心血管研究的新时代:利用碟中三维模型彻底改变心血管研究。

Medical review (Berlin, Germany) Pub Date : 2024-02-20 eCollection Date: 2024-02-01 DOI:10.1515/mr-2023-0059
Yuan Yang, Hao Yang, Fedir N Kiskin, Joe Z Zhang
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引用次数: 0

摘要

心血管研究在很大程度上依赖于使用病人样本和动物模型进行的研究。然而,病人研究往往会错过心血管疾病关键的早期阶段的数据,因为在这一阶段获取原始组织是不切实际的。转基因动物模型虽然通常不能完全再现心血管疾病的表型及其发展过程,但也能为疾病机制提供一些见解。近年来,利用人体多能干细胞的体外三维(3D)心血管模型取得了突破性进展。这些创新模型在受控环境中再现了人类心脏和血管错综复杂的三维结构。这一进步至关重要,因为它解决了心血管研究中的现有空白,使科学家们能够利用人类来源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,我们首先概述了生成这些模型的各种方法。然后,我们全面讨论了这些模型在心血管疾病研究中的应用,深入探讨了与心血管疾病相关的分子和细胞变化。此外,我们还强调了这些三维模型作为药物测试平台以评估药物疗效和安全性的潜力。尽管三维心脏和血管模型潜力巨大,但挑战依然存在,特别是在维护三维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,克服这些挑战可以彻底改变心血管研究。它有可能为人类特异性疾病过程提供全面的机理见解,最终加快个性化疗法的开发。
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The new era of cardiovascular research: revolutionizing cardiovascular research with 3D models in a dish.

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 in vitro 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.

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