Scientists Regrow Amputated Toes in Mice. Could the Same Process Work in Humans?

Two growth factors pushed scar-prone wounds toward imperfect but surprising regeneration.

Why can a salamander rebuild a lost limb, while mammals usually seal their wounds with scar tissue?

In mice, scientists have now nudged that same emergency repair program onto a different path. By applying two growth signals in sequence, researchers at Texas A&M University prompted amputated neonatal mouse digits to form new bone, joint-like structures, tendon and ligament tissue. The rebuild is imperfect, but at least it challenges the old idea that mammals simply cannot regenerate lost parts.

The Blastema

When a mammal’s tissue is cut or crushed, the body summons fibroblasts, cells that help close the wound and lay down scar tissue. That response can save an animal from infection. It also blocks the more ambitious process seen in salamanders, which build a mound of repair cells called a blastema.

“Why some animals can regenerate and others, particularly humans, can’t is a big question that has been asked since Aristotle,” Dr. Ken Muneoka of Texas A&M, said in a statement. “I’ve spent my career trying to understand that.”

His team amputated mouse digits at a level that normally heals by scarring. After the wound closed, the researchers applied fibroblast growth factor 2, or FGF2. The signal did not grow a toe by itself. But it pushed wound cells to gather into a blastema-like structure and switch on genes associated with regeneration.

“It’s as if these cells can move in two different directions,” Muneoka added. “They could either make a scar or make a blastema. Our research focused on redirecting the behavior of fibroblasts already present at the injury site.”

Four days later, the team added bone morphogenetic protein 2, or BMP2. That second signal told the cells to begin building.

An Imperfect Digit

The result was not a perfect replacement toe. The new structures varied in shape and size, and they did not restore a fully normal digit.

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Still, at the end of the day, it is a regrown digit. The treated digits formed new skeletal elements resembling the lost distal phalanx and sesamoid bone, along with a synovial joint complex, tendon, and ligament tissue. The study reports that the treatment regenerated “all skeletal structures removed by amputation,” though imperfectly.

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The researchers also found signs that the process used similar mechanisms seen in early development. A growth plate formed in the regenerated phalanx-like bone, suggesting the wound cells had been pushed into a more developmental state rather than simply patched over.

This all cuts back on a major assumption in regenerative medicine. Many efforts try to add stem cells from outside the body. But Muneoka and colleagues say the wound may already contain cells capable of rebuilding tissue—if researchers can steer them away from making scar tissue and toward regeneration.

“You don’t have to actually get stem cells and put them back in,” Muneoka explained. “They’re already there—you just need to learn how to get them to behave the way you want.”

A Longer Road to Humans

No one should expect people to regrow fingers from this work anytime soon. A mouse digit is far simpler than a human finger. A functional finger would need nerves, blood vessels, skin, bone, nail, tendon, and joint tissues to grow in the right order and shape.

But the findings have a more immediate implication: better healing after trauma.

“People should start thinking about using these signals during the healing process,” Muneoka said. “Even shifting the response slightly away from scarring could have real benefits.”

That possibility may draw attention because BMP2 already has some approved medical uses, and FGF2 has been tested in clinical settings. The leap from mouse toes to human amputations remains large, but the ingredients are not obscure.

Dr. Larry Suva, a Texas A&M professor and study co-author, framed the work as a change in how scientists view mammalian limits. “The cells that we thought to be unprogrammable, in fact are,” he said. “The capacity is not absent—it’s just obscured.”

The study was published in the journal Nature Communications.