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Mar 22, 2023;11 (3):

Adipose-Derived Stromal Cells within a Gelatin Matrix Acquire Enhanced Regenerative and Angiogenic Properties: A Pre-Clinical Study for Application to Chronic Wounds.

Nicolo Costantino Brembilla, Ali Modarressi, Dominik André-Lévigne, Estelle Brioudes, Florian Lanza, Hubert Vuagnat, Stéphane Durual, Laurine Marger, Wolf-Henning Boehncke, Karl-Heinz Krause, Olivier Preynat-Seauve
Author Information
  1. Nicolo Costantino Brembilla: Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1205 Geneva, Switzerland.
  2. Ali Modarressi: Division of Plastic, Reconstructive and Aesthetic Surgery, Geneva University Hospitals, 1205 Geneva, Switzerland.
  3. Dominik André-Lévigne: Division of Plastic, Reconstructive and Aesthetic Surgery, Geneva University Hospitals, 1205 Geneva, Switzerland. ORCID
  4. Estelle Brioudes: Laboratory of Therapy and Stem Cells, Geneva University Hospitals, 1205 Geneva, Switzerland.
  5. Florian Lanza: Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1205 Geneva, Switzerland.
  6. Hubert Vuagnat: Program for Wounds and Wound Healing, Geneva University Hospitals, 1205 Geneva, Switzerland.
  7. Stéphane Durual: Laboratory of Biomaterials, Faculty of Dental Medicine, University of Geneva, 1205 Geneva, Switzerland. ORCID
  8. Laurine Marger: Laboratory of Biomaterials, Faculty of Dental Medicine, University of Geneva, 1205 Geneva, Switzerland.
  9. Wolf-Henning Boehncke: Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1205 Geneva, Switzerland.
  10. Karl-Heinz Krause: Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1205 Geneva, Switzerland. ORCID
  11. Olivier Preynat-Seauve: Laboratory of Therapy and Stem Cells, Geneva University Hospitals, 1205 Geneva, Switzerland.
PMID: 36979966 DOI: 10.3390/biomedicines11030987

Abstract

This study evaluates the influence of a gelatin sponge on adipose-derived stromal cells (ASC). Transcriptomic data revealed that, compared to ASC in a monolayer, a cross-linked porcine gelatin sponge strongly influences the transcriptome of ASC. Wound healing genes were massively regulated, notably with the inflammatory and angiogenic factors. Proteomics on conditioned media showed that gelatin also acted as a concentrator and reservoir of the regenerative ASC secretome. This secretome promoted fibroblast survival and epithelialization, and significantly increased the migration and tubular assembly of endothelial cells within fibronectin. ASC in gelatin on a chick chorioallantoic membrane were more connected to vessels than an empty sponge, confirming an increased angiogenesis in vivo. No tumor formation was observed in immunodeficient nude mice to which an ASC gelatin sponge was transplanted subcutaneously. Finally, ASC in a gelatin sponge prepared from outbred rats accelerated closure and re-vascularization of ischemic wounds in the footpads of rats. In conclusion, we provide here preclinical evidence that a cross-linked porcine gelatin sponge is an optimal carrier to concentrate and increase the regenerative activity of ASC, notably angiogenic. This formulation of ASC represents an optimal, convenient and clinically compliant option for the delivery of ASC on ischemic wounds.

Keywords

adipose stem cells clinical translation mesenchymal stem cells stromal cells

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Grants

  1. no grant number/Fondation pour la recherche sur le diabète
  2. 43333.1/Innosuisse
  3. no grant number/Innogap
  4. no grant number/Fondation Louis Jeantet-Fondation privée des Hopitaux Universitaires de Genève
  5. no grant number/Carigest SA
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