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诱导多能干细胞衍生的生物起搏器——从实验台到临床应用

iPSC-Derived Biological Pacemaker-From Bench to Bedside.

作者信息

Vo Quan Duy, Nakamura Kazufumi, Saito Yukihiro, Iida Toshihiro, Yoshida Masashi, Amioka Naofumi, 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

Cells. 2024 Dec 11;13(24):2045. doi: 10.3390/cells13242045.

Abstract

Induced pluripotent stem cell (iPSC)-derived biological pacemakers have emerged as an alternative to traditional electronic pacemakers for managing cardiac arrhythmias. While effective, electronic pacemakers face challenges such as device failure, lead complications, and surgical risks, particularly in children. iPSC-derived pacemakers offer a promising solution by mimicking the sinoatrial node's natural pacemaking function, providing a more physiological approach to rhythm control. These cells can differentiate into cardiomyocytes capable of autonomous electrical activity, integrating into heart tissue. However, challenges such as achieving cellular maturity, long-term functionality, and immune response remain significant barriers to clinical translation. Future research should focus on refining gene-editing techniques, optimizing differentiation, and developing scalable production processes to enhance the safety and effectiveness of these biological pacemakers. With further advancements, iPSC-derived pacemakers could offer a patient-specific, durable alternative for cardiac rhythm management. This review discusses key advancements in differentiation protocols and preclinical studies, demonstrating their potential in treating dysrhythmias.

摘要

诱导多能干细胞(iPSC)衍生的生物起搏器已成为治疗心律失常的传统电子起搏器的替代方案。尽管电子起搏器有效,但面临诸如设备故障、导线并发症和手术风险等挑战,尤其是在儿童中。iPSC衍生的起搏器通过模拟窦房结的自然起搏功能提供了一个有前景的解决方案,为节律控制提供了一种更符合生理的方法。这些细胞可以分化为能够自主产生电活动的心肌细胞,并整合到心脏组织中。然而,实现细胞成熟、长期功能和免疫反应等挑战仍然是临床转化的重大障碍。未来的研究应专注于改进基因编辑技术、优化分化以及开发可扩展的生产工艺,以提高这些生物起搏器的安全性和有效性。随着进一步的进展,iPSC衍生的起搏器可为心律管理提供针对患者的、持久的替代方案。本综述讨论了分化方案和临床前研究的关键进展,展示了它们在治疗心律失常方面的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dca2/11674228/6d4e959e9f39/cells-13-02045-g001.jpg

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