The recombinant bifunctional protein αCD133-GPVI promotes repair of the infarcted myocardium in mice.

Summary. Background:  Bone-marrow-derived progenitor cells are important in myocardial repair mechanisms following prolonged ischemia. Cell-based therapy of diseased myocardium is limited by a low level of tissue engraftment. Objectives:  The aim of this study was the development of the bifunctional protein αCD133–glycoprotein (GP)VI as an effective treatment for supporting vascular and myocardial repair mechanisms. Results:  We have generated and characterized a bifunctional molecule (αCD133–GPVI) that binds both to the subendothelium of the injured microvasculature and to CD133+ progenitor cells with high affinity. αCD133–GPVI enhances progenitor cell adhesion to extracellular matrix proteins and differentiation into mature endothelial cells. In vivo studies showed that αCD133–GPVI favors adhesion of circulating progenitor cells to the injured vessel wall (intravital microscopy). Also, treatment of mice undergoing experimental myocardial infarction with αCD133–GPVI-labeled progenitor cells reduces infarction size and preserves myocardial function. Conclusions:  The bifunctional trapping protein αCD133–GPVI represents a novel and promising therapeutic option for limiting heart failure of the ischemic myocardium.