Reconstructing the heart using iPSCs: Engineering strategies and applications.

Reconstructing the heart using iPSCs: Engineering strategies and applications.
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DOI:
10.1016/j.yjmcc.2021.04.006
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发表时间:
2021-08
影响因子:
5
通讯作者:
Wu JC
Wu JC
中科院分区:
医学2区
文献类型:
--
作者:
Cho S;Lee C;Skylar-Scott MA;Heilshorn SC;Wu JC

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诱导多能干细胞(IPSCs)已成为心脏组织工程的重要组成部分,能够在由同基因细胞组装的人体3D组织模型中研究心血管疾病的机制、药物反应和发育过程。自从二十多年前第一批工程化心脏组织被引入以来,各种由IPSC衍生的心脏球体、器皿和心脏芯片模型已经开发出来,融合了最新的可用技术和材料。在这篇综述中,我们将首先概述形成心肌功能单位所需的基本生物构件,包括由可溶性因子(如小分子)分化的IPSC来源的细胞、细胞外基质支架和外源性生物物理成熟信号。然后,我们将总结不同的制造方法和策略,用于在不同的比例和几何形状的体外重建心脏。最后,我们将讨论这些平台如何随着可伸缩性和组织成熟度的不断提高,在未来为基础心血管研究和临床应用做出贡献。
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.
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