IL-1β-primed Mesenchymal Stromal Cells improve epidermal substitute engraftment and wound healing via MMPs and TGF-β1

Abstract Since the 1980s, deep and extensive skin wounds and burns are treated with autologous Split-Thickness Skin Grafts, or Cultured Epidermal Autografts (CEAs) when donor sites are limited. However, the clinical use of CEAs often remains unsatisfactory due to poor engraftment rates, altered wound healing and reduced skin functionality. In the past few decades, Mesenchymal Stromal Cells (MSCs) have raised much attention due to their anti-inflammatory, pro-trophic and pro-remodeling capacities. More specifically, gingival MSCs have been shown to possess enhanced wound healing properties compared to other tissue sources. Growing pieces of evidence have also indicated that MSC priming could potentiate therapeutic effects in diverse in vitro and in vivo models of skin trauma. In the present study, we found that, IL-1β-primed gingival MSCs (IL-MSCs) promoted cell migration, dermal-epidermal junction formation and inflammation reduction in vitro, as well as improved epidermal substitute engraftment in vivo. IL-MSCs had different secretory profiles from naive gingival MSCs (NV-MSCs), characterized by an overexpression of TGF-β and MMP pathway agonists. Eventually, MMP-1, MMP-9 and TGF-β1 appeared to be critically involved in IL-MSC mechanisms of action.