The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Int J Neurosci. 2014 Jan;124(1):12-21. doi: 10.3109/00207454.2013.789514. Epub 2013 Nov 19.
The generation of disease-specific induced pluripotent stem cell (iPS cell) lines from patients with incurable diseases is a promising approach for studying disease mechanisms and for drug screening. Such innovation enables us to obtain autologous cell sources for regenerative medicine. Herein, we report the generation and characterization of iPS cells from the fibroblasts of patients with a family history of Duchenne muscular dystrophy (DMD); these fibroblasts were obtained from patients at 22 gestational weeks of age and exhibit exon duplication from exons 16 to 42. The DMD-iPS cells were generated by the ectopic expression of four transcription factors: OCT4, SOX2, KLF4, and c-MYC; the DMD-iPS cells expressed several pluripotency markers and could be differentiated into various somatic cell types both in vitro and in vivo. Furthermore, DMD-iPSCs showed the differentiation potential to neuronal lineage. Thus, DMD-iPS cells are expected to serve as an in vitro disease model system, which will lay a foundation for the production of autologous cell therapies that avoid immune rejection and enable the correction of gene defects prior to tissue reconstitution.
从无法治愈疾病的患者中生成特定疾病的诱导多能干细胞（iPS 细胞）系是研究疾病机制和药物筛选的一种很有前途的方法。这种创新使我们能够获得用于再生医学的自体细胞来源。在此，我们报告了从具有杜氏肌营养不良症（DMD）家族病史的患者的成纤维细胞中生成和表征 iPS 细胞；这些成纤维细胞是从 22 孕周的患者中获得的，并且表现出从外显子 16 到 42 的外显子重复。通过异位表达四个转录因子：OCT4、SOX2、KLF4 和 c-MYC 来生成 DMD-iPS 细胞；DMD-iPS 细胞表达了几种多能性标记物，并能在体外和体内分化为各种体细胞类型。此外，DMD-iPSCs 表现出向神经元谱系分化的潜能。因此，DMD-iPS 细胞有望成为体外疾病模型系统，为避免免疫排斥的自体细胞疗法的生产和在组织重建之前纠正基因缺陷奠定基础。
