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Decellularized silk fibroin scaffold primed with adipose mesenchymal stromal cells improves wound healing in diabetic mice
- Source :
- Stem Cell Research & Therapy
- Publication Year :
- 2014
- Publisher :
- BioMed Central, 2014.
-
Abstract
- Introduction: Silk fibroin (SF) scaffolds have been shown to be a suitable substrate for tissue engineering and to improve tissue regeneration when cellularized with mesenchymal stromal cells (MSCs). We here demonstrate, for the first time, that electrospun nanofibrous SF patches cellularized with human adipose-derived MSCs (Ad-MSCs-SF), or decellularized (D-Ad-MSCs-SF), are effective in the treatment of skin wounds, improving skin regeneration in db/db diabetic mice. Methods: The conformational and structural analyses of SF and D-Ad-MSCs-SF patches were performed by scanning electron microscopy, confocal microscopy, Fourier transform infrared spectroscopy and differential scanning calorimetry. Wounds were performed by a 5 mm punch biopsy tool on the mouse’s back. Ad-MSCs-SF and D-Ad-MSCs-SF patches were transplanted and the efficacy of treatments was assessed by measuring the wound closure area, by histological examination and by gene expression profile. We further investigated the in vitro angiogenic properties of Ad-MSCs-SF and D-Ad-MSCs-SF patches by affecting migration of human umbilical vein endothelial cells (HUVECs), keratinocytes (KCs) and dermal fibroblasts (DFs), through the aortic ring assay and, finally, by evaluating the release of angiogenic factors. Results: We found that Ad-MSCs adhere and grow on SF, maintaining their phenotypic mesenchymal profile and differentiation capacity. Conformational and structural analyses on SF and D-Ad-MSCs-SF samples, showed that sterilization, decellularization, freezing and storing did not affect the SF structure. When grafted in wounds of diabetic mice, both Ad-MSCs-SF and D-Ad-MSCs-SF significantly improved tissue regeneration, reducing the wound area respectively by 40% and 35%, within three days, completing the process in around 10 days compared to 15–17 days of controls. RT 2 gene profile analysis of the wounds treated with Ad-MSCs-SF and D-Ad-MSCs-SF showed an increment of genes involved in angiogenesis and matrix remodeling. Finally, Ad-MSCs-SF and D-Ad-MSCs-SF co-cultured with HUVECs, DFs and KCs, preferentially enhanced the HUVECs’ migration and the release of angiogenic factors stimulating microvessel outgrowth in the aortic ring assay. Conclusions: Our results highlight for the first time that D-Ad-MSCs-SF patches are almost as effective as Ad-MSCs-SF patches in the treatment of diabetic wounds, acting through a complex mechanism that involves stimulation of angiogenesis. Our data suggest a potential use of D-Ad-MSCs-SF patches in chronic diabetic ulcers in humans.
- Subjects :
- Keratinocytes
Angiogenesis
Medicine (miscellaneous)
Fibroin
Adipose tissue
Mice, Obese
Neovascularization, Physiologic
Mesenchymal Stem Cell Transplantation
Biochemistry, Genetics and Molecular Biology (miscellaneous)
Rats, Sprague-Dawley
Mice
Tissue engineering
Re-Epithelialization
Cell Movement
Cell Adhesion
Human Umbilical Vein Endothelial Cells
Animals
Humans
Cells, Cultured
Cell Proliferation
Decellularization
Tissue Scaffolds
Chemistry
Regeneration (biology)
Research
Mesenchymal stem cell
Mesenchymal Stem Cells
Cell Biology
Anatomy
Fibroblasts
Cell biology
Rats
Adipose Tissue
Molecular Medicine
Receptors, Leptin
Wound healing
Fibroins
Subjects
Details
- Language :
- English
- ISSN :
- 17576512
- Volume :
- 5
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Stem Cell Research & Therapy
- Accession number :
- edsair.doi.dedup.....e14d3026a7f599d00780a8a8b3fb6474