Unveiling the molecular crosstalk in a human induced pluripotent stem cell-derived cardiac model
Unveiling the molecular crosstalk in a human induced pluripotent stem cell-derived cardiac model
复制标题
DOI：
10.1002/bit.26929
复制
发表时间：
2019-05-01
影响因子：
3.8
通讯作者：
Alves, Paula M.
中科院分区：
文献类型：
--
作者：
Abecasis, Bernardo;Gomes-Alves, Patricia;Alves, Paula M.
更好地模拟人类心脏组织的体外细胞模型对于药物开发和心脏毒性测试至关重要，而且也是在细胞和分子水平上了解心脏疾病相关机制的工具。此外，实现分析工具，使不同细胞类型之间的串扰的分子机制的描述和全面的理解也是相关的。在这项工作中，我们实施了一个人心脏组织样的体外模型，来自人类诱导的多能干细胞（hiPSC），并评估了人类心脏的两个最具代表性的细胞群：心肌细胞（hiPSC-CM）和内皮细胞（hiPSC-EC）之间的细胞-细胞通信的相关性。我们观察到异型细胞通讯促进：（a）hiPSC-CM的结构成熟和（B）几种细胞外基质成分（如胶原蛋白和纤连蛋白）的沉积。总的来说，我们研究中使用的分析技术工具箱不仅使我们能够验证先前文献中关于hiPSC-EC存在对hiPSC-CM成熟的重要性的报道，而且还为体外共培养时这两种细胞类型之间的通信所涉及的分子机制带来了新的见解。
In vitro cell-based models that better mimic the human heart tissue are of utmost importance for drug development and cardiotoxicity testing but also as tools to understand mechanisms related with heart disease at cellular and molecular level. Besides, the implementation of analytical tools that allow the depiction and comprehensive understanding of the molecular mechanisms of the crosstalk between the different cell types is also relevant. In this work, we implemented a human cardiac tissue-like in vitro model, derived from human-induced pluripotent stem cell (hiPSC), and evaluated the relevance of the cell-cell communication between the two of the most representative cell populations of the human heart: cardiomyocytes (hiPSC-CM) and endothelial cells (hiPSC-EC). We observed that heterotypic cell communication promotes: (a) structural maturation of hiPSC-CM and (b) deposition of several extracellular matrix components (such as collagens and fibronectin). Overall, the toolbox of analytical techniques used in our study not only enabled us to validate previous reports from the literature on the importance of the presence of hiPSC-EC on hiPSC-CM maturation, but also bring new insights on the molecular mechanisms involved in the communication between these two cell types when cocultured in vitro.