Department of Cardiology, Southern Arizona VA HealthCare System, Tucson, Arizona 85723, USA.
Tissue Eng Part A. 2010 Oct;16(10):3065-73. doi: 10.1089/ten.TEA.2009.0589.
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.
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.
Implanting the 3DFC increases (p<0.05) myocardial blood flow twofold, microvessel formation (0.02±0.01 vs. 0.07±0.03 vessels/μm2), 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.
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.
本研究在慢性心力衰竭模型中检查了一种可行的可生物降解的三维成纤维细胞构建体(3DFC)。培养在维可牢尼龙网上的活成纤维细胞分泌刺激血管生成的生长因子。
我们结扎雄性 Sprague-Dawley 大鼠的左冠状动脉,在心肌梗死后 3 周植入 3DFC,并在 3 周后即心肌梗死后 6 周获得终点数据。
植入 3DFC 使心肌血流增加两倍(p<0.05),微血管形成(0.02±0.01 对 0.07±0.03 血管/μm2),心室壁厚度增加(0.53±0.02 至 1.02±0.17mm)。3DFC 将被动压力-容积环移向压力轴,但不改变左心室(LV)射血分数、收缩位移、LV 舒张末期压/尺寸或 LV 腔面积。3DFC 刺激选定的细胞因子激活,减少促炎级联反应,并增加体外应变 3DFC 刺激的总蛋白含量。
3DFC 作为细胞输送装置,为驻留细胞的存活和整合到心脏提供基质支持。3DFC 的嵌入式成纤维细胞释放出一种复杂的心脏活性细胞因子混合物,促进微血管密度和前壁血流增加,但不改善射血分数或改变 LV 重塑。