Freedman Benjamin S
Division of Nephrology, Kidney Research Institute, and Institute for Stem Cell and Regenerative Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.
Biomark Insights. 2015 Dec 22;10(Suppl 1):153-69. doi: 10.4137/BMI.S20054. eCollection 2015.
Induced pluripotent stem cells (iPSCs) are somatic cells that have been transcriptionally reprogrammed to an embryonic stem cell (ESC)-like state. iPSCs are a renewable source of diverse somatic cell types and tissues matching the original patient, including nephron-like kidney organoids. iPSCs have been derived representing several kidney disorders, such as ADPKD, ARPKD, Alport syndrome, and lupus nephritis, with the goals of generating replacement tissue and 'disease in a dish' laboratory models. Cellular defects in iPSCs and derived kidney organoids provide functional, personalized biomarkers, which can be correlated with genetic and clinical information. In proof of principle, disease-specific phenotypes have been described in iPSCs and ESCs with mutations linked to polycystic kidney disease or focal segmental glomerulosclerosis. In addition, these cells can be used to model nephrotoxic chemical injury. Recent advances in directed differentiation and CRISPR genome editing enable more specific iPSC models and present new possibilities for diagnostics, disease modeling, therapeutic screens, and tissue regeneration using human cells. This review outlines growth opportunities and design strategies for this rapidly expanding and evolving field.
诱导多能干细胞（iPSC）是经过转录重编程后进入类似胚胎干细胞（ESC）状态的体细胞。iPSC是与原始患者相匹配的多种体细胞类型和组织的可再生来源，包括类肾单位肾脏类器官。已经获得了代表几种肾脏疾病的iPSC，如常染色体显性多囊肾病（ADPKD）、常染色体隐性多囊肾病（ARPKD）、阿尔波特综合征和狼疮性肾炎，目的是生成替代组织和“培养皿中的疾病”实验室模型。iPSC和衍生的肾脏类器官中的细胞缺陷提供了功能性的、个性化的生物标志物，这些生物标志物可以与遗传和临床信息相关联。在原理验证中，已经在与多囊肾病或局灶节段性肾小球硬化相关突变的iPSC和ESC中描述了疾病特异性表型。此外，这些细胞可用于模拟肾毒性化学损伤。定向分化和CRISPR基因组编辑方面的最新进展使得能够建立更具特异性的iPSC模型，并为使用人类细胞进行诊断、疾病建模、治疗筛选和组织再生带来了新的可能性。本综述概述了这一迅速扩展和发展的领域的发展机遇和设计策略。
