Re-epithelialization of chronic cutaneous ulcers with directly induced epithelial stem cells
July 7
The limited ability of cutaneous progenitor cells to mature into barrier-forming keratinocytes restricts the repair of persistent epidermal defects and contributes to the disability of individuals with progressive dermopathy. Epithelial stem-cell (EpSC) transplantation has emerged as a safe therapeutic approach in such patients, where it holds the promise of restoring the injured integument. However, the mechanisms by which EpSC grafts can promote epidermal regeneration must be carefully assessed before their widespread clinical adoption.
In this study, we used directly induced EpSCs (iEpSCs) as a novel transplantation source to boost re-epithelialization of the skin. Using a mouse model of focal protease-induced epidermal denudation, we found that murine iEpSCs accelerate regeneration by enhancing endogenous keratinocyte progenitor differentiation and by directly giving rise to mature KRT10⁺ suprabasal cells. Transplantation of murine iEpSCs into protease-lesioned ΔNp63⁻/⁻ mice, which exhibit impaired wound closure, confirmed the direct regenerative ability of the grafts and the formation of new exogenous stratified epithelium. We also demonstrated that the xenotransplantation of human iEpSCs (hiEpSCs) is safe in mice, with hiEpSCs persisting long-term in the wound bed where they elaborate human-specific cornified envelopes.
Our findings support the use of epithelial stem-cell therapies to enhance re-epithelialization in chronic cutaneous disorders.