Incubation Of Porcine Urinary Bladder Matrix Of Endothelial Cells And Keratinocytes From Diabetic Patients Restores A Non-diabetic Phenotype
John Paige1, David Lightell, Jr.2, Jace Landry1, T. Cooper Woods2.
1LSU Health New Orleans School of Medicine, New Orleans, LA, USA, 2Tulane University School of Medicine, New Orleans, LA, USA.
Background: Delayed wound healing is common in diabetic patients. Appropriate wound healing requires coordinated proliferation and migration of endothelial cells and keratinocytes. Porcine urinary bladder matrix (UBM) has been demonstrated to facilitate wound healing and decrease times to closure of diabetic foot ulcers. This study examined the impact of incubation with UBM on the phenotype of keratinocytes and endothelial cells isolated from diabetic patients. Methods: Human keratinocytes and dermal endothelial cells isolated from non-diabetic (n=3) and diabetic (n=3) donors were incubated with and without UBM powder. Total RNA was obtained from the samples and RNA-Seq analysis was performed to identify changes in RNA expression associated with exposure to UBM. Results: Principle component analysis (PCA) and hierarchical clustering demonstrated that while diabetic and non-diabetic cells initially exhibited very different RNA expression profiles, these differences were minimized following incubation with UBM. Keratinocytes incubated in UBM exhibited an increase in markers of activation, keratin 16 (2.50 ± 0.85, p < 0.05), keratin 6B (2.07 ± 0.79, p < 0.05), and keratin 6C (2.51 ± 0.90, p < 0.05) and down regulation of several growth factors associated with the inflammatory stage of wound healing, including Transforming Growth Factor-β1 (0.12 ± 0.04, p < 0.05), Connective Tissue Growth Factor (0.04 ± 0.004, p < 0.05), and Fibroblast Growth Factor 2 (0.09 ± 0.02, p < 0.05). In endothelial cells, UBM exposure was associated with decreased adhesion molecules, Intercellular Adhesion Molecule-1 (0.001 ± 0.0001, p < 0.05) and Platelet Endothelial Cell Adhesion Molecule-2 (0.01 ± 0.001, p < 0.05)and increased expression of several members of the S100A family (p < 0.05). Conclusion: These data suggest that exposure with UBM may restore normal cellular function in diabetic endothelial cells and keratinocytes in wounds. Larger studies are needed to evaluate more fully the effects of UBM on diabetic wound healing..
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