body. Mammalian hearts, such as those of humans, lose their regenerative ability shortly after birth. However, a few vertebrate species, such as zebrafish, have the ability to self-repair/regenerate after cardiac damage. Recent research has discovered the potential functional ability and contribution of cardiac NCCs to cardiac regeneration through the use of various vertebrate species and pluripotent stem cell-derived NCCs. Here, we review the neural crest's regenerative capacity in various tissues and organs, and in particular, we summarize the characteristics of cardiac NCCs between species and their roles in cardiac regeneration. We further discuss emerging and future work to determine the potential contributions of NCCs for disease treatment.

Keywords: cardiac regeneration; heart structure; neural crest cells (NCCs); regeneration.

Figure 1

The ability of the cardiac neural crest (NC) to contribute to regeneration after cardiac injury in zebrafish and mammalian hearts. In the zebrafish, injured ventricular tissue has been shown to populate a large number of NC-positive cells that express high levels of sox10 and tfap2a that give rise to cardiomyocytes and myocardium of the regenerated ventricle. In the mammalian heart, the contribution of the NC to the ventricle and their ability to regenerate or maintain a stem cell-like state is still unknown. Although mammalian ventricular cardiac injury results in scarring and fibrosis with little-to-no regenerative ability, there is potential that the injured tissue releases the chemokine MCP-1, signaling to cardiac neural crest cells (NCCs) to migrate to the injury site to assist in tissue regeneration of the ventricle. (Created with Biorender, accessed on 29 November 2022).