Improved healing factor: Stem cells help lizards regrow better tails

In the realm of animal superpowers, there are few things less mind-boggling than regeneration. Humans with limb loss or spinal injury might look at animals like lizards with more than a little envy. Their ability to regrow their lost tails has inspired at least one comic book character in Dr. Curt Connors, whose desire to regain a lost limb led him to experimenting on himself with lizard DNA. The results were less than ideal.

In the real world, scientists are likewise looking to lizards in hopes of cracking the code of their incredible healing ability. Regeneration in lizards, however, is imperfect. Their regrown tails, while sufficient for their needs, lack some of the basic structures present in their original tails.

“Lizards are amazing, and they’re the closest relatives to humans that are able to regenerate an appendage,” Thomas Lozito, a scientist in the Department of Stem Cell Biology and Regenerative Medicine at the University of Southern California, told SYFY WIRE. Lozito and colleagues are studying the gaps in lizard regeneration with an eye toward improving the process as a roadmap for improved healing in people. “Lizards regenerate tissues like spinal cord and cartilage that humans are really bad at repairing, let alone regenerating. If we can improve the regeneration in the lizard, we can use that perhaps as a blueprint for improving a non-regenerative animal like the human.”

There are, of course, other animals with more impressive regenerative abilities than lizards. Axolotls, for instance, are capable of not only regenerating tails, but limbs as well. The reason lies in a property known as neoteny, which causes axolotls to retain their larval state even in adulthood. Because they never complete metamorphosis, when a body structure is lost, they are capable of restarting the embryonic generative processes which built their bodies in the first place. It’s the ultimate bodybuilding cheat code.

Where lizards are special is that they are amniotes, like humans, who retain at least some ability to regenerate a lost appendage. But because they don’t retain their embryonic processes, their regenerated tails lack some of the sophistication of the original.

Lizards primarily use their tails for fat storage and in some lizards the simplified regenerated tail has shown to be more effective at storing fat. This may be the primary driver behind the simplified tail regeneration. There’s no ecological or evolutionary pressure to build a more complex structure when a simple one will do.

“There are multiple imperfections in the regenerated lizard tail. They lack dorsoventral patterning, they also lack any segmentation along the tail’s length, and they lack bones. We fixed the patterning, the other two are still being studied,” Lozito said.

Photo: Thomas Lozito, University of Southern California

Using embryonic stem cells, Lozito and team were able to jumpstart the patterning process, allowing lizards to recreate more perfect regenerated tails. Getting those stems cells also required a bit of out of the box thinking.

Because lizards exhibit the same sorts of tissue rejection as humans when presented with implanted tissue, the team needed a way to get around those challenges. Using stem cells from genetically different individuals would have required immunosuppressant drugs, which have been shown to have a negative impact on the regenerative process, so that was out as a solution. Instead, they used a colony of genetically identical lizards.

“Our colony at USC began with a single female and now we have over a thousand lizards in our colony all derived from that single female, all genetically identical,” Lozito said. “We can take stem cells from any individual in our colony and place them into anyone else without rejection.”

Building up to a large colony of genetically identical lizards did not require the introduction of any additional scientific meddling, however. They just needed another of nature’s cool tricks. The team used mourning geckos (Lepidodactylus lugubris), a naturally parthenogenic species which is almost entirely female and reproduces asexually. This provides researchers with a steady supply of embryonic stem cells and compatible test subjects.

Utilizing those stem cells solved the patterning problem and appears to provide a potential solution for segmentation as well. There are, likewise, populations of embryonic tissues involved in tail segmentation which are no longer present in adults. The final piece, ossification of cartilage to bone, may be the most difficult of the missing regenerative components, Lozito said.

Because lizards share properties with humans while still being able to regenerate certain tissues, Lozito hopes their research might open up new therapies for treating injury or limb loss.

“Humans are almost completely unable to heal spinal cord injury,” Lozito said. “They form a scar that prevents axon reattachment across the severed gap. Looking at the lizard which at least manages some spinal cord regeneration with the formation of new neurons, perhaps we can use that knowledge to augment human spinal cord injury healing.”

For now, at least, regeneration in lizards seems to be isolated to tail structures. Lozito and team also implanted stem cells onto amputated limbs. They did see some regeneration, but of tail-like structures, not the limb in question. “Wherever on the lizard you implant these neural stem cells, under the right conditions, you can grow tails anywhere on the lizard,” Lozito said.

All of which suggests that Curt Connors’ regained limb should have looked less like an arm and more like a floppy, cartilaginous, unsegmented tail structure, filled with fat. Science can only do so much. What are you going to do?