Regenerate as an axolotl
Recipe in macrophage signaling pathways
Sergey Syrov, XX2 century
Axolotl is a neotenic larva of some species of ambystomes, amphibians from the family Ambystomidae (Ambystomidae).
A group of scientists led by James Godwin from the Mount Desert Biological Laboratory (MDI Biological Laboratory in Bar Harbor, Maine) has brought the mystery of regeneration closer by revealing differences in molecular signals that trigger the mechanism of restoring lost organs in an axolotl and blocking it in an adult mouse.
"Since its foundation in 1898, the staff of the Mount Desert Biological Laboratory has relied on the methods of comparative biology to better understand how to take care of human health," says the president of the scientific institution, Professor Hermann Haller. "The discoveries made by James Godwin in the course of comparative studies of the axolotl and the mouse prove that the idea of learning from nature is as relevant today as it was a hundred and twenty years ago."
Instead of regrowing lost or damaged body parts, mammals usually form a scar at the site of injury. It is important to understand why the axolotl does not form a scar that prevents regeneration in response to injury.
"Our research shows that humans have untapped potential for regeneration,– says Godwin. – If we can solve the problem of scar formation, we will be able to unlock the regenerative potential. Axolotls do not have scars, regeneration takes place. But as soon as a scar is formed, the game ends for regeneration. If we could prevent the formation of scars, we could improve the quality of life of many people."
Axolotl as a model
The Axolotl, a Mexican salamander that is almost extinct in the wild, is an ideal model for research in the field of regenerative medicine. This is the regeneration champion. Most salamanders have some regenerative abilities, but the axolotl can regenerate almost any part of the body, including the brain, heart, jaws, limbs, lungs, ovaries, spinal cord, skin, tail, and so on.
In mammals, embryos and very young individuals have the ability to regenerate, for example, heart tissue can be restored in infants, and children can grow a fingertip. It is likely that adult mammals also retain the genetic code of regeneration. In this case, a therapy can be developed that starts the process of restoring tissues and organs lost as a result of illness or injury, as an alternative to scar formation.
In a previous study, Godwin compared axolotl immune cells, macrophages, with similar mouse cells to determine the quality of axolotl macrophages that promote regeneration. And earlier, Godwin also discovered that it is macrophages that are crucial for regeneration: when they are depleted, the axolotl has a scar, the restoration of the lost fragment of the body does not occur.
Although the signaling of macrophages in axolotl and mouse are similar when these such different organisms encounter pathogens – bacteria, fungi and viruses; but everything changes when an injury occurs: the signaling of axolotl macrophages promoted the growth of new tissue, in the mouse – the formation of scars.
It turned out that the signaling response of a class of proteins known as Toll-like receptors (TLR), which allow macrophages to recognize the threat of infection or tissue damage and induce a pro-inflammatory reaction, was "unexpectedly divergent" in response to damage to axolotl and mouse organisms. This discovery can help scientists understand the mechanisms that control regeneration and learn how to start them.
Take up the "levers of regeneration"
The discovery of an alternative signaling pathway associated with regeneration may eventually lead to the development of regenerative therapies. Although the restoration of a human limb is unlikely in the near future, there may be opportunities to improve the clinical outcomes of diseases in which scars play an important role – and these are very common diseases of the heart, kidneys, liver and lungs.
"We are getting closer to understanding how axolotl macrophages are initiated for regeneration, which, in turn, brings us closer to the moment when the levers of regeneration in humans will become available to us," Godwin notes. –For example, I assume that one day we will be able to use a hydrogel applied to wounds that changes the behavior of human macrophages so that they look more like axolotl macrophages."
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