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Thrombospondin-1-derived peptide RFYVVMWK improves the adhesive phenotype of CD34sup+/sup cells from atherosclerotic patients with type 2 diabetes

Abstract :

Background: CD34(+) progenitor cells are growingly used for vascular repair. However, in diabetic individuals with cardiovascular 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.

Objectives: Our aim was to test whether RFYVVMWK preconditioning could modulate CD34(+) cells phenotype and enhance its pro-adhesive properties in diabetic patients.

Patients/methods: Peripheral blood mononuclear CD34(+) cells isolated from 40 atherosclerotic patients with (T2D; n=20) or without (NonT2D; n=20) type 2 diabetes were pre-conditioned with 30µM of RFYVVMWK (or truncated peptide RFYVVM. CD34(+) cell adhesion was assessed on a vitronectin-collagen matrix and on a TNFα or IL-1β- stimulated HUVEC monolayers. Adhesion receptors, platelet/CD34(+) cell conjugates, and cell viability were analyzed by flow cytometry and confocal microscopy.

Results: RFYVVMWK increased by 8 folds the adhesion of T2D CD34(+) cells to the vitronectin-collagen matrix (p <0.001) corresponding to a 3-fold increase compared to unstimulated NonT2D 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 NonT2D cells. However, RFYVVMWK treatment did not affect the viability/apoptosis of CD34(+) progenitor cells.

Conclusions: Priming CD34(+) cells with RFYVVMWK may enhance their vascular engraftment during autologous pro-angiogenic cell therapy.

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https://hal-amu.archives-ouvertes.fr/hal-01454820
Contributor : Françoise Dignat-George <>
Submitted on : Friday, February 3, 2017 - 9:31:45 AM
Last modification on : Wednesday, August 19, 2020 - 12:08:22 PM

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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 CD34sup+/sup cells from atherosclerotic patients with type 2 diabetes. Cell Transplantation, Cognizant Communication Corporation, 2016, ⟨10.3727/096368916X693329⟩. ⟨hal-01454820⟩

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