Stem cells and regeneration signals from cells help regrow amputated digits in mice

Scientists have long known that children and some adults can regrow the tips of their fingers and toes after amputation. But digits can’t regenerate if more than the nail region is amputated.

The digit bones can regenerate only if the amputated stump still has some nail stem cells, the researchers found. But the cells alone are not enough; also crucial is a zone of tissue that grows from the stem cells during normal nail growth. After amputation, this tissue sends signals that attract new nerves into the end of the stump and begin the bone regeneration process. If amputation removes the nail zone or if the signals are blocked, the digits will not regenerate.

When the researchers genetically manipulated the mice to turn on the regeneration signals permanently, nail stem cells alone could spur digit regeneration even without the neighboring nail tissue zone.

A mouse toe tip five weeks after amputation looks like new (top). But when signals from the nail tissue are blocked, the nail and digit can’t regrow (bottom). Muscles and nail keratin are stained red in the image and collagen is green or blue. Takeo et al/Nature 2013

Other researchers have found that similar signals are involved in regenerating amputated amphibian limbs. “We were really amazed by the similarity between these processes,” Ito says. The parallels suggest that mammals might retain some of the newt’s famous power to regrow entire legs.

The similarity between mammalian and amphibian regeneration is encouraging, says Ken Muneoka of Tulane University. That parallel, he says, “gives us hope that we will be able to induce human regeneration in the not too distant future.”

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