Gertraud Eylert1,2,3, Reinhard Dolp1,3,4, Alexandra Parousis1, Richard Cheng5, Christopher Auger1, Magdalena Holter6, Ingrid Lang-Olip7, Viola Reiner7, Lars-Peter Kamolz2,8, Marc G Jeschke9,10,11,12,13. 1. Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Canada. 2. Division of Plastic, Aesthetic, Reconstructive Surgery, Medical University of Graz, Graz, Austria. 3. Institute of Medical Science, University of Toronto, Toronto, ON, Canada. 4. Department of Psychiatry, Queen's University, Kingston, Canada. 5. Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Canada. 6. Institute of Biostatistics, Medical University of Graz, Graz, Austria. 7. Division of Cell Biology, Histology, Embryology, Gottfried Schatz Research Center, Medical University of Graz, Graz, Austria. 8. Coremed- Centre for Regenerative Medicine, Joanneum Research Forschungsgesellschaft mbH, Graz, Austria. 9. Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Canada. Marc.Jeschke@sunnybrook.ca. 10. Institute of Medical Science, University of Toronto, Toronto, ON, Canada. Marc.Jeschke@sunnybrook.ca. 11. Ross Tilley Burn Centre, Sunnybrook Health Sciences Centre, Toronto, Canada. Marc.Jeschke@sunnybrook.ca. 12. Division of Plastic and Reconstructive Surgery, Department of Surgery, Faculty of Medicine, University of Toronto, Toronto, Canada. Marc.Jeschke@sunnybrook.ca. 13. Department of Surgery, Division of Plastic Surgery, Department of Immunology, Director Ross Tilley Burn Centre, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, 2075 Bayview Ave., Toronto, M4N 3M5, Canada. Marc.Jeschke@sunnybrook.ca.
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/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.
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.
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