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Cells with two nuclei could be key in the regeneration of the heart

Cells with two nuclei could be key in the regeneration of the heart

A research team led by IBEC, in collaboration with CMR[B], discovers a mechanism that generates cells with two nuclei

This mechanism has been identified during the regeneration of the heart of zebrafish and could be associated with the extraordinary regenerative power of this animal

After an acute injury, such as a myocardial infarction, the human heart is unable to regenerate. Adult cardiac cells cannot grow and divide to replace the damaged, and the injury becomes irreversible. But that does not happen in all animals. A freshwater fish from Southeast Asia, known as zebrafish, can completely regenerate your heart even after 20% amputee of your ventricle.

This extraordinary regenerative capacity has attracted the attention of researchers around the world, who see the range of possibilities that would open if this mechanism of regeneration could be applied in human-oriented therapies.

In an article published today in the journal Nature Materials, a team of researchers from the Institute of Bioengineering of Catalonia (IBEC) led by Xavier Trepat, in collaboration with the Center of Regenerative Medicine of Barcelona (CMR [B]), have discovered an amazing mechanism by which the zebrafish cardiac cells move and divide during regeneration.

The researchers have focused on the epicardium, which is the layer of cells that covers the heart. Although the epicardial cells represent only a small fraction of the mass of the heart, they play a fundamental role in their regeneration. "Epicardium is the origin of several cellular types of the heart, and secretes biochemical signals that indicate to the rest of the cells what they must do at all times. It's kind of a 'hub' of regeneration", says Ángel Raya, ICREA Researcher and director of the CMR[B].

After an injury, epicardium cells begin to divide and move in mass to cover the wound. Researchers have observed that during this process the cells become bi-nucleated: they duplicate the genetic material and separate it into two nuclei, but they cannot be divided into two independent cells. "We were very surprised to discover cells that instead of having a nucleus, as usual in most tissues, have two, and each of them contains a copy of the DNA of the cell," says Trepat, ICREA researcher at IBEC and associate professor at the University of Barcelona.

The researchers have discovered that the mechanism by which the cells become bi-nucleated is of biomechanic origin. Once the DNA has already been separated into two nuclei, most animal cells form a contractile ring on its equator. As it goes away, this ring divides the stem cell into two daughter cells. In the case of zebrafish heart cells, the study shows that the ring adheres to the fibers in its surroundings so that it cannot contract. The result is that the two daughter cells cannot get separated despite having successfully duplicated their DNA.

"Multinucleation is a well-known phenomenon in cancer, because it is a cause of genomic instability. That is, cancer cells lose control of the proteins they synthesize and behave pathologically. In the case of the zebra fish heart, multinucleation is physiological and does not seem to cause any problem, "says Marina Uroz, the first author of the article. The next step is to study the role of multi-nucleated cells during the regeneration of the heart and other organs.

Dr. Trepat and Dr. Raya are part of the CIBER-BBN (Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina).

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Traction forces at the cytokinetic ring regulate cell division and polyploidy in the migrating zebrafish epicardium

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