BackgroundThermal injuries affect millions of adults and children worldwide and are associated with high morbidity and mortality. The key determinant for the survival of burns is rapid wound healing. Large wounds exceed intrinsic wound-healing capacities, and the currently available coverage materials are insufficient due to lack of cellularity, availability or immunological rejection.MethodsUsing the surgically debrided tissue, we isolated viable cells from burned skin. The isolated cells cultured in tissue culture dishes and characterized.FindingsWe report here that debrided burned skin, which is routinely excised from patients and otherwise considered medical waste and unconsciously discarded, contains viable, undamaged cells which show characteristics of mesenchymal skin stem cells. Those cells can be extracted, characterized, expanded, and incorporated into created epidermal-dermal substitutes to promote wound healing in immune-compromised mice and Yorkshire pigs without adverse side effects.InterpretationThese findings are of paramount importance and provide an ideal cell source for autologous skin regeneration. Furthermore, this study highlights that skin contains progenitor cells resistant to thermal stress.FundCanadian Institutes of Health Research # 123336. CFI Leader's Opportunity Fund: Project # 25407 National Institutes of Health 2R01GM087285-05A1. EMHSeed: Fund: 500463, A generous donation from Toronto Hydro. Integra© Life Science Company provided the meshed bilayer Integra© for porcine experiments.

Background Multipotent mesenchymal stromal/stem cell (MSC) therapy is under investigation in promising (pre-)clinical trials for wound healing, which is crucial for survival; however, the optimal cell dosage remains unknown. The aim was to investigate the efficacy of different low-to-high MSC dosages incorporated in a biodegradable collagen-based dermal regeneration template (DRT) Integra®. Methods We conducted a porcine study (N = 8 Yorkshire pigs) and seeded between 200 and 2,000,000 cells/cm2 of umbilical cord mesenchymal stromal/stem cells on the DRT and grafted it onto full-thickness burn excised wounds. On day 28, comparisons were made between the different low-to-high cell dose groups, the acellular control, a burn wound, and healthy skin. Result We found that the low dose range between 200 and 40,000 cells/cm2 regenerates the full-thickness burn excised wounds most efficaciously, followed by the middle dose range of 200,000–400,000 cells/cm2 and a high dose of 2,000,000 cells/cm2. The low dose of 40,000 cells/cm2 accelerated reepithelialization, reduced scarring, regenerated epidermal thickness superiorly, enhanced neovascularization, reduced fibrosis, and reduced type 1 and type 2 macrophages compared to other cell dosages and the acellular control. Conclusion This regenerative cell therapy study using MSCs shows efficacy toward a low dose, which changes the paradigm that more cells lead to better wound healing outcome.