Mechanisms and translational applications of regeneration in limbs: From renewable animals to humans

Abstract

Background: The regenerative capacity of organisms declines throughout evolution, and mammals lack the ability to regenerate limbs after injury. Past approaches to achieving successful restoration through pharmacological intervention, tissue engineering, and cell therapies have faced significant challenges.

Objectives: This review aims to provide an overview of the current understanding of the mechanisms behind animal limb regeneration and the successful translation of these mechanisms for human tissue regeneration.

Results: Particular attention was paid to the Mexican axolotl (Ambystoma mexicanum), the only adult tetrapod capable of limb regeneration. We will explore fundamental questions surrounding limb regeneration, such as how amputation initiates regeneration, how the limb knows when to stop and which parts to regenerate, and how these findings can apply to mammalian systems.

Conclusions: Given the urgent need for regenerative therapies to treat conditions like diabetic foot ulcers and trauma survivors, this review provides valuable insights and ideas for researchers, clinicians, and biomedical engineers seeking to facilitate the regeneration process or elicit full regeneration from partial regeneration events.

Keywords: Autonomous regeneration; Blastema; Organ regeneration; Salamander.