Can People Regenerate Body Parts? (I of V)

Scientific American Magazine - By Ken Muneoka, Manjong Han and David M. Gardiner

Progress on the road to regenerating major body parts, salamander-style, could transform the treatment of amputations and major wounds.

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.

Humans have long wondered how the salamander pulls off this feat. How does the regrowing part of the limb “know” how much limb is missing and needs to be replaced? Why doesn’t the skin at the stump form a scar to seal off the wound as it would in humans? How can adult salamander tissue retain the embryonic potential to build an entire limb from scratch multiple times? Biologists are closing in on the answers to those questions. And if we can understand how the regeneration process works in nature, we hope to be able to trigger it in people to regenerate amputated limbs, for example, and transform the healing of other major wounds.

The human body’s initial responses to such a serious injury are not that different from those of a salamander, but soon afterward the human and amphibian wound-healing strategies diverge. Ours results in a scar and amounts to a failed regeneration response, but several signs indicate that humans do have the potential to rebuild complex parts. The key to making that happen will be tapping into our latent abilities so that our own wound healing becomes more salamanderlike. For this reason, our research first focused on the experts to learn how it is done.

When the tiny salamander limb is amputated, blood vessels in the remaining stump contract quickly, so bleeding is limited, and a layer of skin cells rapidly covers the surface of the amputation site. During the first few days after injury, this so-called wound epidermis transforms into a layer of signaling cells called the apical epithelial cap (AEC), which is indispensable for successful regeneration. In the meantime, fibroblasts break free from the connective tissue meshwork and migrate across the amputation surface to meet at the center of the wound. There they proliferate to form a blastema—an aggregation of stemlike cells that will serve as progenitors for the new limb.

Now, as we watch a salamander grow back an arm, we are no longer quite as mystified by how it happens. Soon humans might be able to harness this truly awesome ability ourselves, replacing damaged and diseased body parts at will, perhaps indefinitely.

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