Heart failure is a significant source of morbidity and mortality around the world. Recently,
cell therapy has garnered much attention as a means for improving cardiac function after injury. Despite
years of study, a growing list of failed efficacy trials has led many to question the translatability
of preclinical work. In this review, we critically evaluate the evidence supporting the need for transplanted
cells to engraft and persist in the impaired heart (the cell engraftment hypothesis). We explore
how the complex interplay between cell retention, persistence and paracrine potency explains many of
the recent cell treatment outcomes. Through this discussion, we outline a framework to understand how
future approaches will optimize and personalize the methods, payloads and timing of cardiac cell delivery
for the millions of patients worldwide suffering from heart failure.
Keywords: Stem cell, heart failure, engraftment, cytokine, exosome, differentiation.
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