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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.
- Source :
-
Molecular genetics and metabolism [Mol Genet Metab] 2014 May; Vol. 112 (1), pp. 44-8. Date of Electronic Publication: 2014 Mar 04. - Publication Year :
- 2014
-
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.<br /> (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Subjects :
- Cell Line
Dose-Response Relationship, Drug
Fibroblasts pathology
Glycogen Storage Disease Type II pathology
Humans
Kruppel-Like Factor 4
Models, Biological
Skin cytology
alpha-Glucosidases pharmacology
Glycogen metabolism
Glycogen Storage Disease Type II therapy
Induced Pluripotent Stem Cells drug effects
Induced Pluripotent Stem Cells pathology
alpha-Glucosidases administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1096-7206
- Volume :
- 112
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Molecular genetics and metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 24642446
- Full Text :
- https://doi.org/10.1016/j.ymgme.2014.02.012