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Thursday, Aug. 9, 2001

NATURAL SELECTIONS

Wolverine mouse regenerates heart tissue


In the movie "X-Men," humans with genetic mutations displayed supernatural powers: telepathy, weather control, telekinesis, the ability to create magnetic fields, etc. All clearly sci-fi, comic-book stuff, above nature . . . or was it?

The "X-Men" character Wolverine is able to regenerate damaged tissue after injury, an ability seen in certain reptiles and amphibians that replace lost limbs, tails and other tissues. For centuries, doctors and surgeons have dreamed of a way of inducing regeneration in humans, but, alas, tissue regeneration does not occur in mammals -- wounds are just patched up and healed with scar tissue.

At least, it was not thought to occur in mammals. That was until Tuesday, when a landmark paper was published in the Proceedings of the National Academy of Sciences.

In the paper, scientists at The Wistar Institute, Philadelphia, describe how a strain of laboratory mice regenerated seriously damaged heart tissue, without scarring. Remarkably, the mouse strain, known as MRL mice, repaired their injuries without drugs, infusions of cells (such as stem cells), or any other kind of intervention. The mice are not genetically modified organisms -- the regenerative ability is an innate, native capacity of this strain of mouse.

In the tradition of great scientific discoveries, Ellen Heber-Katz, the senior author of the paper, discovered the extraordinary powers of the strain entirely by accident. Lab mice are identified by labels attached to their ears, and one day Heber-Katz noticed that the MRL mice had healed the small puncture wounds caused by the labels. Amazingly, the wounds showed no signs of scarring.

Heber-Katz and coworkers traced the complex regenerative ability to multiple locations on five chromosomes. They then built on their findings, and tested if the regenerative abilities extended to cardiac damage. To do so, the researchers induced cryogenic damage to the right ventricle of mice hearts. In living mice they created a sublethal infarction -- an area of dead tissue in the heart -- by killing the cells with a cold probe. Then they studied how it healed.

Sixty days after the injury, the wounds had healed and heart function was normal. In control mice of a different strain, only 1 to 3 percent of the wounded cells had regenerated.

Among vertebrates, regeneration to this extent has previously only been seen in urodeles -- a group that includes newts and salamanders. These animals are able to regenerate legs and tails, as well as heart muscle, jaws and even spinal cord.

They do this by a process called dedifferentiation. At the site of a wound -- say a severed leg -- blood, skin, bone and nerve cells lose their identity. They regress -- dedifferentiate -- back to the most basic, unspecialized cell type. The cell mass then grows into a limb bud, and as the new leg grows, the cells take on new, specialized roles. But regeneration in mammals?

"In more than 15 years of investigations involving muscle tissue I'd never seen anything like this," said John Leferovich, the first author of the paper. "The observation was quite stunning."

The researchers are now attempting to identify the genetic and molecular differences between the MRL mice and other strains. "Candidate genes include proteases and molecules like collagen involved in scarring," said Heber-Katz.

The researchers believe that the MRL mice have somehow overcome the patch-up and scar restrictions of normal mammalian healing. Minimal regeneration is seen in mammals and has been documented in a human cadaver, but something stops it progressing. "Mammals in general have the potential to regenerate," said Heber-Katz.

Ultimately the research could lead to radical new drugs that would speed up healing of a broad array of injuries and diseases. And the centuries-old dream of surgeons?

"We believe that functional tissue regeneration will be achieved in humans and that this will happen in a relatively short period of time -- maybe within the next five years," said Heber-Katz.

Tissue regeneration would herald a new era of medicine -- but don't expect to see any real-life Wolverines just yet.

Readers can contact Rowan Hooper at rowan@japantimes.co.jp Natural Selections is taking a two-week summer break and will return Aug. 30.


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