Oral Presentation NZAPS and ANZSOPS Joint Scientific Meeting

Functional analysis of dermal cell populations from keloid scar and healthy human skin (647)

Sarah Meidinger 1 , Anna Brooks 1 , Vaughan Feisst 1 , Michelle Locke 1 2 , Rod Dunbar 1
  1. University of Auckland, Auckland, New Zealand
  2. Department of Plastic and Reconstructive Surgery, Counties Manukau District Health Board, Auckland, New Zealand

Keloid scarring is a fibroproliferative disease characterised by excessive collagen formation and fibroblast proliferation.  Despite some growing knowledge of the molecular mechanisms underlying keloid scarring, the aetiology of keloid scar formation is still unknown and treatment remains challenging.

Invasion into the surrounding skin beyond the original wound site is the key characteristic of keloids discriminating them from hypertrophic scars.  Previously, we found that expression of the invasion marker Twist1 in keloid tissue is increased.  Furthermore, using primary human keloid and healthy skin cultures we were now able to show that keloid fibroblasts retain their augmented potential to invade into a 3D collagen matrix in vitro, while no difference in 2D cell migration was observed between keloid and normal skin fibroblasts.  Subsequently, we developed a 15-colour flow cytometry panel enabling us to analyse the different cell populations in uncultured singe-cell solutions from human keloid tissue and human dermis. This revealed striking differences between the cell populations in keloid and skin. Using fluorescence-activated cell sorting, we are now able to sort the key cell populations from keloid and healthy dermis for next-generation RNA sequencing. This will allow us to discover the functional differences of keloid and skin fibroblasts based on their gene expression and to identify the cell populations responsible for the invasive behaviour in keloid scarring.

Ultimately, this may reveal new pathways and processes involved in keloid formation and invasiveness, which can be targeted for a more effective treatment of keloid scarring.