Scaffold-based three-dimensional human fibroblast culture provides a structural matrix that supports angiogenesis in infarcted heart tissue

Background-We have developed techniques to implant angiogenic patches onto the epicardium over regions of infarcted cardiac tissue to stimulate revasc ularization of the damaged tissue. These experiments used a scaffold-based 3D human dermal fibroblast culture (3DFC) as an epicardial patch. The 3DFC contains viable cells that secrete angiogenic growth factors and has previo usly been shown to stimulate angiogenic activity. The hypothesis tested was that a viable 3DFC cardiac patch would stimulate an angiogenic response wi thin an area of infarcted cardiac tissue. Methods and Results-A coronary occlusion of a branch of the left anterior d escending coronary artery was performed by thermal ligation in severe combi ned immunodeficient mice. 3DFCs with or without viable cells were sized to the damaged area, implanted in replicate mice onto the epicardium at the si te of tissue injury, and compared with animals that received infarct surger y but no implant. Fourteen and 30 days after surgery, hearts were exposed a nd photographed, and tissue samples were prepared for histology and cytoche mistry. Fourteen and 30 days after surgery, the damaged myocardium receivin g viable 3DFC exhibited a significantly greater angiogenic response (includ ing arterioles, venules, and capillaries) than nonviable and untreated cont rol groups. Conclusions-In this animal model, viable 3DFC stimulates angiogenesis withi n a region of cardiac infarction and can augment a repair response in damag ed tissue. Therefore, a potential use for 3DFC is the repair of myocardial tissue damaged by infarction.