Macrophages Key In Salamander Regeneration
May 21, 2013

Macrophages Play Critical Role In Salamander Limb Regeneration

Brett Smith for - Your Universe Online

For years, scientists have considered salamanders the ℠Holy Grail´ of biological regeneration. Now, a new study in the Proceedings of the National Academy of Sciences has revealed an exciting step forward in the quest to adapt this ability for medical use in humans.

Based on experiments with the tiny amphibians, researchers from the Australian Regenerative Medicine Institute at Monash University have found that elements of a salamander´s immune system called macrophages play a key role in enabling the regenerative process.

"Previously, we thought that macrophages were negative for regeneration, and this research shows that that's not the case — if the macrophages are not present in the early phases of healing, regeneration does not occur," said lead author James Godwin, a research fellow at the institute.

The Australian researchers focused their study on the axolotl, an aquatic amphibian also known as the Mexican salamander. They found that removing macrophages from the salamanders eliminated their regenerative abilities, causing tissue scarring.

Macrophages also play a role in the mammalian immune system, engulfing and digesting infection-causing pathogens at the wound site, and generating the inflammatory and anti-inflammatory signals for healing.

In the study, researchers detected signals of“¯inflammation“¯at the salamanders´ wound sites within a day of the amputations. However, anti-inflammatory signals were also present after a single day. In mammals, the anti-inflammatory response occurs much later, typically after two to four days.

The researchers also saw macrophages at the wound, reaching maximum concentration four to six days after the injury. To investigate the role of macrophages in the process, the team injected the amphibians with a chemical substance capable of destroying or depleting these cells.

Salamanders that completely lost their macrophages failed to generate new limbs and formed considerable scar-tissue buildup instead. Salamanders that still had some of their macrophages could still regenerate lost limbs at a slower than normal pace.

Once the salamanders´ macrophage levels returned to normal through natural processes, the researchers re-amputated several limbs, which then fully regenerated at the normal rate. These results indicate the essential role that macrophages play in the wound-healing process.

"Now, we need to find out exactly how these macrophages are contributing to regeneration,” Godwin said. “Down the road, this could lead to therapies that tweak the human immune system down a more regenerative pathway."

Besides the fantastical ability to re-grow arms, legs or even spinal cords, Godwin suggested that learning about the healing abilities of salamanders could show the way to new treatments for other common conditions that are linked to fibrosis or scarring, such as liver disease. The technology could also improve a patient´s recovery following surgery.

“Some of these regenerative pathways may still be open to us. We may be able to turn up the volume on some of these processes," Godwin said. "We need to know exactly what salamanders do and how they do it well, so we can reverse-engineer that into human therapies."

In the meantime, he said, "we can look to salamanders as a template of what perfect regeneration looks like."