Dataset Information

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 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.

SUBMITTER: Eylert G

PROVIDER: S-EPMC7831169 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

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

Eylert Gertraud G Dolp Reinhard R Parousis Alexandra A Cheng Richard R Auger Christopher C Holter Magdalena M Lang-Olip Ingrid I Reiner Viola V Kamolz Lars-Peter LP Jeschke Marc G MG

Stem cell research & therapy 20210125 1

<h4>Background</h4>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®.<h4>Methods</h4>We conducted a porcine study (N = 8 Yorkshire pigs) and seeded between 200 and 2,00 ...[more]

PMID: 33494813

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Project description:Translation of multipotent mesenchymal stromal cell (MSC)-based therapies is advancing in human and veterinary medicine. One critical issue is the in vitro culture of MSC before clinical use. Using fetal bovine serum (FBS) as supplement to the basal medium is still the gold standard for cultivation of many cell types including equine MSC. Alternatives are being explored, with substantial success using platelet lysate-supplemented media for human MSC. However, progress lags behind in the veterinary field. The aim of this study was to establish a scalable protocol for equine platelet lysate (ePL) production and to test the ePL in equine MSC culture. Whole blood was harvested into blood collection bags from 20 healthy horses. After checking sample materials for pathogen contamination, samples from 19 animals were included. Platelet concentrates were prepared using a buffy coat method. Platelets, platelet-derived growth factor BB, and transforming growth factor β1 concentrations were increased in the concentrates compared with whole blood or serum (p < 0.05), while white blood cells were reduced (p < 0.05). The concentrates were lysed using freeze/thaw cycles, which eliminated the cells while growth factor concentrations were maintained. Donor age negatively correlated with platelet and growth factor concentrations after processing (p < 0.05). Finally, all lysates were pooled and the ePL was evaluated as culture medium supplement in comparison with FBS, using adipose-derived MSC from four unrelated donor horses. MSC proliferated well in 10% FBS as well as in 10% ePL. However, using 5 or 2.5% ePL entailed highly inconsistent proliferation or loss of proliferation, with significant differences in generation times and confluencies (p < 0.05). MSC expressed the surface antigens CD90, CD44, and CD29, but CD73 and CD105 detection was low in all culture media. Adipogenic and osteogenic differentiation led to similar results in MSC from different culture media. The buffy coat method is useful to produce equine platelet concentrate with increased platelet and reduced white blood cell content in large scales. The ePL obtained supports MSC expansion similar as FBS when used at the same concentration (10%). Further investigations into equine MSC functionality in culture with ePL should follow.

Dataset Information

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

Background

Methods

Result

Conclusion

Publications

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

Similar Datasets

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