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
Affiliations
Nicolo Costantino Brembilla
Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1205 Geneva, Switzerland
Ali Modarressi
Division of Plastic, Reconstructive and Aesthetic Surgery, Geneva University Hospitals, 1205 Geneva, Switzerland
Dominik André-Lévigne
Division of Plastic, Reconstructive and Aesthetic Surgery, Geneva University Hospitals, 1205 Geneva, Switzerland
Estelle Brioudes
Laboratory of Therapy and Stem Cells, Geneva University Hospitals, 1205 Geneva, Switzerland
Florian Lanza
Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1205 Geneva, Switzerland
Hubert Vuagnat
Program for Wounds and Wound Healing, Geneva University Hospitals, 1205 Geneva, Switzerland
Stéphane Durual
Laboratory of Biomaterials, Faculty of Dental Medicine, University of Geneva, 1205 Geneva, Switzerland
Laurine Marger
Laboratory of Biomaterials, Faculty of Dental Medicine, University of Geneva, 1205 Geneva, Switzerland
Wolf-Henning Boehncke
Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1205 Geneva, Switzerland
Karl-Heinz Krause
Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1205 Geneva, Switzerland
Olivier Preynat-Seauve
Laboratory of Therapy and Stem Cells, Geneva University Hospitals, 1205 Geneva, Switzerland
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.
