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Updated: May 8, 2026
Real-Time Measurements of Calcium and Contractility Parameters in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes
Published on: May 26, 2023
Calcium signalling of human pluripotent stem cell-derived cardiomyocytes
Sen Li1, Gaopeng Chen, Ronald A Li
1R. A. Li: 5/F Hong Kong Jockey Club Building for Interdisciplinary Research, 5 Sassoon Road, Pokfulam, Hong Kong. ronaldli@hkucc.hku.hk.
Insights
Human pluripotent stem cells (hPSCs) can generate cardiomyocytes for heart repair. This review explores their immature calcium handling and maturation strategies for cell therapies.
Area of Science:
- Cardiovascular Biology
- Stem Cell Biology
- Regenerative Medicine
Background:
- Cardiomyocytes (CMs) have limited regenerative capacity, making loss irreversible and leading to heart failure.
- Human pluripotent stem cells (hPSCs) offer a renewable source of cardiomyocytes for therapeutic applications.
- Understanding hPSC-derived cardiomyocyte (hPSC-CM) function is crucial for effective cell-based therapies.
Purpose of the Study:
- To review the current understanding of calcium (Ca2+) handling in immature hPSC-CMs.
- To discuss the molecular basis of Ca2+ signaling in hPSC-CMs.
- To explore in vitro methods for promoting hPSC-CM maturation.
Main Methods:
- Literature review of studies on hPSC-CM calcium handling.
- Analysis of data on global Ca2+ transients and Ca2+ sparks in hPSC-CMs.
- Examination of molecular mechanisms underlying Ca2+ cycling in hPSC-CMs.
Main Results:
- hPSC-CMs exhibit immature Ca2+ handling properties compared to adult CMs.
- Specific molecular players and pathways influencing Ca2+ cycling in hPSC-CMs are being identified.
- Various in vitro strategies are being developed to enhance hPSC-CM maturation.
Conclusions:
- Immature Ca2+ handling is a key limitation in hPSC-CMs for therapeutic use.
- Targeting molecular pathways can drive hPSC-CM maturation.
- Further research into hPSC-CM maturation is essential for advancing cell-based cardiac repair.
Abstract:
Loss of cardiomyocytes (CMs), which lack the innate ability to regenerate, due to ageing or pathophysiological conditions (e.g. myocardial infarction or MI) is generally considered irreversible, and can lead to conditions from cardiac arrhythmias to heart failure. Human (h) pluripotent stem cells (PSCs), including embryonic stem cells (ESC) and induced pluripotent stem cells (iPSCs), can self-renew while maintaining their pluripotency to differentiate into all cell types, including CMs. Therefore, hPSCs provide a potential unlimited ex vivo source of human CMs for disease modelling, drug discovery, cardiotoxicity screening and cell-based heart therapies. As a fundamental property of working CMs, Ca(2+) signalling and its role in excitation-contraction coupling are well described. However, the biology of these processes in hPSC-CMs is just becoming understood. Here we review what is known about the immature Ca(2+)-handling properties of hPSC-CMs, at the levels of global transients and sparks, and the underlying molecular basis in relation to the development of various in vitro approaches to drive their maturation.
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