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Vertebrate tissue repair and regeneration - Previous and Current Research

Fig. Axolotl limb with muscle fibres labeled with GFP via embryonic transplantation. Insert: Graphical abstract depicting the diversity of cellular mechanisms among salamanders to successfully regenerate muscle.

Figuring out how to unlock the inherent regeneration potential in mammals and specifically in humans requires a practical model of regeneration. Axolotl is a powerful model where transgenesis has proven useful for studying molecular and cellular mechanisms of regeneration. Another advantage of this animal model is its semitransparent body, allowing intra-vital imaging of the limb. Axolotl represents a simplified organism in comparison with mammals, yet more complex than other animal models, that is uniquely suited to study bone formation, and appendage phenotypes.

One relevant feature unveiled by studying axolotl limb regeneration is that some mature cells can de-differentiate, a process by which and adult cell acquires a progenitor state. Another mechanism by which a tissue can regenerate is by activating resident stem cells. Recently, we found that muscle fibers do not contribute to new muscle regeneration but rather muscle-specific stem cells differentiate to form new fibers. Although mammalian limb regeneration is far from becoming a reality, with this study we found that axolotls and mammals share a common underlying mechanism for muscle regeneration. In other tissue types, it is unclear the presence of resident stem cells or the multipotency of its progenitors. Such an example is the connective tissue, which plays a critical role in the formation of the regenerating structure called the blastema.

Currently, we are using the cre/loxP system to lineage trace connective tissue populations and their descendants during regeneration and wound healing. Rodents and humans can regenerate a digit tip when amputated at the distal end of the third phalanx (P3). In both, mouse and human, the digit fails to regenerate when amputation occurs more proximal or through the second phalanx (P2), resolving by wound healing. Thus, the digit tip provides a common ground for cross-species studies in regenerative medicine. 

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