Skin regeneration is accelerated by a lower dose of multipotent mesenchymal stromal/stem cells—a paradigm change

Stem Cell Research & Therapy

Viola Reiner¹  Ingrid Lang-Olip¹  Lars-Peter Kamolz²  Richard Cheng³  Magdalena Holter⁴  Alexandra Parousis⁵  Christopher Auger⁵  Gertraud Eylert⁶  Reinhard Dolp⁷  Marc G. Jeschke⁸ 

[1] Division of Cell Biology, Histology, Embryology, Gottfried Schatz Research Center, Medical University of Graz, Graz, Austria;Division of Plastic, Aesthetic, Reconstructive Surgery, Medical University of Graz, Graz, Austria;Coremed- Centre for Regenerative Medicine, Joanneum Research Forschungsgesellschaft mbH, Graz, Austria;Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Canada;Institute of Biostatistics, Medical University of Graz, Graz, Austria;Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Canada;Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Canada;Division of Plastic, Aesthetic, Reconstructive Surgery, Medical University of Graz, Graz, Austria;Institute of Medical Science, University of Toronto, Toronto, ON, Canada;Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Canada;Institute of Medical Science, University of Toronto, Toronto, ON, Canada;Department of Psychiatry, Queen’s University, Kingston, Canada;Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Canada;Institute of Medical Science, University of Toronto, Toronto, ON, Canada;Ross Tilley Burn Centre, Sunnybrook Health Sciences Centre, Toronto, Canada;Division of Plastic and Reconstructive Surgery, Department of Surgery, Faculty of Medicine, University of Toronto, Toronto, Canada;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., M4N 3M5, Toronto, Canada;

关键词: Skin regeneration;    Multipotent mesenchymal stromal/stem cells;    Wound healing;    Cell therapy;    Tissue engineering;    Integra;    Umbilical cord mesenchymal stromal/stem cells;    Experimental surgery;    Skin substitutes;   

DOI  :  10.1186/s13287-020-02131-6

来源: Springer

【 摘 要 】

BackgroundMultipotent 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®.MethodsWe 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.ResultWe 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.ConclusionThis 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.

【 授权许可】

CC BY