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Scavenger cells help limbs to regrow

Limb regrowth An immune system cell that helps limbs regrow in salamanders brings hope that we may eventually be able to mimic the animal's amazing regenerative powers, say Australian researchers.

The findings by Dr James Godwin, of the Australian Regenerative Medicine Institute at Monash University, and colleagues, are published in today's issue of the Proceedings of the National Academy of Sciences.

Salamanders (axolotls) are unique amongst vertebrates in being able to repair their hearts, tails, spinal cord and brain, and even regrow whole limbs during adult life, says Godwin.

He sees their "perfect regeneration" as a holy grail. "We're trying to work out what the requirements are so we can unlock that potential in mammals," he says.

Not just gobblers

He has suspected for a while that macrophages, cells involved in the immune system, might be important in the regeneration process.

Macrophages are a major immune cell type which roam the tissues engulfing invaders like bacteria and fungi, explains Godwin.

"But they're not just involved in gobbling up debris. They actively determine repair - for example they are important in human muscle repair," he adds.

"So we asked the question - are macrophages needed for limb regeneration?," he says.

When the team got rid of the macrophages in the salamanders, it had a "devastating effect" on their ability to regrow limbs. The animals ended up with fibrosis (scarring) and a stump.

Godwin believes that chemicals released by the animals' macrophages are essential for the regeneration process, and is conducting experiments now to investigate this.

"This really gives us somewhere to look for what might be secreted into the wound environment that allows for regeneration," he says.

"The long-term plan is that we'll know exactly what cocktail to add to a wound site to allow salamander-like regeneration under hospital conditions."

Scar-less healing

Commenting on the study, Dr Andràs Simon of the Karolinska Institute in Sweden says "There has been a lot of discussion about how cells of the immune system might impinge on the regenerative process.

"No one has experimentally addressed this before, so in that sense it's very important."

He says the work has implications not just for entire limb regrowth, but for "smaller, less ambitious" goals such as scar-less healing.

Although scars perform a useful function in stopping blood loss and preventing infection getting into a wound, they inhibit communication between cells and this prevents regeneration, says Simon.

Down the track, using the salamander's approach could maybe help with healing of burns, for instance, he suggests.

Lost in the lottery?

But why has evolution lost such a seemingly useful capacity as the ability to regrow a whole limb?

Godwin says he is speculating, but formation of scars to prevent blood loss and infection may have been vital for mammals which are constantly on the move.

Or we could have just been unlucky in the "evolutionary lottery" he says. "Sometimes things just get lost."