Autologous Skeletal Myoblasts for Myocardial Regeneration TOMASZ SIMINIAK, M.D., Ph.D., F.E.S.C., F.A.C.C., 1 PIOTR KALMUCKI, M.D., 1 and MACIEJ KURPISZ, M.D., Ph.D. 2 From the 1 Department of Cardiology, University School of Medical Sciences, District Hospital, Pozna´ n; 2 Institute of Human Genetics, Polish Academy of Sciences, Pozna´ n, Poland We overview the current knowledge about the use of skeletal myoblasts in regeneration of infarcted myocardium. Myoblasts are attractive candidates for cell source for cardiomyoplasty in chronic postmyocardial injury as indi- cated by experimental and initial clinical experience. We also review the recent developments in skeletal myoblasts transplantaion techniques with special attention to percutaneous transvenous approach to deliver therapeutic agents into myocardium from the lumen of coronary veins under intravascular guidance. (J Interven Cardiol 2004;17:357–365) Introduction Urgent reperfusion, by mechanical or pharmaco- logical methods and restoration of blood flow in the occluded artery lead to the reduction of myocardial size, subsequent reduction in mortality rates, and im- proved clinical outcome in patients with acute myocar- dial infarction (AMI). Therefore, the minimization of infarct size is the main aim in the management of AMI patients. Unfortunately, in certain group of patients, it is difficult to achieve in clinical practice. Cardiac tis- sue becomes necrotic relatively quickly and 3 hours after total occlusion infarct reaches almost 80% of its size. 1 Despite recent therapeutic advances, MI and sub- sequent congestive heart failure continues to be a major health problem. Routine revascularization procedures enable recovery of contractile function only in the areas of hibernating myocardium, having a certain amount of viable, reversibly injured myocytes. Fibrotic scar leads to decreased systolic function, left ventricular remod- eling, aneurysm formation, and progression of conges- tive heart failure. Ideally, nonviable, fibrotic scar that is unable to con- tract should be replaced by new, functionally effective Address for reprints: Tomasz Siminiak, M.D., Ph.D., F.E.S.C., F.A.C.C., Department of Cardiology, University School of Medical Sciences, District Hospital, ul. Juraszow 7/19, PL 60-479 Pozna´ n, Poland. Fax: +48-61-8212319, e-mail: tomasz.siminiak@usoms.poznan.pl cardiac tissue. Cardiac transplantation may be an op- tion in selected patients, but due to organ shortage, its practical use is limited. This resulted in the develop- ment of alternative therapeutic method based on the restoration of the total amount of contractile cells, i.e., myocardial regeneration. The transformation of non- myogenic in-scar fibroblasts into contracting cells or attempts to induce cardiomyocytes to reentry the cellu- lar cycle are not clinically applicable for close future. 2 At the moment, the only practically realistic therapy is exogenous cell supply to repopulate infarcted areas. So far, with the aim to replace necrotic tissue, in ani- mal models and recently in humans, many different cell types have been transplanted into myocardium. Among them autologous skeletal myoblasts are one of the most encouraging cell source for cardiac repair because of their biological properties and lack of ethical and im- munological problems. Numerous studies have explored different delivery techniques. As skeletal myoblasts do not extravasate their potential application in myocardial regeneration requires direct cell injection into the area of damaged myocardium. Therefore surgical approach (open-chest surgery) and several catheter-based methods had been proposed. In this article, we focus on potential value and prob- lems of autologous skeletal myoblasts transplantation. We also review possible techniques that could be uti- lized in cell implantation with a special attention to Vol. 17, No. 6, 2004 Journal of Interventional Cardiology 357