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PLoS One 2012 Jan 01;74:e32875. doi: 10.1371/journal.pone.0032875.
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Skin regeneration in adult axolotls: a blueprint for scar-free healing in vertebrates.

Seifert AW , Monaghan JR , Voss SR , Maden M .

While considerable progress has been made towards understanding the complex processes and pathways that regulate human wound healing, regenerative medicine has been unable to develop therapies that coax the natural wound environment to heal scar-free. The inability to induce perfect skin regeneration stems partly from our limited understanding of how scar-free healing occurs in a natural setting. Here we have investigated the wound repair process in adult axolotls and demonstrate that they are capable of perfectly repairing full thickness excisional wounds made on the flank. In the context of mammalian wound repair, our findings reveal a substantial reduction in hemostasis, reduced neutrophil infiltration and a relatively long delay in production of new extracellular matrix (ECM) during scar-free healing. Additionally, we test the hypothesis that metamorphosis leads to scarring and instead show that terrestrial axolotls also heal scar-free, albeit at a slower rate. Analysis of newly forming dermal ECM suggests that low levels of fibronectin and high levels of tenascin-C promote regeneration in lieu of scarring. Lastly, a genetic analysis during wound healing comparing epidermis between aquatic and terrestrial axolotls suggests that matrix metalloproteinases may regulate the fibrotic response. Our findings outline a blueprint to understand the cellular and molecular mechanisms coordinating scar-free healing that will be useful towards elucidating new regenerative therapies targeting fibrosis and wound repair.

PubMed ID: 22485136
PMC ID: PMC3317654
Article link: PLoS One
Grant support: [+]

Species referenced: Xenopus
Genes referenced: acta2 acta4 actc1 actl6a dio3 fn1 gtsf2 krt12.4 lcp1 mmp2 mmp28 pnma2 tnc

Article Images: [+] show captions
References [+] :
Aarabi, Hypertrophic scar formation following burns and trauma: new approaches to treatment. 2007, Pubmed