Cell Delivery: Intramyocardial Injections or Epicardial Deposition? A Head-to-Head Comparison

Background Multiple needle-based injections of cells in the myocardium are associated with a low engraftment rate, which may limit the benefits of the procedure. This study used skeletal myoblasts to perform a head-to-head comparison of conventional injections with epicardial deposition of scaffold-embedded cells. Methods Four weeks after ligation-induced myocardial infarction, 40 rats were randomly allocated to receive intramyocardial injections of 5 million human skeletal myoblasts or control medium or to have the infarcted area covered with either a bilayer myoblast cell sheet prepared from a fibrin-coated culture plate or a myoblast-seeded collagen sponge (Gelfoam; Pharmacia & Upjohn, Kalamazoo, MI). End points, assessed after 1 month, included left ventricular function blindly measured by echocardiography, quantification of cell engraftment by quantitative real-time polymerase chain reaction and immunostaining, histologic assessment of fibrosis and angiogenesis, and tissue levels of host-specific angiogenic and antifibrotic cytokines. Results Compared with control medium- or myoblast-injected hearts, those receiving the two cell constructs demonstrated the highest recoveries of left ventricular function ( p = 0.004 versus controls). Both myoblast cell sheets and myoblast-seeded Gelfoam sponges also resulted in significantly greater angiogenesis compared with controls. The Gelfoam group was associated with the best outcome with regard to the number of engrafted donor cells ( p = 0.03 versus myoblasts) and the reduction of fibrosis ( p = 0.02 and p = 0.04 versus the control and myoblast groups, respectively). Conclusions Compared with injections, delivery of myoblasts in a construct overlaying the infarcted area is associated with better graft functionality, possibly because of maintenance of improved cell patterning. The cell-seeded Gelfoam construct was found to feature a user-friendly, reproducible, and atraumatic technique.