Novel Stem Cell Therapy for Acute Myocardial Infarction in Diabetes Mellitus

ABSTRACT Novel Stem Cell Therapy for Acute Myocardial Infarction in Diabetes Mellitus Cardiovascular disease CVD is the leading cause of mortality and morbidity worldwide leading to over million deaths per year Over heart attacks occur in the U S each year which cause about deaths After acute myocardial infarction AMI ischemic tissues undergo cell death from necrosis and apoptosis followed by inflammation and a process of granulation leading to scar tissue formation Due to the poor regenerative ability of cardiomyocytes improved therapies are sorely needed to both protect and restore ischemic tissues immediately post AMI Patients with type diabetes mellitus T DM have a higher incidence of CVD and worse prognosis than those without diabetes Williams approximately two thirds of diabetic associated deaths are due to heart disease or stroke Fox Dailey Intl Diabetes Federation and those with AMI have higher rates of re occlusion and both day and year mortality Williams Moreover women diagnosed with diabetes after age have a significantly greater risk of CVD mortality and hospitalization than men Roche Overwhelming evidence supports a direct link between diabetic vascular complications and endothelial dysfunction Jarajapu The inability to repair damaged vasculature is due in large part not only to a reduction in the number of circulating endothelial progenitor cells EPC but by their altered cytokine profiles and reduced migratory and proliferative potentials Consequently in multiple animal models of ocular vascular damage EPC obtained from normal individuals were able to attach to and assimilate into the damaged vasculature while those from age and sex matched diabetic patients lacked any regenerative ability Caballero For T DM patients with AMI deficiencies in their endogenous EPC make them minimally responsive to pharmacological approaches Jarajapu and unsuitable candidates for current approaches to autologous cell therapy The goal of this project is to develop a novel stem cell delivery method that addresses the regenerative deficiencies of stem progenitor cells of all patients after AMI in particular higher risk patients with T DM We will demonstrate the efficiency of this technology with cord blood and peripheral blood derived stem cells the former demonstrate high migratory and regenerative properties while those from peripheral blood show much lower migrating potential and should benefit more significantly from our approach Aiuti Success in enabling poorly migrating stem cells to revascularize and protect ischemic myocardium will warrant a Ph application Ph work will focus on obtaining the preclinical data necessary for submission of an IND to perform PhI II trials in patients with AMI Patients will be randomized to receive conventional therapy vs conventional therapy plus BiAb armed stem cells and would include both diabetic and non diabetic patients NARRATIVE Diabetes mellitus is a worldwide health problem and a major risk factor for mortality and hospitalization due to cardiovascular disease We are developing a novel stem cell therapy to rescue the therapeutic activity of dysfunctional circulating stem cells involved in repairing damaged myocardial tissue after acute myocardial infarction