Viable fibroblast matrix patch induces angiogenesis and increases myocardial blood flow in heart failure after myocardial infarction.

摘要

BACKGROUND: This study examines a viable biodegradable three-dimensional fibroblast construct (3DFC) in a model of chronic heart failure. The viable fibroblasts, cultured on a vicryl mesh, secrete growth factors that stimulate angiogenesis. METHODS: We ligated the left coronary artery of male Sprague-Dawley rats, implanted the 3DFC 3 weeks after myocardial infarction and obtained end point data 3 weeks later, that is, 6 weeks after myocardial infarction. RESULTS: Implanting the 3DFC increases (p<0.05) myocardial blood flow twofold, microvessel formation (0.02+/-0.01 vs. 0.07+/-0.03 vessels/mum2), and ventricular wall thickness (0.53+/-0.02 to 1.02+/-0.17mm). The 3DFC shifts the passive pressure volume loop toward the pressure axis but does not alter left ventricular (LV) ejection fraction, systolic displacement, LV end-diastolic pressure/dimension, or LV cavity area. The 3DFC stimulates selected cytokine activation with a decrease in the proinflammatory cascade and increased total protein content stimulated by strained 3DFC in vitro. CONCLUSION: The 3DFC functions as a cell delivery device providing matrix support for resident cell survival and integration into the heart. The imbedded fibroblasts of the 3DFC release a complex blend of cardioactive cytokines promoting increases in microvessel density and anterior wall blood flow but does not improve ejection fraction or alter LV remodeling.