Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Tokyo 162-8666, Japan.
Biochem Biophys Res Commun. 2012 Aug 24;425(2):321-7. doi: 10.1016/j.bbrc.2012.07.089. Epub 2012 Jul 25.
Although we previously reported the development of cell-dense thickened cardiac tissue by repeated transplantation-based vascularization of neonatal rat cardiac cell sheets, the cell sources for human cardiac cells sheets and their functions have not been fully elucidated. In this study, we developed a bioreactor to expand and induce cardiac differentiation of human induced pluripotent stem cells (hiPSCs). Bioreactor culture for 14 days produced around 8×10(7) cells/100 ml vessel and about 80% of cells were positive for cardiac troponin T. After cardiac differentiation, cardiomyocytes were cultured on temperature-responsive culture dishes and showed spontaneous and synchronous beating, even after cell sheets were detached from culture dishes. Furthermore, extracellular action potential propagation was observed between cell sheets when two cardiac cell sheets were partially overlaid. These findings suggest that cardiac cell sheets formed by hiPSC-derived cardiomyocytes might have sufficient properties for the creation of thickened cardiac tissue.
虽然我们之前报道了通过重复基于细胞片的血管化来构建细胞密集的增厚心脏组织,但用于人心肌细胞片的细胞来源及其功能尚未完全阐明。在这项研究中,我们开发了一种生物反应器来扩增和诱导人诱导多能干细胞(hiPSC)的心脏分化。生物反应器培养 14 天可产生约 8×10(7)个细胞/100ml 容器,约 80%的细胞对心肌肌钙蛋白 T 呈阳性。心脏分化后,心肌细胞在温度响应培养皿上培养,即使在细胞片从培养皿上脱落之后,仍可自发且同步搏动。此外,当两个心肌细胞片部分重叠时,可观察到细胞片之间的细胞外动作电位传播。这些发现表明,由 hiPSC 衍生的心肌细胞形成的心肌细胞片可能具有构建增厚心脏组织的足够特性。