The axolotl’s ability to regrow limbs make it widely studied by scientists hoping to understand regeneration and perhaps mimic the process for healing injuries in people. (Photo: wikimedia commons)

Yes, it’s true; the axolotl is an oddly adorable salamander but it is its ability to regrow complex structures like the legs, tail, retina and spinal cord after injury that fascinate researchers.

Limb regeneration

Unlocking the axolotl’s ability to regenerate tissue may one day guide new therapies for human regeneration. In the May 20 issue of the Proceedings of the National Academy of Science, a team from the Australian Regenerative Medicine Institute reports progress toward that goal. They show that a specific white blood cell—the macrophage—is essential for the axolotl to regrow limbs.

Wound healing

When you hear “white blood cells,” you probably think about fighting off a cold, not regrowing limbs. Macrophages, whose name means “big eater,” do act as a first defense against infection. They travel through the body, devour viruses and bacteria, and release signals that alert other immune cells. But they also play a major role in wound healing by clearing dead cells and supporting new growth.

Wound healing and tissue regeneration may use similar mechanisms. In this study, the researchers removed macrophages from axolotls and then amputated a limb. The result was clear: none of the animals regrew their limbs. When the team added macrophages back and amputated more of the limb, regeneration proceeded normally. This confirmed that macrophages are required for this remarkable ability.

So what difference in macrophage function separates mammalian wound healing from amphibian limb regeneration—and how does that difference give the axolotl its superior talent?

Macrophages

The researchers found that in the first 24 hours after amputation, macrophages secrete proteins that both activate and inhibit the immune system. In wound healing, on the other hand, macrophages are known to secrete activator proteins for several days and then later they release proteins that help slow down the immune response. The authors speculate that stepping on both the accelerator and the brake of the immune system creates the right cellular conditions to kick-start the regeneration process.

Despite these intriguing results, re-growing a severed human foot is a long ways off. Still, as James Godwin, the paper’s first author, said in an interview with The Scientist:

This really gives us somewhere to look for what might be secreted into the wound environment that allows for regeneration.

At CIRM, we’re big fans of this type of fundamental developmental biology research. CIRM grantees like Gage Crump of USC, who has a New Faculty award to study regeneration of facial bones in the zebrafish, are deconstructing how nature builds tissues to help inform the development of stem cell-based therapies that will repair our bodies after injury or illness.

Here’s a 30 second video of Dr. Crump explaining his regeneration research:

T.D.