Autologous Cell Transplantation for the Treatment of Damaged Myocardium Marc S. Penn, Gary S. Francis, Stephen G. Ellis, James B. Young, Patrick M. McCarthy, and Eric J. Topol Autologous cell transplantation for the treatment of damaged myocardium after myocardial infarction is becoming an increasingly promising strategy. This form of treatment can be divided into 2 treat- ment strategies: The first uses differentiated cell types to replace the scarred tissue with living cells, while the second strategy uses stem cells in an attempt to regenerate myocardium. Over the past decade, multiple cell types have been used in an- imal studies, and clinical trials to determine the safety of injecting and engrafting skeletal myo- blasts into damaged myocardium are presently be- ing conducted. Animals studies focused on using stem cells to regenerate damaged myocardium have shown a naturally occurring reparative pro- cess that consists of up-regulation of progenitor cell release from the bone marrow after myocardial infarction, homing of these cells to the injured tis- sue, and differentiation of these progenitor cells into vascular cells and cardiac myocytes within the infarcted tissue. Unfortunately, this process occurs with great infrequency. Strategies to regenerate myocardium with stem cells either extract stem cells from the bone marrow and inject these cells into the damaged area or they attempt to increase the efficiency of the natural reparative process by increasing the mobilization of bone marrow–de- rived stem cells after myocardial infarction. This review summarizes the field of cell transplantation over the past decade, discusses areas of contro- versy, and proposes an outline of advancements that need to be made in both the clinical and scientific arenas for autologous cell transplantation to fully reach its clinical potential. Copyright 2002, Elsevier Science (USA). All rights reserved. R ecent clinical trials of acute myocardial in- farction testing enhanced reperfusion strate- gies have failed to demonstrate a significant im- provement in mortality. These recent studies also demonstrated that no significant progress has been made on encouraging patients to present ear- lier with their symptoms since the time to presen- tation for patients enrolled in clinical trials, nearly 3 hours after symptom onset, has not changed over the past decade. These observations demon- strate that need for the development of a new treatment paradigm for the treatment of patients with acute myocardial infarction and the conse- quences of myocardial necrosis. Strategies are needed to either (1) prevent myocardial cell loss during acute myocardial infarction, (2) optimize the pathological remodeling, or (3) regenerate myocardium after acute myocardial infarction, particularly since now over 10% of the American population over 65 years of age has congestive heart failure. The concept of transplanting autologous cells successfully into a damaged heart has received significant attention. Clinical trials are ongoing that examine the safety and efficacy of autologous skeletal myoblast transplantation in patients ini- tially as an adjunct to coronary artery bypass sur- gery. 1 Furthermore, case studies using autologous bone marrow transplantation after acute myocar- dial infarction are beginning to appear at national meetings describing experiences with bone mar- row cells injected into the myocardium or directly through the infarct-related epicardial artery. 2 From the Departments of Cardiovascular Medicine, Cell Biology, and Cardiothoracic Surgery, Cleveland Clinic Foundation, Cleveland, OH. Address reprint requests to Marc S. Penn, MD, PhD, Director, Experimental Animal Laboratory Departments of Cardiovascular Medicine and Cell Biology, 9500 Euclid Avenue, NC10, Cleveland, OH 44195. Copyright 2002, Elsevier Science (USA). All rights reserved. 0033-0620/02/4501-0001$35.00/ 22/1/123466 doi:10.1053/pcad.2002.123466 21 Progress in Cardiovascular Diseases, Vol. 45, No. 1, (July/August) 2002: pp 21-32