Zebrafish extract heals a broken heart

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A coloured scan of a zebrafish (Danio rerio) head with the ventricle and ventricular cavity of its heart shown in red in the lower right. The molecules around its cardiac cells, when injected into a mouse with a damaged heart, can help repair cardiac tissue.

The unassuming zebrafish is a pretty radical animal. The little fish can stitch its severed spine together again – and now, biologists from the US and Taiwan have shown the substance surrounding its heart cells can patch up an injured mouse heart.

William Chen from the University of Pittsburgh and colleagues injected zebrafish extracellular matrix – the stuff that supports cells – into mice with damaged cardiac tissue. The treatment enhanced cardiac cell replication and tissue regeneration, and improved heart function overall.

The work, published in Science Advances, even pinpoints the proteins that play significant roles in the transformation.

Heart disease is the leading cause of death in men and women. Every year, around 730,000 Americans have a heart attack, where a blocked artery deprives part of your heart of blood – and thus oxygen and fuel.

The longer the blockage lasts, the more cells start dying. If blood flow isn’t regained quickly, damage to the heart muscle is permanent.

Some groups are looking at techniques such as stem cell implants to help repair this damage.

How some animals regenerate damaged body parts – even entire limbs – is of great interest to researchers wishing to fix injured heart tissue.

The zebrafish has amazing powers of regeneration, including the ability to patch up its heart. Could the stuff that supports its own heart cells be useful in other species – even mammals?

Chen and colleagues took zebrafish hearts and removed the cells so they were left with only the extracellular matrix. They ground it into a powder and injected it into mice with induced heart damage, like that seen in a heart attack.

To control, they also extracted mouse extracellular matrix and injected that into another set of mice.

The mice that received a single dose of zebrafish powder made a remarkable recovery, with their heart cells repopulating and replenishing the injured regions and beating again.

Those that were given the mouse extracellular matrix, though, didn’t see these benefits.

Chen and his crew also wondered if the zebrafish powder might help human heart cells. They couldn’t very well inject it into a real heart attack patient, though, so they grew human heart cells in the lab.

They starved the cells of nutrients and oxygen – emulating the conditions of a heart attack – then added the zebrafish powder. Sure enough, the cells proliferated.

The components at least partly responsible for the zebrafish powder’s power, the researchers write, are proteins neuregulin-1 and ErbB2. They regulate cell division and so play significant roles in the regeneration. Actively healing zebrafish hearts produces lots of neuregulin-1.

And when ErbB2 signalling was blocked, Chen and his colleagues found zebrafish extracellular matrix powder didn’t help a damaged mouse heart recover.

As a next step, the authors are exploring the effect of less invasive zebrafish extracellular matrix treatment on larger animal models of heart attack.

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