Cortical Bone Stem Cells Administered at Reperfusion Attenuate Remote Zone Myocyte Remodeling
This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
Heart failure arises from intrinsic diseases of cardiac muscle or idiopathic dilated cardiomyopathy as well as consequences of coronary artery disease after acute myocardial infarction and chronic ischemia. In patients with ST-segment–elevation myocardial infarction (MI) from a coronary thrombus, immediate reperfusion is the most effective therapy to prevent the loss of myocytes. The routine use of β-blockers, angiotensin inhibition therapy, and spironolactone blocks neurohormonal activation and prevents subsequent left ventricular (LV) remodeling. Stem cell therapy has emerged as an adjunctive approach to further attenuate postinfarction remodeling by stimulating myocyte proliferation and mitigating myocyte loss arising from within and outside of the infarct region. Despite favorable preclinical and early clinical studies in humans using bone marrow mononuclear cells, meta analyses of completed trials have failed to demonstrate a significant impact on clinical outcomes and LV function.1 Because substantial myocyte loss occurs during the first few days after infarction, the lack of efficacy may reflect delays in administering therapy that arise from synthesizing autologous cell products after the event. This and the increasing recognition of the role that paracrine effects play led to interest in allogeneic cells, such as cardiosphere-derived cells (CDCs) and mesenchymal stem cells (MSCs). These are relatively immune privileged and can be administered at the time of percutaneous coronary intervention and reperfusion. Cortical bone stem cells (CBSCs) are a particularly proliferative mesenchymal cell subtype2 that, in vitro, have characteristics similar to murine cKit+/Sca1+ cells and can to some extent transdifferentiate into cardiac myocytes.3 Enriching the cKit+ CBSC population could potentially provide an allogeneic cell therapy platform similar to cardiac stem cells (CSCs) without the need for a myocardial biopsy. Completed studies in nonreperfused murine infarct models have demonstrated that they attenuate postinfarction remodeling.3
Article, see p 1263
In this issue of …