Cardiac Patch Constructed from Human Fibroblasts Attenuates Reduction in Cardiac Function after Acute Infarct

Abstract

The current experiments used a scaffold-based, three-dimensional, human dermal fibroblast culture (3DFC) as a cardiac patch to stimulate revascularization and preserve left ventricular (LV) function of the infarcted LV in severe combined immunodeficient (SCID) mice. The 3DFC contains viable cells that secrete angiogenic growth factors and has been previously shown to stimulate angiogenesis. The hypothesis tested was that a 3DFC cardiac patch would attenuate a reduction in LV function of infarcted hearts. Five groups of mice were studied, including normal SCID mice (n = 13), normal SCID mice with 3DFC (n = 6), infarcted SCID mice (n = 6), infarcted mice with nonviable 3DFC (n = 6), and infarcted SCID mice with 3DFC (n = 6). An occlusion of a branch of the left anterior descending (LAD) coronary artery was performed by thermal ligation, and 3DFC was sized to the damaged area and implanted onto the epicardium at the site of tissue injury. Fourteen days postsurgery, LV mechanics were characterized with the Millar conductance catheter system (CCS). The data demonstrated that 3DFC-treated infarcted myocardium had significantly higher ejection fractions (EFs) compared with infarct-only mice (58.9 ± 10.8 versus 31.0 ± 5.8%, respectively; p < 0.05). Preload recruitable stroke work (PRSW) parameters were significantly higher in 3DFC-treated mice compared with infarct-only mice (64.6 ± 11.9 versus 36.8 ± 6.4 mmHg, respectively; p < 0.05). These results show that the 3DFC as a cardiac patch functioned to attenuate further loss of LV function accompanying acute myocardial infarct and that this may be related in part to myocardial revascularization.