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Mol Genet Metab. 2014 May;112(1):44-8. doi: 10.1016/j.ymgme.2014.02.012. Epub 2014 Mar 4.

The generation of induced pluripotent stem cells (iPSCs) from patients with infantile and late-onset types of Pompe disease and the effects of treatment with acid-α-glucosidase in Pompe's iPSCs.

Author information

1
Department of Genetic Diseases and Genomic Science, The Jikei University School of Medicine, Tokyo, Japan; Department of Gene Therapy, Research Center for Medical Sciences, The Jikei University School of Medicine, Tokyo, Japan.
2
Department of Genetic Diseases and Genomic Science, The Jikei University School of Medicine, Tokyo, Japan; Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan.
3
Stem Cell Bank, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
4
Department of Gene Therapy, Research Center for Medical Sciences, The Jikei University School of Medicine, Tokyo, Japan.
5
Department of Genetic Diseases and Genomic Science, The Jikei University School of Medicine, Tokyo, Japan; Department of Gene Therapy, Research Center for Medical Sciences, The Jikei University School of Medicine, Tokyo, Japan; Department of Pediatrics, The Jikei University School of Medicine, Tokyo, Japan.
6
Department of Genetic Diseases and Genomic Science, The Jikei University School of Medicine, Tokyo, Japan; Advanced Clinical Research Center, Institute of Neurological Diseases, Kanagawa, Japan.
7
Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan.
8
Department of Genetic Diseases and Genomic Science, The Jikei University School of Medicine, Tokyo, Japan; Advanced Clinical Research Center, Institute of Neurological Diseases, Kanagawa, Japan. Electronic address: yosh@sepia.ocn.ne.jp.

Abstract

Pompe disease (PD), which is also called glycogen storage disease type II (GSDII), is one of the lysosomal storage diseases (LSDs) caused by a deficiency in acid-α-glucosidase (GAA) in the lysosome and is characterized by the accumulation of glycogen in various cells. PD has been treated by enzyme replacement therapy (ERT). We generated induced pluripotent stem cells (iPSCs) from the cells of patients with infantile-type and late-onset-type PD using a retrovirus vector to deliver transgenes encoding four reprogramming factors, namely, OCT4, SOX2, c-MYC, and KLF4. We confirmed that the two types of PD-iPSCs exhibited an undifferentiated state, alkaline phosphatase staining, and the presence of SSEA-4, TRA-1-60, and TRA-1-81. The PD-iPSCs exhibited strong positive staining with Periodic acid-Schiff (PAS). Moreover, ultrastructural features of these iPSCs exhibited massive glycogen granules in the cytoplasm, particularly in the infantile-type but to a lesser degree in the late-onset type. Glycogen granules of the infantile-type iPSCs treated with rhGAA were markedly decreased in a dose-dependent manner. Human induced pluripotent stem cell provides an opportunity to build up glycogen storage of Pompe disease in vitro. It represents a promising resource to study disease mechanisms, screen new drug compounds and develop new therapies for Pompe disease.

KEYWORDS:

Acid-α-glucosidase; Pompe disease; Ultrastructure; iPS cell

PMID:
24642446
DOI:
10.1016/j.ymgme.2014.02.012
[Indexed for MEDLINE]
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