Versatile method produces massive numbers of authentic human heart muscle cells

Scientists at the Leiden University Medical Centre (LUMC) successfully cultured human heart muscle cells on a large scale. Because it is challenging to recreate heart muscle cells outside the body, this research is an exceptional achievement.

Why culturing human heart muscle cells strongly reduces animal testing

Video Credit: Leiden University.

The researchers, using an unique technique, developed a completely inexhaustible source of human heart muscle cells that would offer several new opportunities for research and studies related to heart diseases. The findings of this research were published in the journal Nature Biomedical Engineering.

Cardiac disorder atrial fibrillation is being investigated by Twan de Vries and his colleagues at the Department of Cardiology in LUMC. Laboratory animals are one of the tools they utilize.

This has many disadvantages. The use of laboratory animals is socially charged, animal care is expensive and the heart muscle cells of animals behave differently from human heart muscle cells in many respects.”

Twan de Vries, Department of Cardiology, Leiden University Medical Centre

Scientists usually prefer using human heart muscle cells. However, as these cells rarely multiply in the human body, let alone in a lab condition, they cannot get sufficient heart muscle cells for their research.

Switch

The researchers believed that the cells would rapidly multiply, by using an old trick of introducing an oncogene into the DNA of heart muscle cells. This approach worked well, but the cells lost their unique properties, like the capacity to contract, implying that they were not true heart muscle cells anymore.

Then I thought: what if we could turn the cancer gene off again.

Twan de Vries, Department of Cardiology, Leiden University Medical Centre

And that is exactly what happened. The first trial was successful with the oncogene that could be turned “on” and “off.”

By adding a substance to the cells, the oncogene becomes ‘active’. The heart muscle cells then lose their properties and start dividing rapidly. By removing the substance, the oncogene is turned off and the cells become beating heart muscle cells again.

Twan de Vries, Department of Cardiology, Leiden University Medical Centre

A virtually boundless source of human heart muscle cells has been provided by this method.

Less animals used for experiments

This discovery will pave way for better research into prospective new drugs for heart-related diseases, for they can be now tested on real human cells. In turn, this can make a vital contribution towards reducing animal testing. For the same reason, the study has been financially supported by the Dutch Society for the Replacement of Animal Testing.

More insight into heart diseases

The new method also allows scientists to find out accurately which genes influence specific features of heart muscle cells and which genes are responsible for the cell. In the future, this will help researchers to better understand how heart muscle cells function and how heart diseases, like atrial fibrillation, occur. This understanding can be used to formulate new methods for treating damaged hearts.

Source:
Journal reference:

Harlaar, N., et al. (2022) Conditional immortalization of human atrial myocytes for the generation of in vitro models of atrial fibrillation. Nature Biomedical Engineering. doi.org/10.1038/s41551-021-00827-5.

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