Cardiology and Medicine, Southern Arizona VA Health Care System; Sarver Heart Center; Department of Physiology.
Cardiology and Medicine, Southern Arizona VA Health Care System; Sarver Heart Center.
J Heart Lung Transplant. 2014 Apr;33(4):438-45. doi: 10.1016/j.healun.2013.12.004. Epub 2013 Dec 17.
Varying strategies are currently being evaluated to develop tissue-engineered constructs for the treatment of ischemic heart disease. This study examines an angiogenic and biodegradable cardiac construct seeded with neonatal cardiomyocytes for the treatment of chronic heart failure (CHF).
We evaluated a neonatal cardiomyocyte (NCM)-seeded 3-dimensional fibroblast construct (3DFC) in vitro for the presence of functional gap junctions and the potential of the NCM-3DFC to restore left ventricular (LV) function in an in vivo rat model of CHF at 3 weeks after permanent left coronary artery ligation.
The NCM-3DFC demonstrated extensive cell-to-cell connectivity after dye injection. At 5 days in culture, the patch contracted spontaneously in a rhythmic and directional fashion at 43 ± 3 beats/min, with a mean displacement of 1.3 ± 0.3 mm and contraction velocity of 0.8 ± 0.2 mm/sec. The seeded patch could be electrically paced at nearly physiologic rates (270 ± 30 beats/min) while maintaining coordinated, directional contractions. Three weeks after implantation, the NCM-3DFC improved LV function by increasing (p < 0.05) ejection fraction 26%, cardiac index 33%, dP/dt(+) 25%, dP/dt(-) 23%, and peak developed pressure 30%, while decreasing (p < 0.05) LV end diastolic pressure 38% and the time constant of relaxation (Tau) 16%. At 18 weeks after implantation, the NCM-3DFC improved LV function by increasing (p < 0.05) ejection fraction 54%, mean arterial pressure 20%, dP/dt(+) 16%, dP/dt(-) 34%, and peak developed pressure 39%.
This study demonstrates that a multicellular, electromechanically organized cardiomyocyte scaffold, constructed in vitro by seeding NCM onto 3DFC, can improve LV function long-term when implanted in rats with CHF.
目前正在评估各种策略，以开发用于治疗缺血性心脏病的组织工程构建体。本研究检查了一种血管生成和可生物降解的心脏构建体，该构建体接种了新生儿心肌细胞，用于治疗慢性心力衰竭 (CHF)。
我们评估了体外接种有新生儿心肌细胞 (NCM) 的 3 维成纤维细胞构建体 (3DFC) 是否存在功能间隙连接，以及 NCM-3DFC 在永久性左冠状动脉结扎后 3 周的 CHF 大鼠模型中恢复左心室 (LV) 功能的潜力。
NCM-3DFC 在染料注射后表现出广泛的细胞间连接。在培养的第 5 天，贴片以 43 ± 3 次/分钟的节律和定向方式自发收缩，平均位移为 1.3 ± 0.3 毫米，收缩速度为 0.8 ± 0.2 毫米/秒。接种的贴片可以以接近生理的速率（270 ± 30 次/分钟）起搏，同时保持协调的定向收缩。植入后 3 周，NCM-3DFC 通过增加（p < 0.05）射血分数 26%、心指数 33%、dP/dt(+) 25%、dP/dt(-) 23%和峰值发展压力 30%，同时降低（p < 0.05）LV 舒张末期压力 38%和弛豫时间常数 (Tau) 16%，改善 LV 功能。植入后 18 周，NCM-3DFC 通过增加（p < 0.05）射血分数 54%、平均动脉压 20%、dP/dt(+) 16%、dP/dt(-) 34%和峰值发展压力 39%，改善 LV 功能。
本研究表明，通过将 NCM 接种到 3DFC 上体外构建的多细胞、机电组织化的心肌细胞支架，在 CHF 大鼠中植入后可长期改善 LV 功能。
