Stem Cell Therapy and Regenerative Medicine: Cardiac Repair

The clinical need for new therapies for cardiac repair is obvious and particularly relevant to conditions such as heart failure, ischemic cardiomyopathy, and myocardial infarction (MI). Studies using cell therapies in humans with these conditions are performed rapidly after demonstration of efficacy in animal models. This progression has occurred without a clear understanding of the basic science underpinning this technology.

 Substantial progress has been made in understanding the potential of cell therapy in cardiovascular disease, but there is still a dearth of crucial information, such as the optimal cell type; mode of processing of cells; and dose, mode, and timing of cell delivery. Most studies have used unfractionated or mononuclear bone marrow cells that were injected via catheters into the infarct-related artery within a few days of the MI. These limitations may be responsible for the inconsistent outcomes reported in human studies. It would appear that, in patients with preserved LVEF after MI, stem cell therapy provides no benefit, but those with large MIs and reduced LVEF may benefit. However, the modest efficacy outcomes are probably related to poor engraftment and retention of the injected cells in myocardium, issues that require additional preclinical experiments. Future studies should focus on patients with the largest infarcts and on methods to enhance engraftment of stem cells at the site of injury.

Most patients enrolled in clinical studies of cardiac repair using a stem cell therapy center have had an MI. The clinical rationale for stem cell therapy for MI is to restore cardiac function and thus prevent left ventricular remodeling that can lead to heart failure. Gersh et al1 report that these studies have demonstrated safety, with only modest improvement in cardiac function. Recent meta-analyses have confirmed modest improvements in left ventricular ejection fraction (LVEF) associated with cell therapy after MI.3, 4 The findings of some studies have suggested that patients with the most severe MIs benefit the most, but a recent publication of the REGENT trial has shown no benefit from cell therapy, even in patients with LVEF of less than 40%.5 The REGENT trial may have been limited by inadequate power to detect a difference between the study and control groups, but contradictory results have also been observed in previous studies of intracoronary delivery of bone marrow-derived progenitor cells (ASTAMI and REPAIR-AMI).6, 7

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