Department of Anatomy and Embryology, Leiden University Medical Center, Leiden 2333ZA, the Netherlands.
Department of Anatomy and Embryology, Leiden University Medical Center, Leiden 2333ZA, the Netherlands; Department of Applied Stem Cell Technologies, University of Twente, Enschede 7500AE, the Netherlands.
Stem Cell Reports. 2021 Sep 14;16(9):2049-2057. doi: 10.1016/j.stemcr.2020.11.013. Epub 2020 Dec 18.
Human heart (patho)physiology is now widely studied using human pluripotent stem cells, but the immaturity of derivative cardiomyocytes has largely limited disease modeling to conditions associated with mutations in cardiac ion channel genes. Recent advances in tissue engineering and organoids have, however, created new opportunities to study diseases beyond "channelopathies." These synthetic cardiac structures allow quantitative measurement of contraction, force, and other biophysical parameters in three-dimensional configurations, in which the cardiomyocytes in addition become more mature. Multiple cardiac-relevant cell types are also often combined to form organized cardiac tissue mimetic constructs, where cell-cell, cell-extracellular matrix, and paracrine interactions can be mimicked. In this review, we provide an overview of some of the most promising technologies being implemented specifically in personalized heart-on-a-chip models and explore their applications, drawbacks, and potential for future development.
目前，人们广泛使用人类多能干细胞来研究人类心脏（病理）生理学，但衍生的心肌细胞的不成熟在很大程度上限制了疾病模型的建立，只能用于与心脏离子通道基因突变相关的疾病。然而，组织工程和类器官的最新进展为研究超越“通道病”的疾病创造了新的机会。这些合成心脏结构允许在三维构型中定量测量收缩、力和其他生物物理参数，其中心肌细胞也变得更加成熟。多种与心脏相关的细胞类型通常也组合在一起，形成有组织的心脏组织模拟构建体，其中可以模拟细胞-细胞、细胞-细胞外基质和旁分泌相互作用。在这篇综述中，我们提供了一些最有前途的技术的概述，这些技术专门应用于个性化的芯片上心脏模型，并探讨了它们的应用、缺点和未来发展的潜力。
