Seeing What We Build—The Need for New Imaging Techniques in Myocardial Regeneration

T he largest experience with stem cell therapy in the heart has been with bone marrow mononuclear cells (BMMCs). Several single-center studies have shown modest, and in some cases transient, increases in ejection fraction (EF) following BMMC injection in patients with reperfused myocardial infarction. While this experience clearly demonstrated the safety of BMMC injection, the imaging readouts used in these phase 1 to 2 studies did not provide a clear “stop or go” signal on which to base further decisions. Several multicenter phase 3 studies of BMMC injection were thus conducted and have been negative, showing no significant changes in EF. A clear need, therefore, exists for more refined imaging tools to guide the development of regenerative therapies in the heart. Successful regeneration in the heart requires the injected cell to be delivered to the correct zone of the myocardium, survive in the host microenvironment, exert beneficial paracrine effects, differentiate, and integrate with the host myocardium. Advanced imaging techniques to characterize many of these processes have been developed (Figure) and several are poised for use in humans. In the current issue of JAHA, Dash and colleagues add to this armamentarium with an elegant approach involving dual-contrast magnetic resonance imaging (MRI) and positron emission tomography (PET) of a reporter probe. The value of this and other advanced imaging approaches is discussed below. Characterization of the Host Myocardium