Could Humans Regrow Limbs? New Study Reveals Promising Genetic Pathway

A cross-species study has identified key genes that govern regeneration, revealing a potential path toward inducing limb regrowth in humans.

Scientists studying a shared gene in three very different animals, axolotls, mice, and zebrafish, have uncovered a possible path toward a future gene therapy that could help humans regrow lost limbs. The findings were published this week.

“This significant research brought together three labs, working across three organisms to compare regeneration,” said Wake Forest Assistant Professor of Biology Josh Currie, whose lab focuses on the Mexican axolotl salamander. “It showed us that there are universal, unifying genetic programs that are driving regeneration in very different types of organisms, salamanders, zebrafish, and mice.”

The study, published in the Proceedings of the National Academy of Sciences, also involved David A. Brown, a Duke University plastic surgeon who studies digit regrowth in mice, and Kenneth D. Poss of the University of Wisconsin-Madison, who researches fin regeneration in zebrafish.

Globally, more than 1 million amputations occur each year due to conditions such as diabetes, traumatic injuries, cancer, and infections, according to Global Burden of Disease data. This number is expected to increase as the population ages and diabetes becomes more common.

In response, the researchers are exploring options that go beyond prosthetics, aiming to restore the sensory and motor functions of natural limbs.

Their work points to a group of genes known as SP genes, which appear to play a central role in regeneration and are shared across mice, zebrafish, and axolotls.

Therapy makes up for missing gene

Each of the three animals was selected for its unique regenerative abilities.

1. Axolotls can regrow entire limbs, as well as tails that include the spinal cord, and parts of organs such as the heart, brain, liver, lungs, and jaw.
2. Zebrafish are another powerful model. Their tail fins regrow quickly and can do so repeatedly without losing this ability. They can also regenerate the heart, spinal cord, brain, retinas, kidneys, and pancreas.
3. Mice, which are more closely related to humans, can regenerate the tips of their digits. Humans share a similar ability, as fingertips can regrow if the nailbed remains intact, allowing skin, bone, and soft tissue to return.

Currie explained that researchers found the regenerating epidermis, or skin, in all three species produces two key genes, SP6 and SP8. They then investigated how these genes function.

Biology Ph.D. student Tim Curtis Jr. contributed to the work in Currie’s lab, along with undergraduate Elena Singer-Freeman, a Goldwater Scholar and 2025 Wake Forest biochemistry and molecular biology graduate.

Emulating the abilities of salamander genes

In salamanders, SP8 is essential for limb regrowth. Using CRISPR gene editing, Currie’s team removed SP8 from the axolotl genome. Without it, the animals failed to properly regenerate limb bones. Mice missing both SP6 and SP8 showed similar defects in digit regrowth.

Building on these results, Brown’s lab used a regeneration-related enhancer identified in zebrafish to create a viral gene therapy.

The treatment delivers FGF8, a molecule normally activated by SP8, to promote bone regrowth in mouse digits. This approach partially restored regenerative ability even when the original SP genes were absent.

While humans do not naturally have this level of regenerative capacity, the findings suggest that it may one day be possible to mimic these genetic pathways.

“We can use this as a kind of proof of principle that we might be able to deliver therapies to substitute for this regenerative style of epidermis in regrowing tissue in humans,” Currie explained.

Building the foundation for human therapies

Much more research is needed before such techniques could be applied to human limbs. Still, Currie described the study as an important step toward therapies that could restore limbs lost to injury or disease.

“Scientists are pursuing many solutions for replacing limbs, including bioengineered scaffolds and stem cell therapies,” Currie explained. “The gene-therapy approach in this study is a new avenue that can complement and potentially augment what will surely be a multi-disciplinary solution to one day regenerate human limbs.”

He added that collaboration across different research fields played a key role in the project’s success.

“Many times, scientists work in their silos: we’re just working in axolotl, or we’re just working in mouse, or just working in fish,” Currie said. “A real standout feature of this research is that we work across all these different organisms. That is really powerful, and it’s something that I hope we’ll see more of in the field.”

Reference: “Enhancer-directed gene delivery for digit regeneration based on conserved epidermal factors” by David A. Brown, Katja K. Koll, Erin Brush, Grant Darner, Timothy Curtis, Thomas Dvergsten, Melissa Tran, Colleen Milligan, David W. Wolfson, Trevor J. Gonzalez, Sydney Jeffs, Alyssa Ehrhardt, Rochelle Bitolas, Madeleine Landau, Kendall Reitz, David S. Salven, Leslie A. Slota-Burtt, Isabel Snee, Elena Singer-Freeman, Sayuri Bhatia, Jianhong Ou, Aravind Asokan, Joshua D. Currie and Kenneth D. Poss, 14 April 2026, Proceedings of the National Academy of Sciences.
DOI: 10.1073/pnas.2532804123

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