Progress in Understanding Regeneration in Salamanders

Shwann cells are shown here in a salamander limb. When the limb regrew after being amputated, only these cells wrapped around nerve fibers; other cell types did not turn into Shwann cells. Credit: D. Knapp/E. Tanaka

The salamander is a superhero of regeneration, able to replace lost limbs, damaged lungs, sliced spinal cord — even bits of lopped-off brain. In a paper set to appear Thursday in the journal Nature, a team of seven researchers, including a University of Florida zoologist debunk the source of the salamander regeneration as “pluripotent” cells.

The researchers show that cells from the salamander’s different tissues retain the “memory” of those tissues when they regenerate, contributing with few exceptions only to the same type of tissue from whence they came. The new findings suggest that harnessing the salamander’s regenerative wonders is at least within the realm of possibility for human medical science.

The researchers’ main conclusion: Only ‘old’ muscle cells make ‘new’ muscle cells, only old skin cells make new skin cells, only old nerve cells make new nerve cells, and so on. The only hint that the axolotl cells could revamp their function came with skin and cartilage cells, which in some circumstances seemed to swap roles, Maden said.

MIT Technology review has coverage.

Tanaka’s team employed a novel method for tracking the fate of cells from different tissues in a type of salamander called the axolotl. The researchers first created transgenic axolotls that carried green fluorescent protein (GFP) in their entire bodies. When the animals were still embryos, the researchers removed a piece of tissue from the limb region of the transgenic animals and transplanted the tissue into the same location in nontransgenic axolotls. The transplants were incorporated into the growing body as normal cells, and when the limb of the transplant recipients were then severed, the researchers could track the fate of the fluorescent cells as the limb regrew.

Sánchezalso says that the idea that blastemas held several different cell types was a “minority hypothesis” and that this study “shows that this hypothesis turns out to be correct.” He cautions that scientists now need to determine whether this phenomenon is the same in adult axolotls and in newts, which are a primary model organism for regeneration studies. But if the same mechanism turns out to underlie other cases of regeneration, it would change what scientists believe is required to regrow body parts, Sánchezsays. But it leaves a major question unanswered: if humans already have tissue-specific stem cells, what exactly is the difference between our cells and those of salamanders?

Maden said the findings will help researchers zero in on why salamander cells are capable of such remarkable regeneration. “If you can understand how they regenerate, then you ought to be able to understand why mammals don’t regenerate,” he said.

Maden said UF researchers will soon begin raising and experimenting on transgenic axolotls at UF as part of the The Regeneration Project, an effort to treat human brain and other diseases by examining regeneration in salamanders, newts, starfish and flatworms.