Author Spotlight: Exploring Regeneration in Axolotls Through Insights in Cellular and Molecular Mechanisms, Bone Healing, and Implications for Human Therapies

We study tetrapod regeneration and use the axolotl as a top-tier regenerative species, comparing it to frogs and mice to discover cellular and molecular mechanisms of regeneration. The development of transgenics in genome editing, assembly of the axolotl genome, and application of RNA-Seq, ATAC-Seq, spatial transcriptomics and proteomics allow us to deeper understand the regeneration microenvironment and compare it to less regenerative species, including humans. We established the cellular contribution to tissues in the regenerating limb and spinal cord, and major regulators of initial cell proliferation and positional identity in the blastema.

In a recent paper, we showed axolotl bone healing going through endochondral ossification, and the cellular level was similar to that of mammals. In contrast to previous techniques, where the axolotl fracture was either unfixed or the neighboring bone served as a support, in the current protocol, the bone is fixated with a plate, thus allowing to create a reproducible and aligned fracture and enabling a sound comparison to the studies in mice. The protocol allows for stable fracture with fixed gap size, broadening the studies on plate fixated fractures to amphibians.

Despite their extreme regeneration abilities and full limb restoration upon amputations, axolotl surprisingly cannot heal large bone fractures with critical size defects. We aim to define the pro-regenerative blastema factors to treat bone non-union in critical size defects.