Salamanders, regenerative wonders, heal like mammals, people

Pacific Giant Salamander (Dicamptodon tenebrosus)
Pacific Giant Salamander (Dicamptodon tenebrosus). Via Wikipedia

The salamander is a superhero of regeneration, able to replace lost limbs, damaged lungs, sliced spinal cord -- even bits of lopped-off brain. But it turns out that remarkable ability isn't so mysterious after all -- suggesting that researchers could learn how to replicate it in people.

Scientists had long credited the diminutive amphibious creature's outsized capabilities to "pluripotent" cells that, like human , have the uncanny ability to morph into whatever appendage, organ or tissue happens to be needed or due for a replacement.

But in a paper set to appear Thursday in the journal Nature, a team of seven researchers, including a University of Florida zoologist, debunks that notion. Based on experiments on genetically modified axolotl salamanders, 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.

Standard mammal stem cells operate the same way, albeit with far less dramatic results -- they can heal wounds or knit bone together, but not regenerate a limb or rebuild a spinal cord. What's exciting about the new findings is they suggest that harnessing the salamander's regenerative wonders is at least within the realm of possibility for human medical science.

"I think it's more mammal-like than was ever expected," said Malcolm Maden, a professor of biology, member of the UF Genetics Institute, and author of the paper. "It gives you more hope for being able to someday regenerate individual tissues in people."

Also, the salamanders heal perfectly, without any whatsoever, another ability people would like to learn how to mimic, Maden said.

Axolotl salamanders, originally native to only one lake in central Mexico, are evolutionary oddities that become sexually reproducing adults while still in their larval stage. They are useful scientific models for studying because, unlike other salamanders, they can be bred in captivity and have large embryos that are easy to work on.

When an axolotl loses, for example, a leg, a small bump forms over the injury called a blastema. It takes only about three weeks for this blastema to transform into a new, fully functioning replacement leg -- not long considering the animals can live 12 or more years.

The cells within the blastema appear embryonic-like and originate from all tissues around the injury, including the cartilage, skin and muscle. As a result, scientists had long believed these cells were pluripotential -- meaning they came from a variety of sites and could make a variety of things once functioning in their regenerative mode.

Maden and his colleagues at two German institutions tested that assumption using a tool from the transgenic kit: the GFP protein. When produced by genetically modified cells, GFP proteins have the useful quality of glowing livid green under ultraviolet light. This allows researchers to follow the origin, movement and destination of the genetically modified cells.

The researchers experimented on both adult and embryonic salamanders.

With the embryos, the scientists grafted transgenic tissue onto sites already known to develop into certain body parts, then observed how and where the cells organized themselves as the embryo developed. This approach allowed them to see, literally, what tissues the transgenic tissue made. In perhaps the most vivid result, the researchers grafted GFP-modified nerve cells onto the part of the embryo known to develop into the nervous system. Once the creatures developed, ultraviolet light exams of the adults revealed the GFP cells stretched only along nerve pathways -- like glowing green strings throughout the body

With the adults, they took tissue from specific parts or organs from transgenic GFP-producing axolotls, grafted it onto normal axolotls, then cut away a chunk of the grafted tissue to allow regeneration. They could then determine the fate of the grafted green cells in the emerging blastema and replacement tissue.

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.

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 , newts, starfish and flatworms.

Source: University of Florida (news : web)

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Jul 01, 2009
I hate this branch of science, in spite of the medical marvels it promises.

This is one of the most dangerous, if not THE most dangerous branches of science in existence.

And of course, even if and when benefits begin to be available to humanity from this research, only the "rich and famous" are going to have access to it.

Jul 01, 2009
Well plus the Salamanders too... oh and i suppose the GEICO gecko will have access to it as well as he is now also rich and famous...

Jul 01, 2009
And of course, even if and when benefits begin to be available to humanity from this research, only the "rich and famous" are going to have access to it.

initial costs are high. that's why only a few (companies, or even states) have R&D. patents last for i think about 10 years (at least in our jurisdiction). then everyone can have access. the government can even buy off that 10 years and make it available instantly. anymore qualms?

Jul 02, 2009
If people who have become partially disabled can be given back a good and productive life by articifially induced regeneration, I find no fault with it.
Besides, the cost of regenerative nmedicine should be weighed against the cost of caring for disabled, who often cannot work because of their injuries.
Now, if ths kind of regenerative medicine can also be applied to the brains of stroke victims, there will be a stampede of institutes and companies willing to spend money on developing the process. The patients will range from young people that have become paraphlegic, to the elderly who need to exercise the mind and body to slow down the process of ageing, but are disabled by strokes and thus tend to age more rapidly.

Jul 02, 2009
The argument against developing any technology - "only the rich and famous are going to have access to it". You know - like computers, cars, antibiotics...

BTW, there is also a strain of lab mice that can regenerate:

Jul 02, 2009

The real argument against developing trans-genic technology is found in plain sight, in science fiction. Though often exaggerated, many things in science fiction are very much real. Reality is sometimes even worse than the horror/thriller science fiction movie.

Invasive species can already devastate environments.

An escaped lab animal (often mice and other rodents, or flies or roaches,) *ahem*, one of these with transgeneic transgenic regeneration could totally wreck the environment, especially if its able to pass the transgenic trait(s) on to offspring, as some of the japanese experiments have already succeeded in doing.

Jul 02, 2009
lookin forward to it :-), human regeneration that is. Though that wired article on the mice stated that they passed it on to their offspring.

Jul 02, 2009
Genetically altered humans with regenerative ability might develop very strange illnesses. How healthy and stable are such genetic mutations? Has Nature missed something the way mammals are?

Jul 02, 2009

And of course, even if and when benefits begin to be available to humanity from this research, only the "rich and famous" are going to have access to it.


If you are worried about affording care only available to the rich and famous, then become rich or famous. I'm neither rich nor famous but I wont complain about people that can afford things that I can't. There is no written right to affordable "limb regeneration" or did I miss that in the new health care legislation that hasn't been totally written, nobody has totally read and the Dems have voted totally yes too. Go figure?

Jul 06, 2009
Hm, perfect regeneration vs. genetically enhanced autoimmune disease (at least in those MRL mice.) I think I'd rather avoid getting injured, than saddle myself with lupus...

I agree with Koen: I'll get a lot more excited about this research when it demonstrates no negative side-effects over life-long trials. And does so on chimps, rather than mice or salamanders... (In other words, not in my lifetime.)

Aug 08, 2009
initial costs are high. that's why only a few (companies, or even states) have R&D. patents last for i think about 10 years (at least in our jurisdiction).

Odd jurisdiction. In most countries its 20 years these days. I think it used to be 18 in the US but was changed to match international standards. In any case the standard is now 20.


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