title: 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.
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.
authors.affiliation: 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.
authors.forename: Takashi
authors.initials: T
authors.lastname: Higuchi
authors.affiliation: 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.
authors.forename: Shiho
authors.initials: S
authors.lastname: Kawagoe
authors.affiliation: Stem Cell Bank, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Otsu
authors.affiliation: Department of Gene Therapy, Research Center for Medical Sciences, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Yohta
authors.initials: Y
authors.lastname: Shimada
authors.affiliation: 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.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kobayashi
authors.affiliation: 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.
authors.forename: Reimi
authors.initials: R
authors.lastname: Hirayama
authors.affiliation: Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Eto
authors.affiliation: 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.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ida
authors.affiliation: 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.
authors.forename: Toya
authors.initials: T
authors.lastname: Ohashi
authors.affiliation: Stem Cell Bank, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Nakauchi
authors.affiliation: 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.
authors.forename: Yoshikatsu
authors.initials: Y
authors.lastname: Eto
mesh_terms: D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000473:pathology; D006003:Glycogen / Q000378:metabolism*; D006009:Glycogen Storage Disease Type II / Q000473:pathology / Q000628:therapy*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000187:drug effects* / Q000473:pathology*; D000090062:Kruppel-Like Factor 4; D008954:Models, Biological; D012867:Skin / Q000166:cytology; D000520:alpha-Glucosidases / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D006003:Glycogen; D000520:alpha-Glucosidases
keywords: Acid-α-glucosidase; Pompe disease; Ultrastructure; iPS cell