In the cardiomyocytes of humans and other mammals, centrosome integrity is lost soon after birth, impairing the heart’s ability to regenerate. Restoring centrosome integrity in heart cells might improve recovery from heart attacks. Also, disrupting centrosome integrity might slow the proliferation of cancer cells. [iStock/© akindo]
In the cardiomyocytes of humans and other mammals, centrosome integrity is lost soon after birth, impairing the heart’s ability to regenerate. Restoring centrosome integrity in heart cells might improve recovery from heart attacks. Also, disrupting centrosome integrity might slow the proliferation of cancer cells. [iStock/© akindo]

In humans and other mammals, cardiac muscle cells stop replicating soon after birth, unlike the cardiac muscle cells in, say, zebrafish and amphibians. What do zebrafish and amphibian cardiomyocytes have that our cardiomyocytes lack? Intact centrosomes, it turns out.

According to scientists at the University of Erlangen-Nuremberg, centrosome integrity is carefully regulated. If chromosome integrity in humans could be manipulated, these scientists suggest, the regenerative capacities of cardiac cells could be reawakened, enabling new medical treatments, hastening recovery from heart attacks, for example. Also, it might be possible to impair the centrosome integrity of wildly reproducing cells—cancer cells—to prevent them from spreading.

The University of Erlangen-Nuremberg scientists, led by David Zebrowski, Ph.D., and Felix B. Engel, Ph.D., presented their work August 6 in the journal eLife, in an article entitled, “Developmental alterations in centrosome integrity contribute to the post-mitotic state of mammalian cardiomyocytes.”

“[Loss of mammalian centrosome integrity] is coupled with relocalization of various centrosome proteins to the nuclear envelope,” wrote the article’s authors. “Consequently, postnatal cardiomyocytes are unable to undergo ciliogenesis and the nuclear envelope adopts the function as cellular microtubule organizing center. Loss of centrosome integrity is associated with, and can promote, cardiomyocyte G0/G1 cell cycle arrest suggesting that centrosome disassembly is developmentally utilized to achieve the post-mitotic state in mammalian cardiomyocytes.”

Essentially, the centrosome in mammalian cardiac muscle cells undergoes a process of disassembly which is completed shortly after birth. “This disassembly process proceeds by some proteins leaving the centrosome and relocating to the membrane of the cell nucleus in which the DNA is stored,” explained Prof. Engle. “This process causes the centrosome to break down into the two centrioles of which it is composed, and this causes the cell to lose its ability to reproduce.”

The scientists also established that unlike mammalian cardiomyocytes, the cardiomyocytes of adult zebrafish and newt maintain centrosome integrity, and never lose the ability to proliferate.
“We were incredibly surprised to discover that the centrosome in the cardiac muscle cells of zebrafish and amphibians remains intact into adulthood,” noted Dr. Zebrowski. “For the first time, we have discovered a significant difference between the cardiac muscle cells of mammals and those of zebrafish and amphibians that presents a possible explanation as to why the human heart cannot regenerate.”

The discovery that there is a natural process that regulates centrosome integrity in the cardiac muscle cells of mammals opens up a range of possibilities for future research. Firstly, this observation provides a new starting point for attempts to stimulate the reproduction of cardiac muscle cells in humans to regenerate the heart. At the same time, centrosome integrity can be examined in order to find adult cardiac muscle cells that may have retained their ability to reproduce, which may enable new forms of medical treatment. Finally, a detailed understanding of the mechanism could also help researchers to develop methods of inhibiting the uncontrolled growth of cancer cells.