Novel regenerative therapy using cell-sheet covered with omentum flap delivers a huge number of cells in a porcine myocardial infarction model

ObjectiveA key challenge to applying cell transplantation to treat severely damaged myocardium is in delivering large numbers of cells with minimum cell loss. We developed a new implantation method using skeletal myoblast (SMB) sheets, wrapped with an omentum flap as a blood supply to deliver huge numbers of SMBs to the damaged heart. We examined whether this method could be used to deliver a large amount of cells to deteriorated porcine myocardium.MethodsCell sheets were obtained by culturing mini-pig autologous SMB cells on temperature-responsive culture dishes. Myocardial infarction was induced by placing an ameroid constrictor around the left anterior descending artery. The mini-pigs were divided into 4 treatment groups (n = 6 in each): cell sheets with omentum, cell sheets only, omentum only, and sham operation. Each animal implant consisted of 30 cell sheets (1.5 × 107 cells per sheet). Six 5-layer constructs were each placed on a different area, immediately adjacent to but not overlapping one another, to cover the infarct and border regions.ResultsThe new regenerative cell delivery system using SMB sheets covered and wrapped with omentum resulted in (1) a significantly reduced infarct size causing, at least in part, a thin scar with thick well-vascularized cardiac tissue; (2) increased angiogenesis, as determined by a significantly higher vascular density; and (3) improved cardiac function, as determined by echocardiography, compared with the conventional method (SMB sheet implantation).ConclusionsThis cell delivery system shows potential for repairing the severely failed heart.