Cardiac Repair With Autologous Bone Marrow Stem Cells

In a small town in northern Montana, a 64-year-old retired nurse, physically active, but moderately obese, had been having episodes of angina related to physical stress for 1 week. When a more severe attack of angina persisted, she immediately chewed and swallowed 325 mg of aspirin and called her family practitioner, who arrived at her home promptly and administered 5 mg of intravenous morphine sulfate. The chest pain was alleviated soon after, and she was given 20 mg of atorvastatin and then transported by medical air ambulance 150 miles to a tertiary hospital equipped to care for acute coronary events. The admitting electrocardiogram revealed an acute ST elevation anterolateral infarction with several multifocal ventricular premature beats and a heart rate of 100 beats/minute. The duration of the acute myocardial infarction (MI) (from onset of chest pain to arrival at the hospital emergency department) was estimated to be 3½ hours. Primary percutaneous transluminal angioplasty and drug eluting stenting of a proximal left anterior descending artery thrombotic occlusion was successfully performed. The cardiologist in attendance was a member of a national team investigating the therapeutic benefits of transplanting bone marrow–derived endothelial progenitor cells (EPCs) into the myocardium of patients with an acute MI. The patient agreed to participate in this investigation.1. g. all of the aboveEmerging research in cardiac therapy is destined to enhance the rate of survival in cardiac patients. The current therapeutic options continue to be effective and are not replaced by the recent introduction of stem cells in cardiac treatment. Current therapy in acute MI is aimed at limiting the volume of injured and dead myocardium. In contrast, stem cell therapy adds new myocardium to replace infarcted muscle.Pharmacological therapies timely administered have favorable effects on reducing complications and prognosis in acute MI and heart failure. Early cardiac catheterization of the culprit artery and the use of drug-eluting stents have often replaced coronary bypass surgery, with time being the critical factor in making a decision. Mechanical assist devices are effective in maintaining blood pressure and supporting the left ventricle in refractory congestive heart failure. Cardiac transplantation is a last resort when therapy has failed. Currently cellular cardiomyoplasty is evolving as effective therapy following an acute MI. Adult bone marrow contains EPCs, which are mobilized from the bone marrow following endogenous stimuli, enter the peripheral circulation, and incorporate into sites of injury and repair. EPCs are the origin of cell types that can differentiate into arterial wall cells (endothelium and small muscle cells) and myocardial cells (cardiomyocytes). Bone marrow–derived EPCs are harvested from the patient’s own bone marrow and can be delivered to the infarcted area of the myocardium by several methods.2. a. cellular replacement of injured myocardium and blood vessels b. directing differentiated cells to specific organ targetsA wide variety of potential donor cells arise postnatally, not only from stem cells, but also from the adult bone marrow, circulating mononuclear cells, and cord blood. These vascular EPCs have endothelium-specific cell-surface marker characteristics and endothelial properties.1,2 Following endogenous stimuli, EPCs mobilize from the bone marrow to the peripheral circulation and are incorporated into sites of injury and repair.3. c. depletion and obsolescence of reparative cells d. by a disequilibrium between vascular injury and repairAtherosclerosis is attributed to chronic vascular injury, which occurs with hyperlipidemia, hypertension, or tobacco use. These CV risk factors contribute to atherogenesis by inducing endothelial cell injury, leading to endothelial dysfunction. Advancing age is a known additional factor in the incidence of atherosclerosis. Subsequent endothelial cell damage, which occurs by direct injury or incurred dysfunction, is the stimulus for the development of the atherosclerotic plaque.3 In aging, there is exhaustion or obsolescence of cells that are responsible for repair and rejuvenation of CV tissues. Continuous endothelial damage or dysfunction leads to depletion or exhaustion of a presumed finite supply of EPCs. In studies of patients with CV disease, there was an inverse correlation between the number of circulating EPCs and CV risk factors. The number of EPCs was also associated with the level of endothelial function (measured by brachial artery reactivity).4 As a result of aging, the supply of bone marrow cells capable of vascular and myocardial repair is probably exhausted, which would result in a disequilibrium between vascular injury and vascular repair, promoting atherosclerosis. The initiation and progression of atherosclerotic disease has been attributed to deficient vascular repair that results from obsolescence of bone marrow–derived EPCs. Reduced vascular progenitor cell content in aging bone marrow may cause the disequilibrium between reparative endothelial cells and inflammatory leukocytes, tipping the balance of injurious over reparative potentials.5 Low levels of circulating progenitor cells have been noted in high-risk CV patients and are considered to be the result of a combination of factors. CV risk factors can direct the function and life span of EPCs by modulating levels of oxidative stress, nitric oxide activity, or other physiological processes. Since EPCs have a role in maintaining vascular homeostasis, the impaired mobilization, exhaustion, or depletion of these progenitor cells can contribute to the perpetuation of endothelial dysfunction, reduce atheroprotection, and reduce progression of CV disease and other diseases that are age-related.6 EPCs from high-risk subjects are both fewer in number and become senescent more rapidly than do EPCs from low-risk subjects.6 Thus, levels of EPCs in healthy individuals