Center for Stem Cell and Regenerative Medicine (CSCRM), The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (IMM), The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Cells. 2019 Jan 3;8(1):20. doi: 10.3390/cells8010020.
Induced pluripotent stem cells (iPSCs) are the foundation of modern stem cell-based regenerative medicine, especially in the case of degenerative disorders, such as muscular dystrophies (MDs). Since their introduction in 2006, many studies have used iPSCs for disease modeling and identification of involved mechanisms, drug screening, as well as gene correction studies. In the case of muscular dystrophies, these studies commenced in 2008 and continue to address important issues, such as defining the main pathologic mechanisms in different types of MDs, drug screening to improve skeletal/cardiac muscle cell survival and to slow down disease progression, and evaluation of the efficiency of different gene correction approaches, such as exon skipping, Transcription activator-like effector nucleases (TALENs), Zinc finger nucleases (ZFNs) and RNA-guided endonuclease Cas9 (CRISPR/Cas9). In the current short review, we have summarized chronological progress of these studies and their key findings along with a perspective on the future road to successful iPSC-based cell therapy for MDs and the potential hurdles in this field.
诱导多能干细胞(iPSCs)是现代基于干细胞的再生医学的基础,特别是在退行性疾病(如肌营养不良症)的情况下。自 2006 年问世以来,许多研究利用 iPSCs 进行疾病建模和发病机制的研究、药物筛选以及基因校正研究。在肌营养不良症的情况下,这些研究始于 2008 年,并且仍在继续解决重要问题,例如定义不同类型肌营养不良症的主要病理机制、筛选药物以提高骨骼肌/心肌细胞的存活率并减缓疾病进展,以及评估不同基因校正方法的效率,例如外显子跳跃、转录激活因子样效应物核酸酶(TALENs)、锌指核酸酶(ZFNs)和 RNA 指导的内切酶 Cas9(CRISPR/Cas9)。在当前的简短综述中,我们总结了这些研究的时间进展及其关键发现,并展望了基于 iPSC 的肌营养不良症细胞治疗的未来道路以及该领域的潜在障碍。