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Stem Cells Regenerate A Perfect Lizard Tail For The First Time In 250 Million Years

Lizards are able to return to their tails to regenerate them, which makes them the closest relatives to humans capable of regenerating an appendix that has been lost. The replacement structure, which is made up of a cartilage tube and a spinal column, replaces the original tail. A study by USC (University of Southern California) published in Nature Communications reveals how stem cells can be used to help lizards regenerate their tails. This could have implications for human wound treatment.

“This is the first case in which the regeneration process of an appendix in any reptile, bird, or mammal has been significantly improved by stem cell-based therapy. It informs efforts to improve wound healing in humans. He says Dr. Thomas P. Lozito, an assistant professor of orthopedic surgery, stem cell biology, and regenerative medicine at USC’s Keck School.

“Perfecting the imperfectly regenerated tail of lizards provides us with a plan for improving healing in wounds which do not naturally regenerate, such as those that have severed human limbs or spinal cord.”

These improved lizard tails have what is called a “dorsoventral” pattern. This means that they have nerve tissue and skeletal tissue on their dorsal and ventral sides, respectively.

Lozito says that lizards have been around for over 250 million years and no lizard has ever created a dorsoventral tail. My laboratory created the first stamped skeleton-regenerated lizard tails.

The team of scientists at the University of Pittsburgh and the USC medical school compared how lizard tails develop during embryonic development to determine this. Both cases involve neural stem cells, or NSCs, which are the stem cells that make the nervous system.

Adult NSCs create a molecular signal which blocks skeletal or nerve formation and stimulates cartilage development, effectively ventralizing both ends of the tail. The cartilage tube is typical of regenerated tails. Adult NSCs cannot generate nerve tissue on the dorsal side if there is no ventralizing signal.

Gene Editing Tools

Embryonic NSCs, however, produce this “ventralizing” signal only in the area of cartilage that forms the ventral or underside of the tail. In the absence of this signal, however, the dorsal or upper side develops skeletal tissue and nerve tissue. The tail thus acquires the dorsoventral pattern of the embryonic appendages.

However, embryonic NSCs implanted in adult tail stumps will respond to the ventralizing signals and not develop into dorsal structures.

Lozito’s group used gene editing tools in order to make embryonic NSCs nonresponsive to the ventralizing signal. They surgically implanted these cells into the adult tail stumps to create perfect tails.

Lozito concludes, “This study has given us essential practice in how to improve an organism’s regenerative potential.” The imperfectly regenerated lizard tail gives us a blueprint for improving healing of wounds that don’t regenerate naturally like severed human limbs or spinal cords. We hope our research on lizards leads to medical breakthroughs for difficult-to-heal injuries.

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