Intramyocardial Stem Cell Injection in Patients With Ischemic Cardiomyopathy: Functional Recovery and Reverse Remodeling

• Published in: Circulation research Vol. 108; no. 7; pp. 792 - 796
• Main Authors: Williams, Adam R, Trachtenberg, Barry, Velazquez, Darcy L, McNiece, Ian, Altman, Peter, Rouy, Didier, Mendizabal, Adam M, Pattany, Pradip M, Lopera, Gustavo A, Fishman, Joel, Zambrano, Juan P, Heldman, Alan W, Hare, Joshua M
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Heart Association, Inc 01.04.2011; Lippincott Williams & Wilkins
• Subjects: Adult; Aged; Biological and medical sciences; Cardiology. Vascular system; Fundamental and applied biological sciences. Psychology; Heart; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Humans; Injections; Magnetic Resonance Imaging; Male; Medical sciences; Mesenchymal Stem Cell Transplantation - adverse effects; Mesenchymal Stem Cell Transplantation - methods; Middle Aged; Myocardial Contraction - physiology; Myocardial Infarction - complications; Myocarditis. Cardiomyopathies; Pilot Projects; Recovery of Function - physiology; Treatment Outcome; Ventricular Dysfunction, Left - etiology; Ventricular Dysfunction, Left - physiopathology; Ventricular Dysfunction, Left - surgery; Ventricular Remodeling - physiology; Vertebrates: cardiovascular system; Human; Heart failure; stem cells; Cardiomyopathy; Stem cell; Cardiovascular disease; reverse remodeling; Myocardial disease; Vertebrata; Mammalia; Functional recovery; Ischemia; Heart disease; Bone marrow; Circulatory system; Intramyocardial
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/CIRCRESAHA.111.242610

RATIONALE:Transcatheter, intramyocardial injections of bone marrow–derived cell therapy produces reverse remodeling in large animal models of ischemic cardiomyopathy. OBJECTIVE:We used cardiac MRI (CMR) in patients with left ventricular (LV) dysfunction related to remote myocardial infarction (MI) to test the hypothesis that bone marrow progenitor cell injection causes functional recovery of scarred myocardium and reverse remodeling. METHODS AND RESULTS:Eight patients (aged 57.2±13.3 years) received transendocardial, intramyocardial injection of autologous bone marrow progenitor cells (mononuclear or mesenchymal stem cells) in LV scar and border zone. All patients tolerated the procedure with no serious adverse events. CMR at 1 year demonstrated a decrease in end diastolic volume (208.7±20.4 versus 167.4±7.32 mL; P=0.03), a trend toward decreased end systolic volume (142.4±16.5 versus 107.6±7.4 mL; P=0.06), decreased infarct size (P<0.05), and improved regional LV function by peak Eulerian circumferential strain in the treated infarct zone (−8.1±1.0 versus −11.4±1.3; P=0.04). Improvements in regional function were evident at 3 months, whereas the changes in chamber dimensions were not significant until 6 months. Improved regional function in the infarct zone strongly correlated with reduction of end diastolic volume (r=0.69, P=0.04) and end systolic volume (r=0.83, P=0.01). CONCLUSIONS:These data suggest that transcatheter, intramyocardial injections of autologous bone marrow progenitor cells improve regional contractility of a chronic myocardial scar, and these changes predict subsequent reverse remodeling. The findings support the potential clinical benefits of this new treatment strategy and ongoing randomized clinical trials.