Diseased foetal heart can regenerate itself

London, Oct 16 : If the heart becomes diseased during its embryonic development, it can regenerate itself to such an extent that it is fully functional by birth, provided some of the heart cells remain healthy.

Jorg-Detlef Drenckhahn of the Max Delbrück Centre for Molecular Medicine (MDC) Berlin-Buch made this discovery together with colleagues from Australia.

They were able to demonstrate in female mice that the healthy cells of the heart divide more frequently and thus displace the damaged tissue.

"Hopefully, our results will lead to new therapies in the future," Drenckhahn said. "With the right signals, a heart that has been damaged might be stimulated to heal itself."

For the heart to be able to beat, it needs energy. If the energy production in the heart cells is disturbed, then the embryo will actually die of heart dysfunction.

But if only a portion of the cells is affected, this is not the case: With the aid of the remaining healthy cells, the embryo manages to regenerate the heart, according to a MDC press release.

The scientists switched off a gene (Holocytochrome C synthase, or Hccs) in the developing hearts of mice - a gene that is essential for energy production.

Results showed that the embryos died when all cells in the heart were affected by the defective energy production. However, the animals that still had some healthy myocardial cells survived, and at the time of birth they had a heart that was fully able to function.

The gene Hccs is located on one of the sex chromosomes, the X chromosome. In contrast to male animals who have only one X chromosome, females have two X chromosomes.

Some of the altered female mice have an X chromosome with the defective Hccs gene and one with the intact Hccs gene. However, in the cells of the female animals, only one X chromosome is active.

Depending on which one is expressed, either healthy or diseased heart cells develop. "At this point in time, the heart of the mice is like a mosaic," Drenckhahn said. "Half of the cells are healthy, the other half not."

Up until birth, the foetal heart manages to improve the ratio of healthy cells to defective cells from the original 50:50 ratio. The defective cells then only comprise 10 percent of the entire heart volume.

That is possible because the healthy myocardial cells divide much more frequently than the defective cells. Their percentage in the heart increases so that, at the time of birth, the ratio is large enough to allow the heart of the newborn mouse to beat normally. "But even for a while after birth, the heart is capable of compensatory growth of healthy cardiac cells," Drenckhahn explained.