Energy utilization of induced pluripotent stem cell-derived cardiomyocyte in Fabry disease

Shih Jie Chou, Wen Chung Yu, Yuh Lih Chang, Wen Yeh Chen, Wei Chao Chang, Yueh Chien, Jiin Cherng Yen, Yung Yang Liu, Shih Jen Chen, Chien Ying Wang, Yu Han Chen, Dau Ming Niu, Shing Jong Lin, Jaw Wen Chen, Shih Hwa Chiou*, Hsin Bang Leu


研究成果: Article同行評審

27 引文 斯高帕斯(Scopus)


Background Fabry disease (FD) is a lysosomal storage disease in which glycosphingolipids (GB3) accumulate in organs of the human body, leading to idiopathic hypertrophic cardiomyopathy and target organ damage. Its pathophysiology is still poorly understood. Objectives We aimed to generate patient-specific induced pluripotent stem cells (iPSC) from FD patients presenting cardiomyopathy to determine whether the model could recapitulate key features of the disease phenotype and to investigate the energy metabolism in Fabry disease. Methods Peripheral blood mononuclear cells from a 30-year-old Chinese man with a diagnosis of Fabry disease, GLA gene (IVS4 + 919G > A) mutation were reprogrammed into iPSCs and differentiated into iPSC-CMs and energy metabolism was analyzed in iPSC-CMs. Results The FD-iPSC-CMs recapitulated numerous aspects of the FD phenotype including reduced GLA activity, cellular hypertrophy, GB3 accumulation and impaired contractility. Decreased energy metabolism with energy utilization shift to glycolysis was observed, but the decreased energy metabolism was not modified by enzyme rescue replacement (ERT) in FD-iPSCs-CMs. Conclusion This model provided a promising in vitro model for the investigation of the underlying disease mechanism and development of novel therapeutic strategies for FD. This potential remedy for enhancing the energetic network and utility efficiency warrants further study to identify novel therapies for the disease.

頁(從 - 到)255-263
期刊International Journal of Cardiology
出版狀態Published - 1 4月 2017


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