During limb regeneration adult tissue is converted into a zone of undifferentiated progenitors called the blastema that reforms the diverse tissues of the limb. Previous experiments have led to wide acceptance that limb tissues dedifferentiate to form pluripotent cells. Here we have reexamined this question using an integrated GFP transgene to track the major limb tissues during limb regeneration in the salamanderAmbystoma mexicanum (the axolotl). Surprisingly, we find that each tissue produces progenitor cells with restricted potential. Therefore, the blastema is a heterogeneous collection of restricted progenitor cells. On the basis of these findings, we further demonstrate that positional identity is a cell-type-specific property of blastema cells, in which cartilage-derived blastema cells harbour positional identity but Schwann-derived cells do not. Our results show that the complex phenomenon of limb regeneration can be achieved without complete dedifferentiation to a pluripotent state, a conclusion with important implications for regenerative medicine.
Main Author: Malcolm Maden, University of Florida
| Scientists Seek To Mimic Healing Powers Of Salamanders In Humans | 18 Views |
| posted on Friday, July 03, 2009 |  |
| SALAMANDERS, REGENERATIVE WONDERS, HEAL LIKE MAMMALS, PEOPLE physorg.com July 1st, 2009 Original Link 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 embryonic stem cells, 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 scars 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 regeneration 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. |
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