Published online 23 April 2008 | Nature | doi:10.1038/news.2008.775

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Beating heart tissue grown in lab

Test-tube recipe produces three types of cardiac cell.

Heart cells, grown from scratch.Lei Yang

An international team of cell biologists has created heart tissue — complete with beat — in a test tube. The tissue culture contains three distinct cell types, each of which is important in functioning hearts, and is thus a step towards the advent of lab-grown heart-tissue transplants.

Researchers led by Gordon Keller of the McEwen Centre for Regenerative Medicine in Toronto, Canada, created the heart cells from human embryonic stem cells — cells found in developing embryos that have the potential to develop into any type of human tissue.

The team found that, by treating the embryonic stem cells with hormones called growth factors, they could encourage them to develop into a type of cell called cardiovascular progenitors. These cells, in turn, have the potential to become any of three specialized types of heart cell — two muscle cell types (cardiomyocytes and vascular smooth muscle) and endothelial cells, which form the lining of structures such as the heart's walls.

When these progenitor cells were grown in a dish, they developed their own intrinsic 'heartbeat' — one of the key characteristics of heart tissue — the researchers report online in Nature1.

What's more, when Keller and his colleagues transplanted a mixture of the three cell types into the hearts of mice with simulated heart disease, their heart function improved significantly, although the researchers don't know whether the improvement would be sustained throughout life.

Mend a broken heart

"This is exactly what you would like to transplant into a heart," says heart physiologist Bernd Fleischmann of the University of Bonn, Germany. Although not yet tested in humans, the technique could offer a useful way to patch up heart muscle damaged by a heart attack.

However, absent from the mix is another type of cell called fibroblasts, which provide structural support for heart tissue, Fleischmann points out. "I am not sure whether these [cardiovascular progenitor] cells could also form fibroblasts," he says.

But fibroblasts may not even be necessary, says Keller. Three-dimensional cardiac grafts could potentially be grown on artificial structures instead, he says.

Researchers would also like to see the test done on a wider range of embryonic stem cell lines, to ensure that the trick is possible with any given embryonic stem cell.

Last year, Fleischmann's research team successfully repaired mouse hearts using muscle progenitor cells taken from mice embryos and nurtured to become implantable heart tissue (see 'Cells mend damaged mouse hearts'). The new treatment uses cells taken from an even earlier point in development, which are easier to obtain.

Patient matched

The next step, Fleischmann predicts, will be to develop similar treatments using patients' own cells. But this requires cell biologists to master a way of creating patient-matched embryonic stem cells, either through cloning, or by reprogramming adult cells into 'induced pluripotent' cells.

If the latter can be mastered, it would allow patients with heart disease to be given patches of new heart cells grown from their own adult cells, without using an embryo.

But it is hard to know if such a procedure can be made effective and safe. "That's the million-dollar question," says Chris Denning, who studies iPS cells and heart development at the University of Nottingham, UK. But he remains confident. "It will take time, but I think this problem will get cracked."

Keller's group is also pursuing the option of induced pluripotent cells. "That will be the next thing we'll go for aggressively," he says. 

Watch videos of the heart cells in action: video1, video2, video3.

  • References

    1. Yang, L. et al. Nature doi:10.1038/nature06894 (2008).
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