公开(公告)号：US10287554B2

公开(公告)日：2019-05-14

申请号：US14839603

申请日：2015-08-28

Applicant: KOREA ADVANCED INSTITUTE OF SCIENCE AND TECHNOLOGY

Inventor： Yong-mahn Han ,  Sang-Wook Park

IPC: C12N5/074 ,  G01N33/50

Abstract: The present invention relates to an induced pluripotent stem cell model of Fabry disease, a preparation method thereof, and a use of the same for the study of Fabry disease development and for the screening of a therapeutic agent for the disease. Particularly, Fabry disease derived induced pluripotent stem cells (iPSCs), embryoid body (EB), and vascular cells were developed and differentiated from fibroblasts originated from Fabry disease patient, wherein the Fabry disease originated iPSCs displayed significantly reduced expression and activity of GLA protein therein, compared with the normal cells, resulting in the accumulation of globotriaosylceramide (Gb3, CD77). Also, the differentiation of vascular cells was induced from the Fabry disease originated iPSCs, and as a result the iPSCs were successfully differentiated into vascular endothelial cells and vascular smooth muscle cells with significantly expressing the marker protein. When the vascular endothelial cells and vascular smooth muscle cells were treated with Fabrazyme, the accumulation of Gb3 was significantly reduced, suggesting that the said cell model can be effectively used for the analysis/study of Fabry disease outbreak mechanism and for the screening of a therapeutic agent for the disease.

公开(公告)号：US20150361401A1

公开(公告)日：2015-12-17

申请号：US14839603

申请日：2015-08-28

Applicant: KOREA ADVANCED INSTITUTE OF SCIENCE AND TECHNOLOGY

Inventor： Yong-mahn Han ,  Sang-Wook Park

IPC: C12N5/074 ,  G01N33/50

CPC classification number: C12N5/0696 ,  C12N2501/602 ,  C12N2501/603 ,  C12N2501/604 ,  C12N2501/606 ,  C12N2506/1307 ,  G01N33/5064

Abstract: The present invention relates to an induced pluripotent stem cell model of Fabry disease, a preparation method thereof, and a use of the same for the study of Fabry disease development and for the screening of a therapeutic agent for the disease. Particularly, Fabry disease derived induced pluripotent stem cells (iPSCs), embryoid body (EB), and vascular cells were developed and differentiated from fibroblasts originated from Fabry disease patient, wherein the Fabry disease originated iPSCs displayed significantly reduced expression and activity of GLA protein therein, compared with the normal cells, resulting in the accumulation of globotriaosylceramide (Gb3, CD77). Also, the differentiation of vascular cells was induced from the Fabry disease originated iPSCs, and as a result the iPSCs were successfully differentiated into vascular endothelial cells and vascular smooth muscle cells with significantly expressing the marker protein. When the vascular endothelial cells and vascular smooth muscle cells were treated with Fabrazyme, the accumulation of Gb3 was significantly reduced, suggesting that the said cell model can be effectively used for the analysis/study of Fabry disease outbreak mechanism and for the screening of a therapeutic agent for the disease.

Abstract translation: 本发明涉及法布里病的诱导性多能干细胞模型及其制备方法，以及其用于研究法布里病发展和筛选疾病治疗剂的用途。 特别是，法布里病衍生的诱导多能干细胞（iPSCs），胚状体（EB）和血管细胞被开发并且来自法布里病患者的成纤维细胞分化，其中起源于法布里病的iPSCs显示出其中GLA蛋白的表达和活性显着降低 ，与正常细胞相比，导致球三孢神经酰胺（Gb3，CD77）的积累。 此外，从法布里病引起的iPSC诱导血管细胞的分化，结果iPSCs成功分化成血管内皮细胞和血管平滑肌细胞，并显着表达标记蛋白。 当用Fabrazyme处理血管内皮细胞和血管平滑肌细胞时，Gb3的积累显着降低，表明所述细胞模型可以有效地用于Fabry病爆发机制的分析/研究，以及用于筛选治疗 这种疾病的代理。