GMP-compliant sponge-like dressing containing MSC lyo-secretome: Proteomic network of healing in a murine wound model
| Autor: | Marta Nardini, Sara Perteghella, Maria Luisa Torre, Pierluigi Mauri, Maddalena Mastrogiacomo, Dario Di Silvestre, Rossana Rossi, Marzio Sorlini, Giorgio Marrubini, Luca Mastracci, Giovanni Sesana, Elia Bari, Federica Grillo, Pietro Grisoli |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
Proteomics Decorin Alginates Pharmaceutical Science Tenascin Wound healing 02 engineering and technology 030226 pharmacology & pharmacy Fibroblast migration 03 medical and health sciences Mice MSC-secretome 0302 clinical medicine Healing proteomic network MSC-extracellular vesicles Murine model Wound dressing In vivo medicine Animals biology Chemistry Mesenchymal stem cell Granulation tissue General Medicine 021001 nanoscience & nanotechnology Bandages Gelatin Sponge Absorbable Microvesicles Cell biology Disease Models Animal medicine.anatomical_structure biology.protein 0210 nano-technology Biotechnology |
| Popis: | Chronic wounds account for 3% of total healthcare expenditure of developed countries; thus, innovative therapies, including Mesenchymal Stem Cells (MSCs) end their exosomes are increasingly considered, even if the activity depends on the whole secretome, made of both soluble proteins and extracellular vesicles. In this work, we prove for the first time the in vivo activity of the whole secretome formulated in a sponge-like alginate wound dressing to obtain the controlled release of bioactive substances. The product has been prepared in a public GMP-compliant facility by a scalable process; based on the murine model, treated wounds healed faster than controls without complications or infections. The treatment induced a higher acute inflammatory process in a short time and sustained the proliferative phase by accelerating fibroblast migration, granulation tissue formation, neovascularization and collagen deposition. The efficacy was substantially supported by the agreement between histological and proteomic findings. In addition to functional modules related to proteolysis, complement and coagulation cascades, protein folding and ECM remodeling, in treated skin, emerged the role of specific wound healing related proteins, including Tenascin (Tnc), Decorin (Dcn) and Epidermal growth factor receptor (EGFR). Of note, Decorin and Tenascin were also components of secretome, and network analysis suggests a potential role in regulating EGFR. Although further experiments will be necessary to characterize better the molecular keys induced by treatment, overall, our results confirm the whole secretome efficacy as novel "cell-free therapy". Also, sponge-like topical dressing containing the whole secretome, GMP- compliant and "ready-off-the-shelf", may represent a relevant point to facilitate its translation into the clinic. |
| Databáze: | OpenAIRE |
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