Establishment of a basis for therapeutic treatment of chronic granulomatous disease using human induced pluripotent stem cells

我们尝试使用疾病特异性诱导多能干细胞（iPS细胞）来模拟慢性肉芽肿病。首先，我们利用基因组编辑技术从4名患者外周血中的T细胞和CYBB基因敲除的iPS细胞中产生患者特异性iPS细胞。CYBB基因敲除的iPS细胞可以分化为中性粒细胞，不能产生活性氧。然而，在本研究中，从CYBB基因敲除的iPS细胞分化的巨噬细胞或树突状细胞没有表现出任何显著的异常。考虑到iPS细胞的来源可能影响疾病模型化的结果，建立了从各种血细胞产生iPS细胞的系统。最后，还建立了利用腺相关病毒在iPS细胞中进行同源重组的系统。这些实验系统可以成为慢性肉芽肿性疾病治疗的平台。

We tried to model chronic granulomatous disease using disease-specific induced pluripotent stem cells (iPS cells). At first, we generated patient specific iPS cells from T cells in 4 patients' peripheral blood and CYBB gene knockout iPS cells by using genome editing technology. The CYBB knockout iPS cells could be differentiated into neutrophil that cannot generate reactive oxygen species. However, macrophage or dendritic cells differentiated from CYBB gene knockout iPS cells in this study did not exhibit any significant abnormality. With consideration for the possibility that the origin of iPS cells can affect results of disease modeling, a system for generating iPS cells from various blood cells was established. Finally, a system for homologous recombination in iPS cells using adeno-associated virus was also established. These experimental systems could be a platform for a therapeutic treatment of chronic granulomatous disease.