Heart failure continues to be one of the leading causes of morbidity and mortality worldwide. Myocardial infarction is the primary causative agent of chronic heart failure resulting in cardiomyocyte necrosis and the subsequent formation of fibrotic scar tissue. Current pharmacological and non-pharmacological therapies focus on managing symptoms of heart failure yet remain unable to reverse the underlying pathology. Heart transplantation usually cannot be relied on, as there is a major discrepancy between the availability of donors and recipients. As a result, heart failure carries a poor prognosis and high mortality rate. As the heart lacks significant endogenous regeneration potential, novel therapeutic approaches have incorporated the use of stem cells as a vehicle to treat heart failure as they possess the ability to self-renew and differentiate into multiple cell lineages and tissues. This review will discuss past, present, and future clinical trials, factors that influence stem cell therapy outcomes as well as ethical and safety considerations. Preclinical and clinical studies have shown a wide spectrum of outcomes when applying stem cells to improve cardiac function. This may reflect the infancy of clinical trials and the limited knowledge on the optimal cell type, dosing, route of administration, patient parameters and other important variables that contribute to successful stem cell therapy. Nonetheless, the field of stem cell therapeutics continues to advance at an unprecedented pace. We remain cautiously optimistic that stem cells will play a role in heart failure management in years to come.

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