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 alphaCD133-glycoprotein (GP)VI as an effective treatment for supporting vascular and myocardial repair mechanisms.
RESULTS: We have generated and characterized a bifunctional molecule (alphaCD133-GPVI) that binds both to the subendothelium of the injured microvasculature and to CD133(+) progenitor cells with high affinity. alphaCD133-GPVI enhances progenitor cell adhesion to extracellular matrix proteins and differentiation into mature endothelial cells. In vivo studies showed that alphaCD133-GPVI favors adhesion of circulating progenitor cells to the injured vessel wall (intravital microscopy). Also, treatment of mice undergoing experimental myocardial infarction with alphaCD133-GPVI-labeled progenitor cells reduces infarction size and preserves myocardial function.
CONCLUSIONS: The bifunctional trapping protein alphaCD133-GPVI represents a novel and promising therapeutic option for limiting heart failure of the ischemic myocardium.