CRISPR stem cell therapy grants lizards new regeneration powers
Lizards are famous for their regeneration, able to regrow their tails on demand, but the new tail is not quite perfect. Now, researchers at the University of Southern California (USC) have used stem cell therapy to let lizards grow better tails – bones, nerves and all – in an advance that could have implications for better wound healing in humans.
When certain species of lizard are threatened, they can drop their tails to evade predators, then grow a new one over a few weeks or months. However, the replacement tail is far from a perfect replica – it’s supported by a solid tube of cartilage, instead of a spinal column containing bones and nerves.
But for the new study, the USC researchers found a way to get lizards to regenerate tails much closer to their originals. The technical term is “dorsoventral patterning,” where the dorsal or upper side is made up of skeletal and nerve tissue, while the lower or ventral side is all cartilage. For some reason, regrown tails are completely “ventralized” to grow cartilage.
To figure out what’s happening, the team analyzed and compared how lizard tails form during embryonic development and during regeneration as adults. In both cases, the building work is done by neural stem cells (NSCs), and the team identified a molecular signal they produce that ventralizes tissue, growing cartilage. Embryonic NSCs only produce this signal on the underside of the tail, while adult NSCs do so top and bottom, creating the cartilage tube.
The team tried a few things to stop this ventralization process in regenerated tails. They tried blocking the signal in adult NSCs, but new nerve tissue still didn’t regrow in the upper tail section. They tried implanting embryonic NSCs into the tail stumps of adults, but they still responded to the ventralizing signal.
So the researchers used CRISPR to edit embryonic NSCs so that they wouldn’t respond to this signal. Then, these were implanted into adult lizards’ tail stumps – and sure enough, “perfect” tails were regenerated, with bones and nerves on the top side.
For now, the results are only directly good news for lizards, but the find could eventually inform studies that might lead to advances in human regenerative medicine.
“This study has provided us with essential practice on how to improve an organism’s regenerative potential,” says Thomas Lozito, corresponding author of the study. “Perfecting the imperfect regenerated lizard tail provides us with a blueprint for improving healing in wounds that don’t naturally regenerate, such as severed human limbs and spinal cords. In this way, we hope our lizard research will lead to medical breakthroughs for treating hard-to-heal injuries.”
The research was published in the journal Nature Communications.