Cardiologists battle our nation’s number one killer: heart disease. Bone marrow transplant and cancer have their own challenges and carry grave connotations, but cardiovascular (CV) disease causes most of the deaths and disabilities in the US, claiming nearly one million lives each year.¹ The cost of cardiac care is estimated to approach $400 billion per year and, with an aging US population and epidemics in diabetes, metabolic syndrome, and obesity, the incidence of CV diseases will increase.² Moreover, with improved survival rates after acute ischemic syndromes, the number of patients reaching the later stages of ischemic heart disease (e.g. left ventricular dysfunction, heart failure, arrhythmias, and premature death) will also increase.

Important strides have been made in optimizing medical management with antiplatelet agents, beta-blockers, statins, renin–angiotensin inhibitors, aldosterone inhibitors, blood-pressure reduction, and smoking cessation. However, additional pharmacotherapeutic manipulations are likely to bring only modest increases in benefit, as reflected by the pharmaceutical industry’s decreasing emphasis on this area. These considerations, plus the well-recognized limitations in mechanical hearts, heart transplantation, implantable defibrillators, restriction devices, and mitral valve repair, have spurred interest in novel approaches for left ventricular dysfunction.

Pre-clinical Evidence of Cell Therapy for Cardiovascular Disease

Numerous animal studies have demonstrated that transplantation of bone-marrow-derived cells improves cardiac function in settings of acute myocardial infarction (MI) and ischemic cardiomyopathy.³ Whole bone marrow (autologous and allogeneic), CD34+ cells, CD133+ cells, mesenchymal stem cells (MSC) (autologous and allogeneic), and endothelial progenitor cells represent several transplanted marrow elements. Moreover, various marrow-to-myocardium transplant techniques have been used, including intracoronary infusions, intraventricular myocardial injections, and extraventricular myocardial injections, via a surgical approach. Each technique has resulted in benefit to some degree.

Where the situation gets controversial is mechanism. How do marrowderived cells assist in myocardial regeneration? Initially, there was intense interest in direct transdifferentiation of hematopoietic cells into myocardium. Can adult marrow cells turn into heart muscle? Studies by Orlic et al.⁴ and Yoon et al.⁵ found evidence of bone marrow plasticity in rodent hearts, but further testing failed to show transdifferentiation of adult marrow cells into cardiomyocytes.^6–8 A second possibility is paracrine regulation.