Skin regeneration is accelerated by a lower dose of multipotent mesenchymal stromal/stem cells—a paradigm change
Gertraud Eylert, R. Dölp, Alexandra Parousis, Richard Cheng, Christopher Auger, Magdalena Holter, Ingrid Lang, Viola Reiner, Lars‐Peter Kamolz, Marc G. Jeschke
Abstract
Abstract 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/cm 2 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/cm 2 regenerates the full-thickness burn excised wounds most efficaciously, followed by the middle dose range of 200,000–400,000 cells/cm 2 and a high dose of 2,000,000 cells/cm 2 . The low dose of 40,000 cells/cm 2 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.