Department of Materials Engineering, Monash University, Clayton, VIC 3800, Australia.
Biomaterials. 2010 May;31(14):3885-93. doi: 10.1016/j.biomaterials.2010.01.108. Epub 2010 Feb 11.
We hypothesize that a combinatorial approach of ventricle constraint and stem cell therapy would offer a greater benefit for the treatment of heart failure than either strategy alone. A heart patch would serve two therapeutic purposes: biomechanical support and cell delivery. In this study, we describe a hybrid heart patch engineered from a synthetic elastomer, poly(glycerol sebacate) (PGS), supplemented with cardiomyocytes differentiated from human embryonic stem cells (hESCs). In line with two therapeutically relevant considerations, i.e. biocompatibility and cell delivery efficiency, the PGS was (a) pre-conditioned in culture medium for 6 days, and (b) prepared without gelatin coatings to facilitate detachment and delivery of cardiomyocytes following patch implantation. Following pre-conditioning under physiological conditions, the PGS patch material without gelatin coating was found to satisfactorily support cardiomyocyte viability and attachment, with active cell beating for periods of longer than 3 months until interrupted. Dynamic culture studies revealed that cells detached more efficiently from the uncoated surface of PGS than from gelatin-coated PGS. No significant differences were detected between the beating rates of human embryonic stem cell-derived cardiomyocytes on tissue culture plate and the pre-conditioned and gelatin-uncoated PGS. PGS patches sutured over the left ventricle of rats in vivo remained intact over a 2 week period without any deleterious effects on ventricular function. We conclude that PGS is a suitable biomaterial for stem cell-based regeneration strategies to restore cardiomyocyte function, and the hybrid heart patch engineered under optimal conditions would be a promising support device for the cardiac repair.
我们假设，心室约束和干细胞治疗的组合方法将比单一策略为心力衰竭的治疗带来更大的益处。心脏补片将具有两种治疗目的：生物力学支持和细胞递送。在这项研究中，我们描述了一种由合成弹性体聚（甘油 - 癸二酸酯）（PGS）制成的混合心脏补片，补充了从人类胚胎干细胞（hESC）分化而来的心肌细胞。符合两种治疗相关的考虑因素，即生物相容性和细胞递送效率，PGS 被（a）在培养基中预处理 6 天，和（b）制备而没有明胶涂层，以方便补片植入后心肌细胞的分离和递送。在生理条件下进行预处理后，发现没有明胶涂层的 PGS 补片材料能够令人满意地支持心肌细胞的活力和附着，细胞搏动活跃时间超过 3 个月，直到中断。动态培养研究表明，细胞从未涂层的 PGS 表面比从明胶涂层的 PGS 表面更有效地分离。在组织培养板上和预处理的、无明胶涂层的 PGS 上，人胚胎干细胞来源的心肌细胞的搏动率没有显著差异。体内缝合在大鼠左心室上的 PGS 补片在 2 周内保持完整，对心室功能没有任何不良影响。我们得出结论，PGS 是一种适合基于干细胞的再生策略的生物材料，可恢复心肌细胞功能，而在最佳条件下设计的混合心脏补片将是一种有前途的心脏修复支持设备。
