Scarless wound healing: exploiting the regenerative properties of the spiny mouse

Grantee: Sofia Ferreira Gonzalez, Fellow, University of Edinburgh

Amount: DKK 3,995,846

Grant category: Research Grants in open competition

Year: 2023

Geography: United Kingdom

Sofia Ferreira Gonzalez’s project aims to characterize the regenerative capacity of the spiny mouse – the only mammal known to fully regenerate skin with minimal scarring – to optimize future wound treatment in humans.

Skin fibrosis is often a sequela of suboptimal wound healing following significant epidermal and/or dermal injury (burns, trauma, major surgeries). Fibrotic material replaces native skin with dense, non-functional connective tissue, ultimately leading to loss of function. In its mildest form, fibrosis is a minor aesthetic problem, but in the most severe cases it can lead to debilitating skin pathologies that result in limited movement, high morbidity, and prevention of patient reintegration into society.

Current treatments for fibrosis include physical therapy and surgery, but there are no therapies that directly target the underlying cellular and molecular mechanisms of skin fibrosis.

The spiny mouse (Acomys) is, to date, the only mammal capable of skin autotomy (i.e., self-amputation of the skin to elude a predator’s grasp). Fascinatingly, the spiny mouse completely regenerates the lost skin and regrows cartilage and appendages (nails, hair) with minimal fibrotic response.

A multimodal approach addressing the mechanisms driving spiny’s scarless regeneration may provide novel therapeutic opportunities to treat and prevent skin fibrosis.

In this project, Sofia Ferreira Gonzalez and her team investigate three questions: 1) is the spiny mouse’s scarless regeneration depending on specific cell populations, circulatory factors or a combination thereof, 2) which specific pathways are responsible for the scarless regeneration, and 3) how can the research findings be translated into novel therapeutics to improve skin wound healing in humans?

Skin bacteria lipopeptides: key modulators of keratinocyte immune responses and atopic dermatitis

Grantee: Peter Arkwright, Senior Lecturer, The University of Manchester

Amount: DKK 4,163,557

Grant category: Research Grants in open competition

Year: 2023

Geography: United Kingdom

Dr Peter Arkwright’s project aims to functionally characterize a group of recently discovered anti-inflammatory bacterial substances and investigate their potential therapeutic value in atopic dermatitis.

Staphylococcus aureus is unique in being the only bacterial species that consistently triggers flares in atopic dermatitis (AD). In previous work, also supported by the LEO Foundation, Dr Peter Arkwright, Dr Jo Pennock, and their team at the University of Manchester discovered “Sbi” as the unique factor produced by this bacterium that initiates AD in skin cells. Recently, they have identified factors produced by skin bacteria that completely block Staphylococcus aureus-induced AD, both in the lab and in an eczema mouse model. These factors are small, stable chemicals, made up of both fats and small proteins (lipopeptides).

In a collaboration with Professor Hiroshi Matsuda and Professor Akane Tanaka in Tokyo, Japan, they will apply lipopeptides derived from different bacteria to the skin of mice with AD to determine which are most effective at reducing the clinical dermatitis, itch, and skin damage. They will also explore how these factors work, using cell, protein, and lipid staining techniques. By purifying and characterizing these chemically stable immunosuppressive lipopeptides it is hoped that promising candidates identified here can be taken forward into clinical trials to develop novel therapies for AD.