Skin regeneration is accelerated by a lower dose of multipotent mesenchymal stromal/stem cells—a paradigm change
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 M...
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| Format: | Article |
| Language: | English |
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BMC
2021-01-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13287-020-02131-6 |
| _version_ | 1819330880072581120 |
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| author | Gertraud Eylert Reinhard Dolp Alexandra Parousis Richard Cheng Christopher Auger Magdalena Holter Ingrid Lang-Olip Viola Reiner Lars-Peter Kamolz Marc G. Jeschke |
| author_facet | Gertraud Eylert Reinhard Dolp Alexandra Parousis Richard Cheng Christopher Auger Magdalena Holter Ingrid Lang-Olip Viola Reiner Lars-Peter Kamolz Marc G. Jeschke |
| author_sort | Gertraud Eylert |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-24T14:05:33Z |
| format | Article |
| id | doaj.art-11b74c861cfb49bbb28d2f506981b1e3 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-24T14:05:33Z |
| publishDate | 2021-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-11b74c861cfb49bbb28d2f506981b1e32022-12-21T16:52:21ZengBMCStem Cell Research & Therapy1757-65122021-01-0112111110.1186/s13287-020-02131-6Skin regeneration is accelerated by a lower dose of multipotent mesenchymal stromal/stem cells—a paradigm changeGertraud Eylert0Reinhard Dolp1Alexandra Parousis2Richard Cheng3Christopher Auger4Magdalena Holter5Ingrid Lang-Olip6Viola Reiner7Lars-Peter Kamolz8Marc G. Jeschke9Sunnybrook Research Institute, Sunnybrook Health Sciences CentreSunnybrook Research Institute, Sunnybrook Health Sciences CentreSunnybrook Research Institute, Sunnybrook Health Sciences CentreInstitute of Biomaterials and Biomedical Engineering, University of TorontoSunnybrook Research Institute, Sunnybrook Health Sciences CentreInstitute of Biostatistics, Medical University of GrazDivision of Cell Biology, Histology, Embryology, Gottfried Schatz Research Center, Medical University of GrazDivision of Cell Biology, Histology, Embryology, Gottfried Schatz Research Center, Medical University of GrazDivision of Plastic, Aesthetic, Reconstructive Surgery, Medical University of GrazSunnybrook Research Institute, Sunnybrook Health Sciences CentreAbstract 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.https://doi.org/10.1186/s13287-020-02131-6Skin regenerationMultipotent mesenchymal stromal/stem cellsWound healingCell therapyTissue engineeringIntegra |
| spellingShingle | Gertraud Eylert Reinhard Dolp Alexandra Parousis Richard Cheng Christopher Auger Magdalena Holter Ingrid Lang-Olip Viola Reiner Lars-Peter Kamolz Marc G. Jeschke Skin regeneration is accelerated by a lower dose of multipotent mesenchymal stromal/stem cells—a paradigm change Stem Cell Research & Therapy Skin regeneration Multipotent mesenchymal stromal/stem cells Wound healing Cell therapy Tissue engineering Integra |
| title | Skin regeneration is accelerated by a lower dose of multipotent mesenchymal stromal/stem cells—a paradigm change |
| title_full | Skin regeneration is accelerated by a lower dose of multipotent mesenchymal stromal/stem cells—a paradigm change |
| title_fullStr | Skin regeneration is accelerated by a lower dose of multipotent mesenchymal stromal/stem cells—a paradigm change |
| title_full_unstemmed | Skin regeneration is accelerated by a lower dose of multipotent mesenchymal stromal/stem cells—a paradigm change |
| title_short | Skin regeneration is accelerated by a lower dose of multipotent mesenchymal stromal/stem cells—a paradigm change |
| title_sort | skin regeneration is accelerated by a lower dose of multipotent mesenchymal stromal stem cells a paradigm change |
| topic | Skin regeneration Multipotent mesenchymal stromal/stem cells Wound healing Cell therapy Tissue engineering Integra |
| url | https://doi.org/10.1186/s13287-020-02131-6 |
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