Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94025, USA; Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94025, USA.
Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94025, USA; Betty Irene Moore Children's Heart Center, Stanford Children's Health, Stanford, CA 94025, USA.
J Mol Cell Cardiol. 2021 Aug;157:56-65. doi: 10.1016/j.yjmcc.2021.04.006. Epub 2021 Apr 22.
Induced pluripotent stem cells (iPSCs) have emerged as a key component of cardiac tissue engineering, enabling studies of cardiovascular disease mechanisms, drug responses, and developmental processes in human 3D tissue models assembled from isogenic cells. Since the very first engineered heart tissues were introduced more than two decades ago, a wide array of iPSC-derived cardiac spheroids, organoids, and heart-on-a-chip models have been developed incorporating the latest available technologies and materials. In this review, we will first outline the fundamental biological building blocks required to form a functional unit of cardiac muscle, including iPSC-derived cells differentiated by soluble factors (e.g., small molecules), extracellular matrix scaffolds, and exogenous biophysical maturation cues. We will then summarize the different fabrication approaches and strategies employed to reconstruct the heart in vitro at varying scales and geometries. Finally, we will discuss how these platforms, with continued improvements in scalability and tissue maturity, can contribute to both basic cardiovascular research and clinical applications in the future.
诱导多能干细胞（iPSCs）已成为心脏组织工程的关键组成部分，使人们能够在源自同基因细胞的人类 3D 组织模型中研究心血管疾病机制、药物反应和发育过程。自二十多年前首次引入工程化心脏组织以来，已经开发出了广泛的 iPSC 衍生的心脏球体、类器官和芯片上心脏模型，这些模型结合了最新的可用技术和材料。在这篇综述中，我们首先概述形成功能性心肌单位所需的基本生物学构建块，包括通过可溶性因子（例如小分子）、细胞外基质支架和外源性生物物理成熟线索分化的 iPSC 衍生细胞。然后，我们将总结用于在不同尺度和几何形状上体外重建心脏的不同制造方法和策略。最后，我们将讨论这些平台如何在可扩展性和组织成熟度方面不断改进，为未来的基础心血管研究和临床应用做出贡献。
