Yang Yuan, Yang Hao, Kiskin Fedir N, Zhang Joe Z
Institute of Neurological and Psychiatric Disorders, Shenzhen Bay Laboratory, Shenzhen, Guangdong Province, China.
Med Rev (2021). 2024 Feb 20;4(1):68-85. doi: 10.1515/mr-2023-0059. eCollection 2024 Feb.
Cardiovascular research has heavily relied on studies using patient samples and animal models. However, patient studies often miss the data from the crucial early stage of cardiovascular diseases, as obtaining primary tissues at this stage is impracticable. Transgenic animal models can offer some insights into disease mechanisms, although they usually do not fully recapitulate the phenotype of cardiovascular diseases and their progression. In recent years, a promising breakthrough has emerged in the form of three-dimensional (3D) cardiovascular models utilizing human pluripotent stem cells. These innovative models recreate the intricate 3D structure of the human heart and vessels within a controlled environment. This advancement is pivotal as it addresses the existing gaps in cardiovascular research, allowing scientists to study different stages of cardiovascular diseases and specific drug responses using human-origin models. In this review, we first outline various approaches employed to generate these models. We then comprehensively discuss their applications in studying cardiovascular diseases by providing insights into molecular and cellular changes associated with cardiovascular conditions. Moreover, we highlight the potential of these 3D models serving as a platform for drug testing to assess drug efficacy and safety. Despite their immense potential, challenges persist, particularly in maintaining the complex structure of 3D heart and vessel models and ensuring their function is comparable to real organs. However, overcoming these challenges could revolutionize cardiovascular research. It has the potential to offer comprehensive mechanistic insights into human-specific disease processes, ultimately expediting the development of personalized therapies.
心血管研究严重依赖于使用患者样本和动物模型的研究。然而，患者研究往往错过心血管疾病关键早期阶段的数据，因为在这个阶段获取原始组织是不切实际的。转基因动物模型可以提供一些关于疾病机制的见解，尽管它们通常不能完全重现心血管疾病的表型及其进展。近年来，利用人类多能干细胞的三维（3D）心血管模型取得了有前景的突破。这些创新模型在可控环境中重现了人类心脏和血管复杂的3D结构。这一进展至关重要，因为它弥补了心血管研究中的现有差距，使科学家能够使用源自人类的模型研究心血管疾病的不同阶段和特定药物反应。在本综述中，我们首先概述了用于生成这些模型的各种方法。然后，我们通过深入了解与心血管疾病相关的分子和细胞变化，全面讨论它们在研究心血管疾病中的应用。此外，我们强调了这些3D模型作为药物测试平台以评估药物疗效和安全性的潜力。尽管它们具有巨大潜力，但挑战依然存在，特别是在维持3D心脏和血管模型的复杂结构以及确保其功能与真实器官相当方面。然而，克服这些挑战可能会彻底改变心血管研究。它有可能提供对人类特定疾病过程的全面机制见解，最终加速个性化疗法的发展。
