研究动态
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三维心脏模型:临床前测试平台。

Three-dimensional cardiac models: a pre-clinical testing platform.

发表日期:2024 May 23
作者: Eline Groen, Christine L Mummery, Loukia Yiangou, Richard P Davis
来源: Stem Cell Research & Therapy

摘要:

近年来,人类多能干细胞(hPSC)技术的重大进步为心血管研究提供了宝贵的工具。特别是多细胞型 3 维 (3D) 心脏模型为动物研究提供了补充方法,这些方法比分化 hPSC 的简单二维 (2D) 培养物具有更好的代表性。这些人体 3D 心脏模型大致可分为两类:即通过聚集预分化细胞产生的细胞和在体外从 hPSC 分化过程中形成自组织结构的细胞。这些模型可以复制心脏发育的各个方面,也可以检查组成细胞类型之间的相互作用,其中一些模型与 2D 系统相比显示出更高的成熟度。这两个小组已经成为研究心脏病机制的生理相关临床前平台,展示了人类心脏的关键功能属性。在这篇综述中,我们描述了源自 hPSC 的不同心脏类器官模型、其生成方法、在心血管疾病研究中的应用以及在药物筛选中的用途。我们还解决了它们目前作为临床前测试平台的局限性和挑战,并提出了潜在的改进方案,以提高它们在心脏药物发现方面的功效。© 2024 作者。
Major advancements in human pluripotent stem cell (hPSC) technology over recent years have yielded valuable tools for cardiovascular research. Multi-cell type 3-dimensional (3D) cardiac models in particular, are providing complementary approaches to animal studies that are better representatives than simple 2-dimensional (2D) cultures of differentiated hPSCs. These human 3D cardiac models can be broadly divided into two categories; namely those generated through aggregating pre-differentiated cells and those that form self-organizing structures during their in vitro differentiation from hPSCs. These models can either replicate aspects of cardiac development or enable the examination of interactions among constituent cell types, with some of these models showing increased maturity compared with 2D systems. Both groups have already emerged as physiologically relevant pre-clinical platforms for studying heart disease mechanisms, exhibiting key functional attributes of the human heart. In this review, we describe the different cardiac organoid models derived from hPSCs, their generation methods, applications in cardiovascular disease research and use in drug screening. We also address their current limitations and challenges as pre-clinical testing platforms and propose potential improvements to enhance their efficacy in cardiac drug discovery.© 2024 The Author(s).