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Title: A Liver Model of Infantile-Onset Pompe Disease Using Patient-Specific Induced Pluripotent Stem Cells
Authors: Yoshida, Takeshi  kyouindb  KAKEN_id  orcid (unconfirmed)
Jonouchi, Tatsuya
Osafune, Kenji  kyouindb  KAKEN_id
Takita, Junko  kyouindb  KAKEN_id  orcid (unconfirmed)
Sakurai, Hidetoshi  kyouindb  KAKEN_id  orcid (unconfirmed)
Author's alias: 吉田, 健司
城之内, 達也
長船, 健二
滝田, 順子
櫻井, 英俊
Keywords: infantile-onset Pompe disease
iPS cell
enzyme replacement therapy
disease modeling
Issue Date: 29-Nov-2019
Publisher: Frontiers Media {SA}
Journal title: Frontiers in Cell and Developmental Biology
Volume: 7
Thesis number: 316
Abstract: Infantile-onset Pompe disease (IOPD) is a life-threatening multi-organ disease caused by an inborn defect of lysosomal acid α-glucosidase (GAA), which can degrade glycogen into glucose. Lack of GAA causes abnormal accumulation of glycogen in the lysosomes, particularly in the skeletal muscle, liver, and heart. Enzyme replacement therapy (ERT) with recombinant human GAA (rhGAA) is the only available treatment; however, its effect varies by organ. Thus, to fully understand the pathomechanism of IOPD, organ-specific disease models are necessary. We previously generated induced pluripotent stem cells (iPSCs) from three unrelated patients with IOPD and establish a skeletal muscle model of IOPD. Here, we used the same iPSC lines as the previous study and differentiated them into hepatocytes. As a result, hepatocytes differentiated from iPSC of IOPD patients showed abnormal accumulation of lysosomal glycogen, the hallmark of Pompe disease. Using this model, we also demonstrated that glycogen accumulation was dose-dependently restored by rhGAA treatment. In conclusion, we have successfully established an in vitro liver model of IOPD using patient-specific iPSCs. This model can be a platform to elucidate the underlying disease mechanism or to be applied to drug-screening. Moreover, our study also suggest that an iPSC-based approach is suitable for modeling of diseases that affect multiple organs like Pompe disease.
Rights: © 2019 Yoshida, Jonouchi, Osafune, Takita and Sakurai. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
DOI(Published Version): 10.3389/fcell.2019.00316
PubMed ID: 31850350
Appears in Collections:Journal Articles

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