Intracardiac transplantation of skeletal myoblasts yields two populations of striated cells in situ.

Abstract

Adult heart lacks stem cells and cannot effectively regenerate. In contrast, skeletal muscle is constantly undergoing repair. We proposed to transplant immature skeletal myoblasts into injured myocardium. Approximately 7x10(6) soleus skeletal myoblasts were expanded in vitro from adult New Zealand White rabbits (n = 23) whose posterior left ventricle was cryoinjured to create a transmural lesion. Autologous myoblasts (n = 18) or saline (n = 5) was transplanted into the central cryolesion at the time of injury (n = 6) or 1 week later (n = 12). Hearts were harvested 2 weeks after injection. Myoblast transfer did not incur further morbidity. After cryolesion, grossly, a 1.6-cm epicardial hemorrhagic lesion could be seen. Histologically, the transmural lesion contained inflammatory cells and active scarring but no viable cardiomyocytes. Electron microscopy demonstrated a predominance of collagen and fibroblasts. Nine hearts contained multinucleated cells within the cryolesion that covered approximately 75% of the central cryolesion in 17% of animals. Immunohistochemical analysis confirmed their skeletal muscle origin. At the periphery of the lesion, isolated clusters of nonskeletal muscle cells could be visualized (n = 12) that resembled immature cardiocytes. Autologous skeletal myoblasts can regenerate viable striated tissue within damaged myocardium. Myoblast transfer warrants further investigation as a new method for improving myocardial performance within infarcted myocardium.