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October 2021

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Reversible reprogramming of cardiomyocytes to a fetal state drives heart regeneration in mice, DZHK authors: Eric Schoger, Laura C. Zelarayán, Johnny Kim, Thomas Braun, Science, 24 September 2021

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The human heart can only marginally heal itself when it is damaged. Because heart muscle cells hardly divide at all in a fully-grown organism. DZHK scientists from the Max Planck Institute for Heart and Lung Research in Bad Nauheim and an international team of researchers have reprogrammed heart muscle cells in mice to regenerate the damaged organ. However, the decisive factor is how long and how strongly the cells are reprogrammed: if this is not optimal, the heart does not recover, or tumours even form.

For their study, the team led by DZHK scientists Dr. Johnny Kim and Professor Thomas Braun introduced transgenic mice in which the expression of four stem cell factors in the heart can be switched on and off. The artificial expression of the factors reprogrammes the heart muscle cells to re-develop and divide again.

Initially, the scientists succeeded in activating the factors in isolated heart muscle cells from the transgenic mice. As a result, the cells gradually divided again. Many genes involved in cell division and metabolic control were also active in the mice after six weeks when the factors were switched on.

When factor expression was switched off again, the heart functioned unchanged. However, if the factors were active for a more extended period, the heart changed significantly and irreversibly, leading to impaired function. With permanent activation, the heart muscle cells even lost their original identity and heart tumours formed.
The researchers then examined whether the four stem cell factors can also trigger repair processes in the damaged heart. “In an infarct model, regeneration processes set in with factor expression turned on in a controlled manner. Compared to control animals, the infarct scar was significantly smaller, ”said Kim. Cardiac output also improved if the expression of the factors was switched on briefly before or shortly after a heart attack.

According to Braun, Director at the Max Planck Institute, the study demonstrates that the therapeutic restoration of organ functions in tissues with poor regenerative capacity can be successful if cells incapable of dividing are restored to their ability to divide.

Link to paper

Link to Press Release