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诱导多能干细胞在心肌病中的应用:推动疾病建模、治疗开发和再生治疗

Induced Pluripotent Stem Cells in Cardiomyopathy: Advancing Disease Modeling, Therapeutic Development, and Regenerative Therapy.

作者信息

Vo Quan Duy, Nakamura Kazufumi, Saito Yukihiro, Akagi Satoshi, Miyoshi Toru, Yuasa Shinsuke

机构信息

Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.

Center for Advanced Heart Failure, Okayama University Hospital, Okayama 700-8558, Japan.

出版信息

Int J Mol Sci. 2025 May 22;26(11):4984. doi: 10.3390/ijms26114984.

Abstract

Cardiomyopathies are a heterogeneous group of heart muscle diseases that can lead to heart failure, arrhythmias, and sudden cardiac death. Traditional animal models and in vitro systems have limitations in replicating the complex pathology of human cardiomyopathies. Induced pluripotent stem cells (iPSCs) offer a transformative platform by enabling the generation of patient-specific cardiomyocytes, thus opening new avenues for disease modeling, drug discovery, and regenerative therapy. This process involves reprogramming somatic cells into iPSCs and subsequently differentiating them into functional cardiomyocytes, which can be characterized using techniques such as electrophysiology, contractility assays, and gene expression profiling. iPSC-derived cardiomyocyte (iPSC-CM) platforms are also being explored for drug screening and personalized medicine, including high-throughput testing for cardiotoxicity and the identification of patient-tailored therapies. While iPSC-CMs already serve as valuable models for understanding disease mechanisms and screening drugs, ongoing advances in maturation and bioengineering are bringing iPSC-based therapies closer to clinical application. Furthermore, the integration of multi-omics approaches and artificial intelligence (AI) is enhancing the predictive power of iPSC models. iPSC-based technologies are paving the way for a new era of personalized cardiology, with the potential to revolutionize the management of cardiomyopathies through patient-specific insights and regenerative strategies.

摘要

心肌病是一组异质性的心肌疾病,可导致心力衰竭、心律失常和心源性猝死。传统的动物模型和体外系统在复制人类心肌病的复杂病理方面存在局限性。诱导多能干细胞(iPSC)提供了一个变革性平台,能够生成患者特异性的心肌细胞,从而为疾病建模、药物发现和再生治疗开辟了新途径。这个过程包括将体细胞重编程为iPSC,随后将它们分化为功能性心肌细胞,这些心肌细胞可以使用电生理学、收缩性测定和基因表达谱分析等技术进行表征。源自iPSC的心肌细胞(iPSC-CM)平台也正在用于药物筛选和个性化医疗的探索,包括心脏毒性的高通量测试以及患者定制疗法的识别。虽然iPSC-CM已经成为理解疾病机制和筛选药物的有价值模型,但在成熟度和生物工程方面的持续进展正在使基于iPSC的疗法更接近临床应用。此外,多组学方法和人工智能(AI)的整合正在增强iPSC模型的预测能力。基于iPSC的技术正在为个性化心脏病学的新时代铺平道路,有可能通过患者特异性的见解和再生策略彻底改变心肌病的管理。

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