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Nagoya University clarify mechanism behind rapid tendon regeneration in newts — Comparisons with mice show that simple structure is key

2024.01.11

A research group led by Graduate Student Fumiya Sato (at the time of research), Associate Professor Eijiro Maeda, and Professor Takeo Matsumoto of the Graduate School of Engineering at Nagoya University, in collaboration with Hiroshima University, Hokkaido Chitose College of Rehabilitation, and Rakuno Gakuen University, announced that they have uncovered the mechanism of the complete regeneration of damaged tendons in newts and possible indications for its application in humans. The group used the Iberian newt, which is known for its capability to regenerate its limbs and heart, and demonstrated that they can fully regenerate severed tendons through a straightforward structural and repair procedure. The results are expected to be useful in the regeneration of ligaments with similar structures. The results were published in the November 6 issue of Journal of Orthopaedic Research.

Newts can restore the strength of severed tendons without forming scar tissue in as little as 3 months. However, in mammals (including humans), most tendon injuries are not fully reversible.

The Iberian ribbed newt is the largest newt in the world and is of comparable size to a mouse. The research group directly compared the two animals. The common tendon between them is the flexor tendon, which extends from the middle toe of the hind foot (metatarsal flexor tendon flexes the middle toe of the foot; the tendon connects muscle and bone). At 6 or 12 weeks after complete transection surgery, the regenerated tendon was obtained, and material (tensile) tests and tissue observations were performed.

In newts, severed tendons were joined by new regenerated tendon-like tissue at 6 weeks post operation. The regenerated tissue was as strong as healthy tendons at 12 weeks. In mice, after transection, healing tissue distinct from the tendon formed to encircle the entire severed tendon, and its strength remained significantly lower than that of the healthy tendon at 12 weeks post operation.

A comparison of the structure of healthy tendon and healed regenerated tissue at the nanometer scale revealed that their structures were very different in mice but similar in newts. Comparison of healthy tendons in each animal revealed that newt tendons have a simpler structure than those of mice.

Concentrating on the regeneration of mildly damaged tissue, a process also achievable in humans, the study unveiled distinctions in the healing and regenerative capabilities, as well as the underlying mechanisms, between newts and mammals such as mice and humans.

Maeda stated, "It seems natural that a severed tendon would regenerate completely in newts, which can regenerate its limb and even its heart. However, such 'common sense' in newts is not present in mice. In the future, we will continue to clarify the novel tendon 'manufacturing' mechanism in newts and endeavor to develop a method to replicate it in mice and humans."

Journal Information
Publication: Journal of Orthopaedic Research
Title: Biomechanical analysis of tendon regeneration capacity of Iberian ribbed newts following transection injury: Comparison to a mouse model
DOI: 10.1002/jor.25705

This article has been translated by JST with permission from The Science News Ltd. (https://sci-news.co.jp/). Unauthorized reproduction of the article and photographs is prohibited.

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