chapter  11
Transplantation of Genetically Engineered Cardiac Fibroblasts Producing Recombinant Human Erythropoietin to Repair the Infarcted Myocardium
Pages 20

Background Erythropoietin (EPO), a hematopoietic cytokine, has been shown to possess cardioprotective characteristics that can minimize ischemic injury and improve myocardial viability and function [1]. Systemic administration of recombinant human EPO (rhEPO) before or after myocardial ischemia reduces infarct size and improves cardiac function [2,3]. e benecial eects of EPO are mediated by apoptosis inhibition, driven by Akt/phosphoinositide3-kinase signaling [4,5], and neovascularization by stimulation of endothelial progenitor cells [6,7]. However, systemic administration of EPO to patients with coronary artery disease could lead to adverse eects, such as high viscocity, impaired tissue perfusion, high blood pressure and an increased incidence of thrombosis [8,9]. Hematocrit elevation has been linked to excess mortality in patients with ischemic heart disease [10,11]. Over-expression of rhEPO in transgenic mice resulted in cardiac dysfunction and reduced life span [12,13]. Overall, the potential adverse eects

associated with systemic EPO administration suggest that alternative approaches are needed.