Gene discovery could help amputees grow new limbs

Posted by Emma Woollacott

Humans and other mammals could regrow lost limbs, following the identification of a gene that appears to regulate regeneration.

While creatures like flatworms, sponges, and some species of salamander have this ability, it has been long lost in mammals.

But researchers from the Wistar Institude have identified a gene, p21, that when removed from mice gives them the ability to regenerate lost or damaged tissue.

Mammals usually heal wounds by forming a scar. But these mice begin by forming a blastema, a structure seen in amphibians and associated with rapid cell growth and de-differentiation.

According to the Wistar researchers, the loss of p21 causes the cells of these mice to behave more like embryonic stem cells than adult mammalian cells.

"Much like a newt that has lost a limb, these mice will replace missing or damaged tissue with healthy tissue that lacks any sign of scarring," said the project’s lead scientist Ellen Heber-Katz.

"While we are just beginning to understand the repercussions of these findings, perhaps, one day we’ll be able to accelerate healing in humans by temporarily inactivating the p21 gene."

The discovery came about quite by chance, when Heber-Katz realised that holes in the ears of a particular strain of mice, MRL mice, had healed up. The holes were intended as an identification marker, and that particular experiment was ruined.

But the researchers wondered how it had happened, and started to focus on mapping the critical genes that turn MRL mice into healers.

Meanwhile, cellular studies at Wistar revealed that MRL cells behaved very differently to cells from other mouse strains in culture.

The team found that p21, a cell cycle regulator, was consistently inactive in cells from the MRL mouse ear. It turned out that p21 knockout mice had already been created, and indeed were widely used in many studies. What nobody had noticed was that these mice could heal their ears.

"In normal cells, p21 acts like a brake to block cell cycle progression in the event of DNA damage, preventing the cells from dividing and potentially becoming cancerous,” Heber-Katz said. "In these mice without p21, we do see the expected increase in DNA damage, but surprisingly no increase in cancer has been reported."