Advances in human induced pluripotent stem cell (hiPSC)-based disease modelling in cardiogenetics.

IF 1.1 4区 生物学
Medizinische Genetik Pub Date : 2025-04-08 eCollection Date: 2025-06-01 DOI:10.1515/medgen-2025-2009
Sandra Hoffmann, Timon Seeger
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引用次数: 0

Abstract

Human induced pluripotent stem cell (hiPSC)-based disease modelling has significantly advanced the field of cardiogenetics, providing a precise, patient-specific platform for studying genetic causes of heart diseases. Coupled with genome editing technologies such as CRISPR/Cas, hiPSC-based models not only allow the creation of isogenic lines to study mutation-specific cardiac phenotypes, but also enable the targeted modulation of gene expression to explore the effects of genetic and epigenetic deficits at the cellular and molecular level. hiPSC-based models of heart disease range from two-dimensional cultures of hiPSC-derived cardiovascular cell types, such as various cardiomyocyte subtypes, endothelial cells, pericytes, vascular smooth muscle cells, cardiac fibroblasts, immune cells, etc., to cardiac tissue cultures including organoids, microtissues, engineered heart tissues, and microphysiological systems. These models are further enhanced by multi-omics approaches, integrating genomic, transcriptomic, epigenomic, proteomic, and metabolomic data to provide a comprehensive view of disease mechanisms. In particular, advances in cardiovascular tissue engineering enable the development of more physiologically relevant systems that recapitulate native heart architecture and function, allowing for more accurate modelling of cardiac disease, drug screening, and toxicity testing, with the overall goal of personalised medical approaches, where therapies can be tailored to individual genetic profiles. Despite significant progress, challenges remain in the maturation of hiPSC-derived cardiomyocytes and the complexity of reproducing adult heart conditions. Here, we provide a concise update on the most advanced methods of hiPSC-based disease modelling in cardiogenetics, with a focus on genome editing and cardiac tissue engineering.

基于人类诱导多能干细胞(hiPSC)的心脏遗传学疾病建模研究进展。
基于人类诱导多能干细胞(hiPSC)的疾病建模极大地推进了心脏遗传学领域,为研究心脏病的遗传原因提供了一个精确的、针对患者的平台。结合CRISPR/Cas等基因组编辑技术,基于hipsc的模型不仅可以创建等基因系来研究突变特异性心脏表型,还可以在细胞和分子水平上靶向调节基因表达,探索遗传和表观遗传缺陷的影响。基于hipsc的心脏病模型范围从hipsc衍生的心血管细胞类型的二维培养,如各种心肌细胞亚型、内皮细胞、周细胞、血管平滑肌细胞、心脏成纤维细胞、免疫细胞等,到心脏组织培养,包括类器官、微组织、工程化心脏组织和微生理系统。这些模型通过多组学方法进一步增强,整合基因组学、转录组学、表观基因组学、蛋白质组学和代谢组学数据,以提供疾病机制的全面视图。特别是,心血管组织工程的进步使更多生理相关系统的发展能够概括天然心脏结构和功能,允许更准确的心脏病建模,药物筛选和毒性测试,以个性化医疗方法的总体目标,其中治疗可以根据个人基因谱进行定制。尽管取得了重大进展,但hipsc来源的心肌细胞的成熟和再生成人心脏病的复杂性仍然存在挑战。在这里,我们提供了关于心脏遗传学中基于hipsc的疾病建模的最先进方法的简要更新,重点是基因组编辑和心脏组织工程。
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来源期刊
Medizinische Genetik
Medizinische Genetik GENETICS & HEREDITY-
自引率
9.10%
发文量
48
期刊介绍: medizinischegenetik is a scientific journal that is owned and published by the German Society of Human Genetics e.V. since 1989. The journal was founded by Prof. Jan Murken, München. Self-published until 2006, from 2007-2019 published at Springer Verlag and since 2020 at De Gruyter. medizinischegenetik serves education and training among colleagues, the interdisciplinary exchange of knowledge in all areas of human genetics in clinics, practice, research and teaching. Each issue of the quarterly journal deals with a focus that provides a comprehensive overview of current developments in specific clinical pictures, technical developments and therapeutic approaches. All reviews are written in English language. The journal thus creates a platform for the international exchange of knowledge and increased awareness of German research activities in the scientific community. In addition, medizinischegenetik contains information on activities in its own subject in the German-language section. This includes conference reports, association announcements, personnel matters, statements and guidelines. With health policy questions, historical retrospectives and comments on current developments, the profession takes a stand on human genetic issues in Germany, Austria and Switzerland.
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