Division of Physiology, Department of Experimental and Clinical Medicine, Università degli Studi di Firenze, Florence, Italy.
Unità di Biologia Vascolare e Medicina Rigenerativa, Centro Cardiologico Monzino IRCCS, via Carlo Parea 4, Milan, Italy; Department of Electronics, Information and Biomedical Engineering, Politecnico di Milano, Milan, Italy.
J Mol Cell Cardiol. 2022 May;166:36-49. doi: 10.1016/j.yjmcc.2022.02.001. Epub 2022 Feb 6.
The quest for novel methods to mature human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) for cardiac regeneration, modelling and drug testing has emphasized a need to create microenvironments with physiological features. Many studies have reported on how cardiomyocytes sense substrate stiffness and adapt their morphological and functional properties. However, these observations have raised new biological questions and a shared vision to translate it into a tissue or organ context is still elusive. In this review, we will focus on the relevance of substrates mimicking cardiac extracellular matrix (cECM) rigidity for the understanding of the biomechanical crosstalk between the extracellular and intracellular environment. The ability to opportunely modulate these pathways could be a key to regulate in vitro hiPSC-CM maturation. Therefore, both hiPSC-CM models and substrate stiffness appear as intriguing tools for the investigation of cECM-cell interactions. More understanding of these mechanisms may provide novel insights on how cECM affects cardiac cell function in the context of genetic cardiomyopathies.
寻求将人类诱导多能干细胞衍生的心肌细胞（hiPSC-CMs）成熟用于心脏再生、建模和药物测试的新方法，强调了需要创建具有生理特征的微环境。许多研究报告了心肌细胞如何感知基质硬度并适应其形态和功能特性。然而，这些观察结果提出了新的生物学问题，将其转化为组织或器官背景的共同愿景仍然难以捉摸。在这篇综述中，我们将重点关注模拟心脏细胞外基质（cECM）硬度的底物对于理解细胞外和细胞内环境之间生物力学串扰的相关性。适时调节这些途径的能力可能是调节体外 hiPSC-CM 成熟的关键。因此，hiPSC-CM 模型和基质硬度似乎都是研究 cECM-细胞相互作用的有趣工具。对这些机制的更多了解可能为 cECM 如何影响遗传心肌病中心脏细胞功能提供新的见解。
