Why amphibians regenerate limbs but mammals cannot

Some animals can regrow lost body parts. Salamanders and frog tadpoles can rebuild entire limbs after amputation. Mammals cannot. For decades, biologists have tried to understand why. Now a research  team has discovered that oxygen plays a crucial role in limb regeneration. By comparing amputated limbs from frog tadpoles and embryonic mice, the researchers found that the way cells sense oxygen determines whether regeneration can even begin. The study is published in Science.

Limb regeneration begins with wound healing. After amputation, cells at the injury site must rapidly seal the wound and switch into regenerative cell types. In amphibians, this process runs smoothly. In mammals, it stalls early. Wound closure is slow and scar formation takes over, blocking regeneration.

One key difference lies in the environment. Amphibian larvae develop in water, where oxygen levels are lower than in the air. Moreover, many regeneration-competent species live in aquatic environments. Meanwhile, mammalian tissues are typically exposed to higher oxygen levels after injury.

What is unclear is whether this difference has played a direct role in regeneration or is merely a consequence of lifestyle.

The researchers amputated developing limbs from frog tadpoles and mouse embryos and cultured them outside the body under controlled oxygen conditions. Oxygen levels were lowered to match aquatic environments or raised to levels close to air.

They tracked how cells responded by measuring wound closure, cell movement, gene activity, metabolism, and epigenetic states, including changes to DNA packaging. The work focused on HIF1A, a protein that acts as a cellular oxygen sensor. When oxygen is low, HIF1A becomes stable and activates programs that set the stage for wound healing and regeneration.

Lowering oxygen levels had a clear effect on the limbs of mouse embryos. Under reduced oxygen, mouse cells closed wounds faster and showed signs of entering a regenerative program. Stabilizing HIF1A produced similar effects, even when oxygen levels remained high.

Low oxygen also changed cell behavior, with skin cells becoming more mobile and altering their mechanical properties. Metabolism shifted toward glycolysis, a process that takes place in low-oxygen states. At the same time, chemical marks on DNA-associated proteins shifted to favor the activation of regeneration-related genes.

Frog tadpoles behaved differently. Their limbs regenerated efficiently across a wide range of oxygen levels, including levels well above those normally found in air. Molecular analysis showed that their cells maintain stable HIF1A activity even when oxygen increases, due to low expression of genes that normally shut this pathway down.

By comparing frogs, axolotls, mice, and human datasets, the team found a consistent pattern. Regeneration-competent amphibians show reduced oxygen-sensing capacity, allowing regenerative programs to be initiated and sustained. Mammals show the opposite pattern. Their cells respond strongly to oxygen and switch regenerative programs off soon after injury.
The results suggest that mammalian limbs retain latent regenerative potential at early stages, depending on how cells respond to environmental signals such as oxygen. This means that adjusting oxygen-sensing pathways might one day improve wound healing or regenerative responses in humans.

Species-specific oxygen sensing governs the initiation of vertebrate limb regeneration, Science (2026). DOI: 10.1126/science.adw8526

Part 2

CAR-T therapy drives remission in patient with three autoimmune diseases

For the first time, scientists have used a modern cell therapy called CAR-T to treat a patient with three different life-threatening autoimmune diseases that had resisted years of treatment. The patient, who once required daily blood infusions, has been in remission without needing additional treatment for a year since the CAR-T therapy. The case report, published in Med, suggests that CAR-T therapies can help treat complex and severe autoimmune diseases.
After being sick for more than a decade, the patient is now in treatment-free remission and able to return to an almost normal life. This therapy significantly improved her quality of life.

CD19 CAR-T therapy induces remission in refractory autoimmune hemolytic anemia with ITP and antiphospholipid syndrome, Med (2026). DOI: 10.1016/j.medj.2026.101075