The role of fucosylation in the promotion of endothelial progenitor cells in neovascularization and bone repair

Abstract

Bone marrow-derived endothelial progenitor cells (EPCs) are being tested as a therapy to treat a variety of ischemic diseases. Poor homing to targeted tissues is one of the major factors limiting the therapeutic efficacy of EPCs. Here, we show that human cord blood-derived EPCs expressed little sialyl Lewis X (sLe(x)) antigen that is necessary for selectin-mediated cell-cell interactions. Expression of α1,3-fucosyltransferase VI (FucT VI) in the EPCs enhanced sLe(x) synthesis, E- and P-selectin-binding, and EPC adhesion to tumor necrosis factor-α-stimulated human umbilical vein endothelial cells in culture. In a mouse model of hind limb ischemia, in which EPCs were injected intravenously, FucT VI expression increased EPC homing, neovascularization, and blood flow in ischemic muscles. In another mouse model of femoral fracture, FucT VI-expressing EPCs were more efficient than control EPCs in targeting to peri-fracture tissues to enhance angiogenesis, blood flow and bone repair. These results indicate that fucosylated EPCs may be used to as an improved cellular source to treat ischemic diseases.

Keywords: Angiogenesis; Bone repair; Endothelial progenitor cells; Fucosylation; Ischemic disease; Selectins.