Heart In A Dish: How IPSCs Transformed Cardiac Research

By Asst Prof Chrishan Ramachandra, Principal Investigator, NHRIS

In 2006, Japanese scientist Shinya Yamanaka made a landmark discovery when he showed that an ordinary adult skin cell could be reprogrammed into an infancy-like state, known as induced pluripotent stem cells, or iPSCs¹. Unlike ordinary adult cells that are locked into a fixed role, iPSCs can be turned into many different cell types and tissues, from heart muscle to nerve cells — cell types that are otherwise difficult to obtain from living people for research and clinical purposes (Fig. 1). This makes iPSCs a valuable source of human cells for scientists and clinicians alike. Given their human origin, one of the first hopes for iPSCs was cell therapy, where the idea was to convert iPSCs into a specific cell type, such as heart cells, and transplant them into damaged organs in the hope of repairing or regenerating the tissue. Over time, however, the most promising use of iPSCs has turned out to be disease modelling and drug discovery.

From Patient to Petri Dish

Disease modelling means using iPSCs to mimic a patient's disease in a dish, quite literally, a heart in a dish. As iPSCs can be made from a patient's own cells, they carry that person's genetic information, including any changes that may increase disease risk. This allows researchers to study what may be going wrong in the heart from a new perspective, beyond what can be observed through conventional clinical assessment. By understanding the mechanisms that cause disease, researchers can also begin to look for new treatments, including approaches tailored to individual patients, also known as precision medicine. In the early days, however, making heart cells from iPSCs was a major challenge, because researchers did not yet fully understand the signals needed to guide this transformation. Gradually, by learning from how the heart develops in the embryo, researchers were able to improve these techniques and produce enough heart cells for research purposes². This step was especially important because heart cells are unique, and unlike many other cell types, they must work continuously throughout life, beating without rest. As a result, they have specialised structural, functional, metabolic, and electrical features that are essential for the heart to do its job, and these features also need to be reflected when making heart cells from iPSCs³.

Figure 1: iPSC generation workflow. Patients with heart disease provide blood for reprogramming into iPSCs. These iPSCs can be transformed into specific cell types for various research and clinical applications.

Researchers at the National Heart Research Institute Singapore (NHRIS) have established an iPSC-based human cell platform in which iPSCs are generated from patients' blood rather than skin cells, as blood collection is less invasive. These iPSCs have been derived from patients with various heart diseases and used to model conditions such as channelopathies, which affect heart rhythm, cardiomyopathies, which affect heart structure, and heart failure, which affects the heart's pumping function. In addition to reproducing disease features in the dish, researchers have also identified novel therapies for these conditions⁴˒⁵. Furthermore, as some diseases are driven by genetics, iPSCs have also been used to confirm whether certain genes truly cause disease, which can help clinicians better understand and manage their patients.

A Human-First Future for Drug Discovery

While these findings are exciting, they were carried out using single-layer heart cells. This led to an important question: do these cells truly reflect the complexity of the human heart? After all, the heart is not just a flat layer of beating cells, but rather, a three-dimensional (3D) organ made up of heart cells, blood vessels, and supporting cells that all work together. For this reason, there has been major growth in organoid research over the past few years. Organoids are small, lab-grown mini organs made from multiple cell types, and researchers are now creating more advanced heart models to better mimic the human heart (Fig. 2). Heart organoids allow for tissue-like organisation and cell-cell interaction, enabling insights into how these different cell types communicate and function as a coherent unit rather than in isolation. Whether these organoids will reveal new insights into disease is something that the field is still actively exploring.

Figure 2: Microscopy images of single-layer heart cells (left) and 3D multi-cellular heart organoids (right) produced at NHRIS. In the organoids, red and green dyes stain heart muscle and blood vessels, respectively.

One of the biggest challenges in drug development is that more than 90% of drugs that appear safe in animal studies ultimately fail in human clinical trials. In April 2025, the US Food and Drug Administration (FDA) announced its Roadmap to Reducing Animal Testing in Preclinical Safety Studies, with the goal of incorporating New Approach Methodologies (NAMs) into drug development. NAMs include human cell- and organoid-based systems, including iPSC-derived models, and may improve predictions of drug efficacy and safety, thereby accelerating the translation of new therapies. These human-relevant systems are important because they may better reflect how the human heart responds to disease and treatment, helping researchers identify promising therapies earlier and reduce the chance of failure later in clinical trials. This shift places NHRIS's human cell platform at the forefront of modern drug discovery and has also encouraged closer engagement with pharmaceutical companies.

Twenty years after its discovery, iPSC technology has become a cornerstone of modern biomedical research. What began as a breakthrough in cell reprogramming has become a powerful platform for understanding disease, advancing precision medicine, and supporting safer drug development. As NHRIS continues to advance its human cell platform, the next chapter of iPSC research promises to bring even greater understanding of heart disease — and, ultimately, better outcomes for patients.

References

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