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Key Concepts

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  • There are an estimated 5.8 million people in the United States with heart failure.1

  • Stem cell therapy for the heart represents a novel method by which dysfunctional cardiac tissue might be repaired or replaced, thereby alleviating heart failure and decreasing or eliminating life-threatening arrhythmias.

  • Potential sources of stem cell therapy for the heart include the bone marrow, circulating progenitor cells, embryonic stem cells, and the heart itself.

  • Multiple modalities exist for delivery of stem cell therapy to the heart, including traditional and minimally invasive surgical methods as well as intravenous and percutaneous catheter-based techniques.

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Introduction/Background

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The heart was once thought to be a terminally differentiated organ, with no cell turnover or repair; the cardiac myocytes at the time of early adulthood were all the cells a person would ever have. It was for this reason that myocardial infarction (MI) was thought to be such a devastating event, as there was no native ability to repair or replace damaged heart tissue. This understanding began to change in the 1990s, when investigators first reported the presence of cardiac myocytes in various stages of cell division, found during histologic analysis of myocardial tissue.2 Since that time it was learned that the heart does have the capacity for cellular repair, both from stem cells resident in the heart, and from so-called “circulating” progenitor cells, which, following release from the bone marrow, may traffic to and enter heart tissue to effect repair.35 This endogenous repair system appears to have the capacity to handle routine cellular turnover, that is, normal “wear and tear” on the heart, but becomes overwhelmed in the setting of a sudden large insult, such as a MI, with the default fibroblast scar formation. With the discovery of the capacity for cellular repair of the heart, interest in augmenting or optimizing this system to the point that the damaged and failing heart could be biologically repaired has grown. For example, although the small number of resident cardiac stem cells (CSCs) might be insufficient to repair the damage of a large infarction, removal and expansion of these cells in ex vivo tissue culture might generate sufficient numbers of cells to result in a therapeutic benefit.

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The interest in cell therapy is driven primarily by the nearly 6 million Americans with heart failure,1 as well as millions of others throughout the world, many of whom, despite optimal medical therapy, suffer significant morbidity and mortality from their condition. In many cases, temporary mechanical support or heart transplantation is necessary, but supply constraints and large expense limit availability. Thus, the great hope for cellular therapy for the heart is that end-stage heart failure could be eliminated by preventing or reversing the deleterious remodeling that occur following significant injury to the heart. Although such benefits are reported in animal models, clinical cell therapy for the heart remains in its infancy, and numerous questions ...

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