Congestive heart failure remains a major cause of morbidity and mortality. While left ventricular assist devices have shown promise as bridges to transplant and even may provide long-term benefits, they may develop mechanical difficulty, thromboembolism, infection, and require anticoagulation. Recently we have shown that we can inject neonatal or fetal cardiac myocytes into the collagenous wall of a myocardial infarct scar in the rat model. These cells grow, differentiate, develop sarcomeres, survive for at least 6 months, and importantly contribute to improved left ventricular ejection fraction and regional wall motion. In the current application we propose to assess the utility of transplanting neonatal or fetal cardiac cells directly into the aorta of rodents. The concept is to build a biologic ventricular assist device or an auxiliary heart. A circumferential cuff of myocardial cells approximately 3 mm in length and about 2 mm in thickness will be made upon the outer wall of the abdominal aorta above the take off of the renal arteries of the rat. Once these cells mature into an adult phenotype they will be paced to contract at the time of the host's diastole to simulate an intraaortic balloon counterpulsation device. Diastolic contraction of the lower aorta should drive blood forward into the lower half of the body, reduce afterload, and improve diastolic coronary flow by improving coronary artery driving pressure. A rat model of myocardial infarction will be used to assess the ability of this biologic pump approach to improve hemodynamics and left ventricular function via an afterload-reducing mechanism. Our pilot studies show that it is feasible to inject cells into the outer aortic wall. Improvement in hemodynamics and blood flow will be determined utilizing rodent LV angiography and catheterization as well as radioactive microspheres. Identification and characterization of transplants will be carried out with PCR analysis of the Y chromosome (male cells into female host), detailed histologic analysis and immunostaining for muscle cell markers.
| Wold, Loren E; Dai, Wangde; Dow, Joan S et al. (2007) Stem cell therapy in the heart and vasculature. Methods Mol Med 139:355-65 |
| Dai, Wangde; Hale, Sharon L; Kloner, Robert A (2007) Development of a spontaneously beating vein by cardiomyocyte transplantation in the wall of the inferior vena cava in a rat: a pilot study. J Vasc Surg 45:817-20 |
| Dai, Wangde; Hale, Sharon L; Kloner, Robert A (2006) Cardiac cells implanted within the outer aortic wall of rats generate measurable contractile force. Regen Med 1:119-24 |
| Dai, Wangde; Hale, Sharon L; Kloner, Robert A (2004) Implantation of immature neonatal cardiac cells into the wall of the aorta in rats: a novel model for studying morphological and functional development of heart cells in an extracardiac environment. Circulation 110:324-9 |
