A new study published in Nature Communications has found evidence that limb regenerative abilities may not be absent in mammals, but instead lie dormant.
In experiments involving mice, researchers from Texas A&M University successfully triggered the regrowth of complex tissues after amputation, including bone, tendons, ligaments and joint structures, by unlocking the dormant regenerative abilities in mammals.
While salamanders can regenerate lost limbs and starfish can regrow entire arms, humans typically heal injuries through scarring rather than replacement. In the study, the researchers found that the regenerative abilities of mammals could be switched off, waiting for the right signals to be reactivated.
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"Why some animals can regenerate and others, particularly humans, can't is a big question that has been asked since Aristotle," said Professor Ken Muneoka, who led the study.
According to scientists, the answer may lie in how the body responds to injury – when mammals are wounded, specialised cells called fibroblasts rush to the site and begin repairing damage. Their usual response is to form scar tissue, a process known as fibrosis. While scarring helps close wounds quickly and prevents infection, it also prevents the regeneration of complex structures.
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In animals such as salamanders, the researchers found that the cells act differently, taking a different path – rather than forming scars, they create a mass of regenerative cells known as a blastema, which acts as a foundation for rebuilding missing tissues.
To determine whether mammalian cells could be redirected down a similar path, the researchers developed a two-stage treatment involving naturally occurring growth factors. The first stage used fibroblast growth factor 2 (FGF2), applied after the wound had healed. This encouraged cells at the injury site to form a blastema-like structure rather than continuing down the scarring pathway.
Researchers then applied a second signal, bone morphogenetic protein 2 (BMP2), which instructed those cells to begin constructing new tissues, with the treated mice successfully regrowing multiple structures normally lost following amputation.
Although the regenerated anatomy was not an exact replica of the original, researchers say the achievement demonstrates that limb regeneration in mammals is possible.
"We regenerated what you would expect to see at that level of injury," said Muneoka. "The structures are there – just not in a perfect form."
The findings also challenge one of the central assumptions of regenerative medicine: that stem cells must be introduced from outside the body to stimulate repair. Instead, the study suggests the cells required for regeneration are already present.
"You don't have to actually get stem cells and put them back in," said Muneoka. "They're already there – you just need to learn how to get them to behave the way you want."
The team also discovered evidence that cells can be reprogrammed to build structures outside their usual developmental role. This process, known as positional re-specification, is a key feature of regeneration in animals capable of regrowing limbs.
While the work remains at an early stage and has only been demonstrated in mice, scientists believe it could eventually lead to new treatments for injuries that currently result in permanent scarring or loss of function. Rather than focusing solely on regrowing missing body parts, future therapies could help wounds heal more effectively, improving tissue repair and reducing fibrosis.
"This changes the way we think about what's possible," said co-author Larry Suva. "Once you show that regeneration can be activated, it opens the door to asking entirely new questions."
