Stem Cells for the Ischemic Heart

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Citation
US Cardiology, 2007;4(2):14-8

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The potential of physiological regeneration offered by stem-cell-mediated therapy has captured the imagination of both the public and the scientific community. This is especially true for the cardiovascular and nervous systems, which have long been considered terminally differentiated and post-mitotic with minimal capacity for regeneration and repair.
While the ability of embryonically derived stem cells to generate multiple cell types has long been appreciated, stem cell biology began in the 1950s with the discovery of bone marrow progenitors capable of reconstituting the hematopoietic system. Remarkably, the discovery of endothelial progenitor cells (EPCs)1 capable of homing to sites of ischemia was made only a decade ago, nearly 40 years after the identification of the hematopoietic stem cell. Despite this, the use of EPCs for the treatment of vascular disease has accelerated from pre-clinical studies to clinical application within a short period of time, with resulting debate about the need for further pre-clinical work2 as opposed to acceleration of clinical trials in this field.3
More recently, attention has also been focused on other adult stem cells, including mesenchymal stem cells derived from bone marrow stroma, myoblasts derived from autologous peripheral muscle, and cardiac stem cells grown from myocardial biopsies. Each of these sources lacks the ethical constraints that define the field of embryonic stem cell research, and represents a vigorous area of pre-clinical and clinical research.

Evidence for Progenitor-cell-mediated Repair

The presence of circulating progenitor cells1 capable of differentiating into EPCs and homing to sights of ischemia where they increase neovascularization led to the realization that the state of the vasculature reflects a delicate balance between damage and repair.4 Several creative avenues of research have indicated that stem-cell-mediated repair is an active and ongoing process in both the myocardium and the vasculature. Pre-clinical and human studies demonstrated that foreign bodies implanted in continuity with the vasculature become endothelialized with cells of bone marrow origin.5,6 The potency of progenitor-cell-mediated vascular repair has been demonstrated in both atherosclerotic mice7 and in human radiation injury.8 The presence of gender-mismatched organs after cardiac transplantation has offered investigators the opportunity to probe myocyte generation by cells of host origin.9,10

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