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: Takashi Higuchi, Shiho Kawagoe, Makoto Otsu, Yohta Shimada, Hiroshi Kobayashi, Reimi Hirayama, Koji Eto, Hiroyuki Ida, Toya Ohashi, Hiromitsu Nakauchi, Yoshikatsu Eto
• Journal: Molecular genetics and metabolism (Mol Genet Metab) Vol. 112 Issue 1 Pg. 44-8 (May 2014) ISSN: 1096-7206 [Electronic] United States
• PMID: 24642446 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• KLF4 protein, human
• Kruppel-Like Factor 4
• Glycogen
• alpha-Glucosidases

Topics

• Cell Line
• Dose-Response Relationship, Drug
• Fibroblasts (pathology)
• Glycogen (metabolism)
• Glycogen Storage Disease Type II (pathology, therapy)
• Humans
• Induced Pluripotent Stem Cells (drug effects, pathology)
• Kruppel-Like Factor 4
• Models, Biological
• Skin (cytology)
• alpha-Glucosidases (administration & dosage, pharmacology)