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Friday, 13 December, 2002, 00:30 GMT
Zebrafish hold clue to mending hearts
Pic: Wellcome Institute
Zebrafish have regenerative powers
A tropical fish's ability to "grow a new heart" may help scientists find a way of aiding the recovery of human patients.

The zebrafish is one of the only vertebrates whose heart can recover in this way, even when a fifth of the organ's tissue is removed.

In humans, even minor damage to the heart leaves a trail of scar tissue which makes full recovery difficult.

Experts from the US hope that the secrets of the zebrafish's scar-free regeneration could be harnessed in human patients.

They have found a gene in the zebrafish which appears to play a role in this remarkable healing process.

Dr Mark Keating from the Howard Hughes Medical Institute led a team that removed 20% of the two-chambered heart in dozens of zebrafish.

The zebrafish could take this field of research out of the Dark Ages

Dr Mark Keating, Howard Hughes Medical Institute
While one-fifth of the fish did not survive this initial trauma, the rest set about curing the problem.

A clot of red blood cells formed around the wound, and over the next week the clot hardened in a similar way to human wound healing.

However, after seven days, the clot tissue, which in humans remains to form scar tissue, was gradually replaced by new muscle fibres.

Chemical markers placed in certain cells revealed that a new heart wall formed and expanded rapidly upwards to reproduce the original shape of the organ.

Two months after the wound was created, the hearts of these fish had completely recovered.

Cell supply

Unlike humans, the cells nearest the injury "de-differentiated" - they took a developmental step backwards and regained the ability to be converted into various types of specialised heart cells, thus providing the raw materials for the repair of the heart.

While many invertebrate creatures are capable of replacing damaged organs, the zebrafish is unusual as a vertebrate with this ability.

Scientists believe that the scarring which characterises human tissue repair is still going on, but is "overwhelmed" by energetic production of new muscle fibres.

When this ability was damped down by removing a key muscle production gene from the fish, they produced scars at the wound site instead.

In humans, the researchers speculated, it might simply be that the balance between these two abilities is weighted more firmly towards scarring in humans.

Dr Keating said that beefing up the regenerative ability in humans might allow it to compete more effectively against the scarring mechanism - and perhaps allow a more complete recovery from heart attack damage.

He said: "The zebrafish could take this field of research out of the Dark Ages.

"If one enhances the regenerative potential in humans, perhaps one can overcome the fibrotic [scarring] potential."

Belinda Linden, Head of Medical Information at the British Heart Foundation, told BBC News Online:

"Research into a range of life forms has resulted in many discoveries over recent years.

"Although the zebrafish's heart has characteristics that are far removed from the human heart, this research offers insight into the potential benefits of gene therapy."

The research was published in the journal Science.

A similar principle has been employed by British doctors, who have injected bone marrow stem cells into damaged hearts, in the hope that they will be converted into fresh muscle cells by contact with the damaged area.

The BBC's Nick Adcock
"Within two months of surgery, the fish were back to normal"
See also:

14 Jun 01 | Science/Nature
21 Nov 00 | Science/Nature
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