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Review
. 2025 Mar;603(7):1865-1885.
doi: 10.1113/JP286416. Epub 2024 Sep 5.

Modelling neurocardiac physiology and diseases using human pluripotent stem cells: current progress and future prospects

Hsueh-Fu Wu  1   2 , Charlotte Hamilton  3 , Harrison Porritt  3   4   5 , Annika Winbo  3   6 , Nadja Zeltner  1   2   7
Affiliations
Review

Modelling neurocardiac physiology and diseases using human pluripotent stem cells: current progress and future prospects

Hsueh-Fu Wu et al. J Physiol. 2025 Mar.

Abstract

Throughout our lifetime the heart executes cycles of contraction and relaxation to meet the body's ever-changing metabolic needs. This vital function is continuously regulated by the autonomic nervous system. Cardiovascular dysfunction and autonomic dysregulation are also closely associated; however, the degrees of cause and effect are not always readily discernible. Thus, to better understand cardiovascular disorders, it is crucial to develop model systems that can be used to study the neurocardiac interaction in healthy and diseased states. Human pluripotent stem cell (hiPSC) technology offers a unique human-based modelling system that allows for studies of disease effects on the cells of the heart and autonomic neurons as well as of their interaction. In this review, we summarize current understanding of the embryonic development of the autonomic, cardiac and neurocardiac systems, their regulation, as well as recent progress of in vitro modelling systems based on hiPSCs. We further discuss the advantages and limitations of hiPSC-based models in neurocardiac research.

Keywords: autonomic nervous system; cardiology; disease modelling; human pluripotent stem cell; neurocardiology.

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Conflict of interest statement

All authors declare that there are no competing interests.

Figures

Figure 1
Figure 1. Efferent neurocardiac system
Simplified anatomy and physiology of the efferent neurocardiac system.
See this image and copyright information in PMC

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