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Cortical bone-derived stem cells: a novel class of cells for myocardial protection.

Acute myocardial infarction (MI) remains a significant cause of mortality and morbidity worldwide, despite steady advances in our understanding and treatment of coronary heart disease.1 After MI, lost myocardium is replaced with scar tissue, leading to left ventricular (LV) remodeling and ultimately culminating with ischemic cardiomyopathy and congestive heart failure. We now know that the adult heart is not a postmitotic organ lacking capacity for self-renewal after injury. This paradigm shift occurred after identification of stem cell niches in the adult heart and isolation of cardiac progenitor cells, including c-kit+ cardiac stem cells (CSCs), side population cells, and cardiospheres.2–7 However, the endogenous proliferation of cardiac progenitor cells after MI is inadequate for full replacement of the large number of depleted cells.8 To overcome this problem, extensive efforts have been made in developing cell-based therapies to promote tissue repair by introduction of exogenous cells, such as bone marrow–derived mononuclear cells (BM-MNCs), bone marrow–derived mesenchymal stem cells (BM-MSCs), adipose tissue–derived mesenchymal stem cells, CD34+ stem cells, c-kit+ CSCs, and cardiosphere-derived cells, as evidenced by recent clinical trials.9–16

Article, see p 539

For now, the BM-MNCs are the most widely used source of cells in cardiovascular regenerative therapy trials. However, despite some successful early-stage clinical trials, several recent studies involving the use of BM-MNCs have not been overwhelmingly positive. For example, in the placebo-controlled Transplantation in Myocardial Infarction Evaluation (TIME) trial in which investigators assessed whether differential timing of BM-MNCs delivery affected LV ejection fraction (LVEF) after acute MI (3–7 days), no significant differences between the BM-MNCs and placebo groups were observed for either primary or secondary end points.17 In fact, the TIME trial was the third study in a series of studies (Late-TIME,18 Effectiveness of Stem Cell Treatment for …