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Mice Regrow Heart Muscle

Curious research finds mutant strain can regenerate without scarring

MONDAY, Aug. 6, 2001 (HealthDayNews) -- Lizards regenerate themselves, but mammals aren't supposed to. Apparently, at least one strain of mice hasn't heard that rule.

New research shows that after a normally irreversible infarction, so-called MRL mice can regenerate their heart muscle -- without the aid of drugs, cell therapy or other interventions.

For now, the finding is a curiosity and a marvel. Yet it could one day help people who've suffered heart attacks repair the damaged pump or speed healing in other wound patients. The findings appear in the latest issue of the Proceedings of the National Academy of Sciences.

Unlike reptiles and amphibians, mammals are notoriously poor at regenerating lost or damaged body parts, with a few notable exceptions such as the liver. In the case of the heart, the conventional wisdom, until only recently, said that no remodeling goes on at all once cardiac muscle dies: Where others repair, we scar.

New research has shown that that's not entirely true -- human heart muscle can return after an attack, though probably not enough to make much clinical difference.

MRL mice, however, are a different tale entirely. This strain has a set of spontaneous genetic "errors" that give it extraordinary self-healing powers, in the form of proteins that promote wound repair.

Earlier work, for example, showed that MRL mice can pave over punched-out holes in their ears with normal tissue structure and even effect cartilage replacement, which is "almost unheard of," says Ellen Heber-Katz, who discovered the phenomenon.

In the latest study, Heber-Katz, an immunologist at the Wistar Institute, and her colleagues there and at Thomas Jefferson University used an ultra-cold probe to damage the hearts of mice and cause infarctions, or loss of blood, to the organ's right ventricle.

Normal mice suffered severe damage, and subsequent tests showed rampant scarring and only random scatterings of new muscle cells in the region.

But within a week of the infarction, the MRL mice developed "fingers" of new tissue that began to spread across the injury. Within two weeks, the heart lining had essentially returned to normal function. They were almost free of scar tissue, and their heart muscle cell, or cardiomyocyte, proliferated as much as 10 times faster than the other test rodents.

"Functionally the tissue is normal. It looks normal," Heber-Katz says.

The researchers say the extraordinary healing powers of the MRL mice are probably the result of their ability to prevent scarring at its most fundamental levels of enzyme and protein activity. "We think that it is the breakdown of scar tissue that allows the [healthy] growth to occur," Heber-Katz says. Understanding this talent, in turn, could help scientists come up with treatments for people who've suffered tissue death or damage, she says.

Godfred Masinde, a research scientist at the Jerry L. Pettis VA Medical Center in Loma Linda, Calif., who has replicated Heber-Katz's work in MRL mouse ears, says finding the genes for wound healing could be a major advance for surgery.

Healing without a scar might be possible, he says -- either through gene therapy or, if humans have dormant versions of the MRL mouse instructions, by flipping the right genetic switch. "Plastic surgeons might have less to do," Masinde says.

What To Do

To find out more about MRL mice, try this site with some of Heber-Katz's work. For more on tissue regeneration, check out the University of California at Davis.

SOURCES: Interviews with Ellen Heber-Katz, Ph.D., professor of immunology, Wistar Institute, Philadelphia; Godfred Masinde, Ph.D., research scientist, Jerry L. Pettis V A Medical Center, Loma Linda, Calif.; Aug. 14, 2001, Proceedings of the National Academy of Sciences
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