Macrophages Essential to Limb Regeneration in the Axolotl Emerge from the Liver
Regeneration from injury is an intricate dance between stem cells, somatic cells, senescent cells, and immune cells. In particular, research into the biochemistry of species such the axolotl that can regenerate limbs and organs has identified the innate immune cells known as macrophages as essential to the process. Specific differences in macrophage behavior between more regenerative species such as the axolotl and less regenerative species such as our own are still under exploration. Here, researchers uncover a greater level of complexity in axolotl regeneration, in that only some macrophages are important to scar-free regeneration, and these cells originate in the liver rather than the bone marrow.
In 2013 it was discovered that a type of white blood cell called a macrophage is essential to limb regeneration in the axolotl. Without macrophages, which are part of the immune system, regeneration did not take place. Instead of regenerating a limb, the axolotl formed a scar at the site of the injury, which acted as a barrier to regeneration, just as it would in a mammal such as a mouse or human. Now, in a new study, researchers have identified the origin of pro-regenerative macrophages in the axolotl as the liver. By providing science with a place to look for pro-regenerative macrophages in humans - the liver, rather than the bone marrow, which is the source of most human macrophages - the finding paves the way for regenerative medicine therapies in humans.
Although the prospect of regrowing a human limb may be unrealistic in the short term due to its complexity, regenerative medicine therapies could potentially be employed in the shorter term in the treatment of the many diseases in which scarring plays a pathological role, including heart, lung and kidney disease. "If axolotls can regenerate by having a single cell type as their guardian, then maybe we can achieve scar-free healing in humans by populating our bodies with an equivalent guardian cell type, which would open up the opportunity for regeneration."
Although it remains to be seen if achieving scar-free healing in mammals will allow regeneration to proceed, researchers believe that may be the case. Because mammals already possess the machinery for regeneration - young mice can regenerate, as can human newborns - mammalian regeneration may simply be a matter of removing the barrier posed by scarring. "In axolotls, macrophages act as a brake on fibrosis, or scarring. Humans may possess macrophages that are doing their hardest to repair the damage, but are being held back. If we can engineer human macrophages to promote scar-free healing, we might be able to achieve a huge improvement in repair with just a little tweak. We have the luxury in the salamander of being able to work out which macrophage functions are essential to scar suppression and regeneration, gene by gene if we have to. If we can find out what that is, then maybe we can get that interaction happening in mammals."