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干细胞技术在心脏再生中的应用:多能干细胞的承诺。

Stem Cell Technology in Cardiac Regeneration: A Pluripotent Stem Cell Promise.

机构信息

Translational Cardiomyology Laboratory, Stem Cell Institute Leuven, Stem Cell Biology and Embryology Unit, Department of Development and Regeneration, KU Leuven, 3000 Leuven, Belgium.

Translational Cardiomyology Laboratory, Stem Cell Institute Leuven, Stem Cell Biology and Embryology Unit, Department of Development and Regeneration, KU Leuven, 3000 Leuven, Belgium; Division of Human Anatomy, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, Italy.

出版信息

EBioMedicine. 2017 Feb;16:30-40. doi: 10.1016/j.ebiom.2017.01.029. Epub 2017 Jan 27.

Abstract

Despite advances in cardiovascular biology and medical therapy, heart disorders are the leading cause of death worldwide. Cell-based regenerative therapies become a promising treatment for patients affected by heart failure, but also underline the need for reproducible results in preclinical and clinical studies for safety and efficacy. Enthusiasm has been tempered by poor engraftment, survival and differentiation of the injected adult stem cells. The crucial challenge is identification and selection of the most suitable stem cell type for cardiac regenerative medicine. Human pluripotent stem cells (PSCs) have emerged as attractive cell source to obtain cardiomyocytes (CMs), with potential applications, including drug discovery and toxicity screening, disease modelling and innovative cell therapies. Lessons from embryology offered important insights into the development of stem cell-derived CMs. However, the generation of a CM population, uniform in cardiac subtype, adult maturation and functional properties, is highly recommended. Moreover, hurdles regarding tumorigenesis, graft cell death, immune rejection and arrhythmogenesis need to be overcome in clinical practice. Here we highlight the recent progression in PSC technologies for the regeneration of injured heart. We review novel strategies that might overcome current obstacles in heart regenerative medicine, aiming at improving cell survival and functional integration after cell transplantation.

摘要

尽管心血管生物学和医学治疗取得了进展,但心脏疾病仍是全球范围内的主要死亡原因。基于细胞的再生疗法成为心力衰竭患者的一种有前途的治疗方法,但也强调了在临床前和临床研究中需要可重复的结果,以确保安全性和有效性。由于注入的成年干细胞的植入、存活和分化效果不佳,人们的热情有所减退。关键的挑战是确定和选择最适合心脏再生医学的干细胞类型。人类多能干细胞 (PSCs) 已成为获得心肌细胞 (CMs) 的有吸引力的细胞来源,具有包括药物发现和毒性筛选、疾病建模和创新细胞治疗在内的潜在应用。胚胎学的经验教训为干细胞衍生的 CMs 的发展提供了重要的见解。然而,生成在心脏亚型、成人成熟和功能特性方面均匀的 CM 群体是非常必要的。此外,在临床实践中还需要克服致瘤性、移植物细胞死亡、免疫排斥和心律失常等障碍。在这里,我们重点介绍了用于损伤心脏再生的 PSC 技术的最新进展。我们回顾了可能克服心脏再生医学当前障碍的新策略,旨在提高细胞移植后的细胞存活和功能整合。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5183/5474503/ff5afe484107/gr1.jpg

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