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Thrombospondin-1-Derived Peptide RFYVVMWK Improves the Adhesive Phenotype of CD34 + Cells from Atherosclerotic Patients with Type 2 Diabetes

Abstract : CD34 + progenitor cells are growing in use for vascular repair. However, in diabetic individuals with cardio-vascular diseases, these cells have dysfunctional engraftment capabilities, which compromise their use for autologous cell therapy. The thrombospondin-1-derived peptide RFYVVMWK has previously been reported to stimulate cell adhesiveness through CD47 and integrin activation pathways. Our aim was to test whether RFYVVMWK preconditioning could modulate CD34 + cell phenotype and enhance its proadhesive properties in diabetic patients. Peripheral blood mononuclear CD34 + cells isolated from 40 atherosclerotic patients with type 2 diabetes (T2D; n = 20) or without (non-T2D; n = 20) were preconditioned with 30 µM RFYVVMWK or truncated peptide RFYVVM. CD34 + cell adhesion was assessed on a vitronectin–collagen matrix and on TNF-a or IL-1b-stimulated HUVEC monolayers. Adhesion receptors, platelet/CD34 + cell conjugates, and cell viability were analyzed by flow cytometry and confocal microscopy. RFYVVMWK increased the adhesion of T2D CD34 + cells by eightfold to the vitronectin–collagen matrix (p < 0.001) corresponding to a threefold increase compared to unstimulated non-T2D CD34 + cells. The peptide induced the formation of platelet/CD34 + conjugates and increased the expression of TSP-1, CD29, CD51/CD61, and CD62P in both T2D and non-T2D cells. However, RFYVVMWK treatment did not affect the viability/apoptosis of CD34 + progenitor cells. In conclusion, priming CD34 + cells with RFYVVMWK may enhance their vascular engraftment during autol-ogous proangiogenic cell therapy.
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Sylvie Cointe, Éric Rhéaume, Catherine Martel, Olivier Blanc-Brude, Evemie Dubé, et al.. Thrombospondin-1-Derived Peptide RFYVVMWK Improves the Adhesive Phenotype of CD34 + Cells from Atherosclerotic Patients with Type 2 Diabetes. Cell Transplantation, Cognizant Communication Corporation, 2017, 26 (2), pp.327 - 337. ⟨10.3727/096368916X693329⟩. ⟨hal-01768677⟩

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