Jeziorowska Dorota, Korniat Agathe, Salem Joe-Elie, Fish Kenneth, Hulot Jean-Sébastien
a 1 UMRS_1166, ICAN , Paris, France.
b 2 Icahn School of Medicine at Mount Sinai, Cardiovascular Research Center , New York, NY, USA
Expert Opin Biol Ther. 2015;15(10):1399-409. doi: 10.1517/14712598.2015.1064109. Epub 2015 Jul 2.
Induced pluripotent stem cells (iPSC) represent an appealing cell source to develop disease-modeling assays, drug testing assays and cell-based replacement therapies especially for cardiac disorders.
The development of efficient protocols to generate pure populations of cardiac myocytes is a prerequisite to provide reproducible, robust and valid assays. Different techniques have been recently proposed that allow production of high-yield high-quality cardiomyocytes. In addition, the newly developed genome-editing techniques offer multiple opportunities to manipulate the genome of patient-specific iPSC thus generating syngeneic iPSC lines. Genome-editing techniques will also allow engineering of iPSC to make them suitable for replacement therapies.
Since their discovery, iPSCs have shown promise to revolutionize the way human diseases are studied. During the last years, different protocols have been developed to achieve reproducible and efficient differentiation of iPSCs including in cardiac and vascular cells. The recent introduction of the genome-editing techniques now allow targeted manipulation of the genome of patient-specific and control iPSCs lines. This approach would help to address a couple of current limitations, including the generation of isogenic lines for disease modeling and of clinical-grade lines for replacement therapy.
诱导多能干细胞(iPSC)是一种很有吸引力的细胞来源,可用于开发疾病建模分析、药物测试分析以及基于细胞的替代疗法,尤其是针对心脏疾病。
开发高效方案以生成纯心肌细胞群体是提供可重复、可靠且有效的分析方法的前提条件。最近提出了不同技术,可用于高产高质量心肌细胞的生产。此外,新开发的基因组编辑技术为操纵患者特异性iPSC的基因组提供了多种机会,从而产生同基因iPSC系。基因组编辑技术还将使iPSC的工程化成为可能,使其适用于替代疗法。
自发现以来,iPSC已显示出有望彻底改变人类疾病的研究方式。在过去几年中,已开发出不同方案以实现iPSC的可重复且高效分化,包括分化为心脏和血管细胞。基因组编辑技术的最新引入现在允许对患者特异性和对照iPSC系的基因组进行靶向操纵。这种方法将有助于解决当前的一些限制,包括用于疾病建模的同基因系的生成以及用于替代疗法的临床级系的生成。