Regeneration of Mammalian Cardiomyocytes Demonstrate

Unlike normal mammalian cardiac tissue, the hearts of the MRL mouse strain can regenerate cardiomyocytes following infarction, with full recovery of myocardial function, the Wistar Institute in Philadelphia announced Monday.

Dr. Ellen Heber-Katz and associates had previously shown this mouse strain to be unique in its capacity for regenerative wound healing (see Reuters Health report, February 18, 1998). They found that at least six loci on five chromosomes are associated with the regenerative capability.

According to their current report, to be released online Tuesday by the Proceedings of the National Academy of Sciences, the investigators induced cardiac infarction in the right ventricle of control and MRL mice using a cold probe.

“At day 5 there was an inflammatory response and infiltrate, but after that the [MRL] animals just got better,” Dr. Heber-Katz told Reuters Health.

At 2 months, microscopic examination revealed “totally normal appearing tissue” in some of the animals, she said, while in others, “we could tell they had been injured, because there was a little bit of scar tissue on top and around the edges” of the infarction.

“I believe these animals have the ability to break down scars very easily, or else they control the material being laid down and how rapidly it accumulates,” she said.

The only other organisms capable of cardiac regeneration are certain reptiles and amphibians, the investigators note in their paper. Dual staining of nuclei showed the mitotic index of MRL mouse tissue to be in the neighborhood of 10% to 20%, they report, similar to that seen in frogs and lizards after ventricular injury.

Dr. Heber-Katz believes that differing levels or types of collagen, or a different mechanism of collagen breakdown, may explain the findings. She predicts that when further research precisely elucidates the mechanism and its time course, similar recovery will be possible in humans.

Since the time that Dr. Heber-Katz and her associates submitted the article for publication, she said, they have successfully grown cardiomyocytes from both control mice and MRL mice in culture. “Both seem capable of dividing,” she said, “which is consistent with the idea that it’s just the scar tissue that normally prevents cardiac regeneration after injury.”

Proc Natl Acad Sci USA 2001;98:9830-9835.