Key Concepts

• The gold standard for limb regeneration is the salamander, which can grow perfect replacements for lost body parts throughout its lifetime. Understanding how can provide a road map for human limb regeneration.
• The early responses of tissues at an amputation site are not that different in salamanders and in humans, but eventually human tissues form a scar, whereas the salamander’s reactivate an embryonic development program to build a new limb.
• Learning to control the human wound environment to trigger salamanderlike healing could make it possible to regenerate large body parts.

A salamander’s limbs are smaller and a bit slimier than those of most people, but otherwise they are not that different from their human counterparts. The salamander limb is encased in skin, and inside it is composed of a bony skeleton, muscles, ligaments, tendons, nerves and blood vessels. A loose arrangement of cells called fibroblasts holds all these internal tissues together and gives the limb its shape.

Yet a salamander’s limb is unique in the world of vertebrates in that it can regrow from a stump after an amputation. An adult salamander can regenerate a lost arm or leg this way over and over again, regardless of how many times the part is amputated. Frogs can rebuild a limb during tadpole stages when their limbs are first growing out, but they lose this ability in adulthood. Even mammalian embryos have some ability to replace developing limb buds, but that capacity also disappears well before birth. Indeed, this trend toward declining regenerative capacity over the course of an organism’s development is mirrored in the evolution of higher animal forms, leaving the lowly salamander as the only vertebrate still able to regrow complex body parts throughout its lifetime.

   
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