Kofron Celinda M, Mende Ulrike
Cardiovascular Research Center, Cardiovascular Institute, Rhode Island Hospital and Alpert Medical School of Brown University, Providence, RI, USA.
J Physiol. 2017 Jun 15;595(12):3891-3905. doi: 10.1113/JP273100. Epub 2017 Feb 27.
The heart is a complex pluricellular organ composed of cardiomyocytes and non-myocytes including fibroblasts, endothelial cells and immune cells. Myocytes are responsible for electrical conduction and contractile force generation, while the other cell types are responsible for matrix deposition, vascularization, and injury response. Myocytes and non-myocytes are known to communicate and exert mutual regulatory effects. In concert, they determine the structural, electrical and mechanical characteristics in the healthy and remodelled myocardium. Dynamic crosstalk between myocytes and non-myocytes plays a crucial role in stress/injury-induced hypertrophy and fibrosis development that can ultimately lead to heart failure and arrhythmias. Investigations of heterocellular communication in the myocardium are hampered by the intricate interspersion of the different cell types and the complexity of the tissue architecture. In vitro models have facilitated investigations of cardiac cells in a direct and controllable manner and have provided important functional and mechanistic insights. However, these cultures often lack regulatory input from the other cell types as well as additional topographical, electrical, mechanical and biochemical cues from the cardiac microenvironment that all contribute to modulating cell differentiation, maturation, alignment, function and survival. Advancements in the development of more complex pluricellular physiological platforms that incorporate diverse cues from the myocardial microenvironment are expected to lead to more physiologically relevant cardiac tissue-like in vitro models for mechanistic biological research, disease modelling, therapeutic target identification, drug testing and regeneration.
心脏是一个复杂的多细胞器官，由心肌细胞和非心肌细胞组成，非心肌细胞包括成纤维细胞、内皮细胞和免疫细胞。心肌细胞负责电传导和产生收缩力，而其他细胞类型则负责基质沉积、血管生成和损伤反应。已知心肌细胞和非心肌细胞会相互交流并发挥相互调节作用。它们共同决定了健康心肌和重塑心肌的结构、电学和力学特性。心肌细胞和非心肌细胞之间的动态相互作用在应激/损伤诱导的肥大和纤维化发展中起关键作用，最终可能导致心力衰竭和心律失常。心肌中不同细胞类型的复杂交织以及组织结构的复杂性阻碍了对异细胞间通讯的研究。体外模型以直接且可控的方式促进了对心脏细胞的研究，并提供了重要的功能和机制见解。然而，这些培养物通常缺乏其他细胞类型的调节输入，以及来自心脏微环境的额外地形、电学、力学和生化信号，而这些信号都有助于调节细胞分化、成熟、排列、功能和存活。开发更复杂的多细胞生理平台取得了进展，该平台整合了来自心肌微环境的各种信号，有望产生更具生理相关性的类似心脏组织的体外模型，用于机制生物学研究、疾病建模、治疗靶点识别、药物测试和再生。
