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基于三维 iPSC 的体外心脏模型在生物医学和药物研发中的应用。

Three-Dimensional iPSC-Based In Vitro Cardiac Models for Biomedical and Pharmaceutical Research Applications.

机构信息

Unit of Vascular Biology and Regenerative Medicine, Centro Cardiologico Monzino-IRCCS, 20138 Milan, Italy.

Department of Electronics, Information and Biomedical Engineering, Politecnico di Milano, 20133 Milan, Italy.

出版信息

Int J Mol Sci. 2024 Oct 4;25(19):10690. doi: 10.3390/ijms251910690.

Abstract

Cardiovascular diseases are a major cause of death worldwide. Advanced in vitro models can be the key stone for a better understanding of the mechanisms at the basis of the different pathologies, supporting the development of novel therapeutic protocols. In particular, the implementation of induced pluripotent stem cell (iPSC) technology allows for the generation of a patient-specific pluripotent cell line that is able to differentiate in several organ-specific cell subsets while retaining the patient genetic background, thus putting the basis for personalized in vitro modeling toward personalized medicine. The design of iPSC-based models able to recapitulate the complexity of the cardiac environment is a critical goal. Here, we review some of the published efforts to exploit three dimensional (3D) iPSC-based methods to recapitulate the relevant cardiomyopathies, including genetically and non-genetically determined cardiomyopathies and cardiotoxicity studies. Finally, we discuss the actual method limitations and the future perspectives in the field.

摘要

心血管疾病是全球范围内主要的死亡原因。先进的体外模型可能是更好地理解不同病理基础机制的关键,支持新型治疗方案的开发。特别是,诱导多能干细胞(iPSC)技术的实施允许生成能够在保留患者遗传背景的情况下分化为几种器官特异性细胞亚群的患者特异性多能细胞系,从而为个性化体外建模向个性化医学奠定基础。设计能够再现心脏环境复杂性的基于 iPSC 的模型是一个关键目标。在这里,我们回顾了一些已发表的利用基于三维(3D)iPSC 的方法来再现相关心肌病的努力,包括遗传和非遗传决定的心肌病以及心脏毒性研究。最后,我们讨论了该领域目前方法的局限性和未来展望。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7970/11477044/07d145d10e31/ijms-25-10690-g001.jpg

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