Scar-free wound healing and regeneration in amphibians: Immunological influences on regenerative success

• Published in: Differentiation (London) 2014-01, Vol.87 (1-2), p.66-75
• Main Authors: Godwin, James W., Rosenthal, Nadia
• Format: Article
• Language: English
• Subjects: Amphibian; Animals; Anura - growth & development; Anura - immunology; Cicatrix - immunology; Cicatrix - pathology; Extracellular Matrix - immunology; Humans; Immune system; Regeneration; Regeneration - immunology; Scarring; Skin - immunology; Stem-cells; Urodela - growth & development; Urodela - immunology; Wound healing; Wound Healing - immunology
• ISSN: 0301-4681; 1432-0436
• DOI: 10.1016/j.diff.2014.02.002

Salamanders and frogs are distinct orders of Amphibians with very different immune systems during adult life, exhibiting varying potential for scar free repair and regeneration. While salamanders can regenerate a range of body parts throughout all stages of life, regeneration is restricted to early stages of frog development. Comparison of these two closely related amphibian orders provides insights into the immunological influences on wound repair, and the different strategies that have evolved either to limit infection or to facilitate efficient regeneration. After injury, cells of the immune system are responsible for the removal of damaged cells and providing a cohort of important growth factors and signaling molecules. Immune cells not only regulate new vessel growth important for supplying essential nutrients to damaged tissue but, modulate the extracellular matrix environment by regulating fibroblasts and the scarring response. The profile of immune cell infiltration and their interaction with local tissue immune cells directly influences many aspects of the wound healing outcomes and can facilitate or prevent regeneration. Evidence is emerging that the transition from wound healing to regeneration is reliant on immune cell engagement and that the success of regeneration in amphibians may depend on complex interactions between stem cell progenitors and immune cell subsets. The potential immunological barriers to mammalian regeneration are discussed with implications for the successful delivery of stem cell therapeutic strategies in patients. •Frogs and salamanders have different adult immune systems.•Both amphibian orders exhibit different potential for scar-free repair and regeneration.•Strong adaptive immune systems are correlated with a restriction in regenerative potential.•The immunological influences on scar-free repair and regeneration are discussed.