Adult newts are the envy of the animal kingdom when it comes to replacing missing tissue. Amputated legs, arms or tails, there's hardly repair job too big for this animal's remarkable regenerative abilities. For the first time, scientists have pinpointed the mechanism used by the amphibian to regrow missing body parts, a development they say will offer clues to muscle regeneration in mammals.
A team of scientists from the University of Tsukuba, Japan, and the University of Dayton, Ohio, set out to investigate the role of two types of cells believed to play a key role in a newt's muscle regeneration: skeletal muscle fiber cells (SMFCs) and muscle stem/progenitor cells (MPCs). MPCs are dormant cells that live in the muscle fiber and can be recruited to multiply into specialized muscle cells.
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The researchers added a gene to Japanese fire bellied newt embryos that was linked to a red fluorescent protein and known to be active in SMFCs, allowing them to track its activity throughout the muscle regeneration process. MPC activity was assessed through tissue sample collection and cell-specific staining.
The team allowed one group of newts to grow to three months, the swimming larval stage, and another to 16 months, the metamorphosed juvenile stage. Then, with the animals anaesthetized, they starting lopping off the limbs.
What the scientists found was that the younger newts regenerated their tissue primarily through the MPCs, rather than SMFCs. In the adult newts, the researchers found that the SMFCs actually regressed, re-entered the cell cycle and then proliferated to generate more muscle cells.
"Larval newts use stem/progenitor cells for new muscle in a regenerated limb while metamorphosed newts recruit muscle fiber cells in the stump for the same purpose," says Hibiki Tanaka from the University of Tsukuba.
The researchers do note that these regenerative powers are unlikely to be recreated in humans, but by establishing how exactly they work can further our understanding of mammal tissue regeneration and wound healing.
"The newt switches the cellular mechanism for limb regeneration from a stem/progenitor-based mechanism (larval mode) to a dedifferentiation-based one (adult mode) as it transits beyond metamorphosis," says Chikafumi Chiba from the University of Tsukuba. "Delineating the mechanisms of these strategies will undoubtedly provide clues for regeneration in other species including mammals."
The research was published in the journal Nature Communications.