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 (TIID; n=20) or without (NonTIID; n=20) type II 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 TNFa or IL-1b-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 TIID CD34+ cells to the vitronectin-collagen matrix (p <0.001) corresponding to a 3-fold increase compared to unstimulated NonTIID CD34+ cells. The peptide induced the formation of platelet/CD34+ conjugates and increased the expression of TSP-1, CD29, CD51, and CD62P in both TIID and NonTIID cells. However, RFYVVMWK treatment did not affect the viability/apoptosis of CD34+ progenitor cells.

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

Disclosures

No relevant conflicts of interest to declare.

Author notes

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Asterisk with author names denotes non-ASH members.