Disease Biophysics Group, School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA ; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA ; Wyss Institute of Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
Stem Cell Reports. 2013 Nov 7;1(5):387-96. doi: 10.1016/j.stemcr.2013.10.004. eCollection 2013.
Stem cell-derived cardiomyocytes represent unique tools for cell- and tissue-based regenerative therapies, drug discovery and safety, and studies of fundamental heart-failure mechanisms. However, the degree to which stem cell-derived cardiomyocytes compare to mature cardiomyocytes is often debated. We reasoned that physiological metrics of engineered cardiac tissues offer a means of comparison. We built laminar myocardium engineered from cardiomyocytes that were differentiated from mouse embryonic stem cell-derived cardiac progenitors or harvested directly from neonatal mouse ventricles, and compared their anatomy and physiology in vitro. Tissues assembled from progenitor-derived myocytes and neonate myocytes demonstrated similar cytoskeletal architectures but different gap junction organization and electromechanical properties. Progenitor-derived myocardium had significantly less contractile stress and slower longitudinal conduction velocity than neonate-derived myocardium, indicating that the developmental state of the cardiomyocytes affects the electromechanical function of the resultant engineered tissue. These data suggest a need to establish performance metrics for future stem cell applications.
干细胞衍生的心肌细胞是细胞和组织再生治疗、药物发现和安全性以及心力衰竭机制基础研究的独特工具。然而，干细胞衍生的心肌细胞与成熟心肌细胞的相似程度常常存在争议。我们推断，工程化心脏组织的生理指标提供了一种比较方法。我们构建了由从鼠胚胎干细胞衍生的心脏祖细胞分化而来的心肌细胞或直接从新生鼠心室中收获的心肌细胞分化而来的心肌细胞组成的层状心肌，并在体外比较了它们的解剖结构和生理学特性。由祖细胞衍生的心肌细胞和新生心肌细胞组装的组织具有相似的细胞骨架结构，但间隙连接组织和机电特性不同。与由新生鼠衍生的心肌细胞相比，祖细胞衍生的心肌细胞的收缩力显著降低，纵向传导速度较慢，表明心肌细胞的发育状态影响工程化组织的机电功能。这些数据表明，需要为未来的干细胞应用建立性能指标。
