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Disease modeling and lentiviral gene transfer in patient-specific induced pluripotent stem cells from late-onset Pompe disease patient.

Sato Y, Kobayashi H, Higuchi T, Shimada Y, Era T, Kimura S, Eto Y, Ida H, Ohashi T - Mol Ther Methods Clin Dev (2015)

Bottom Line: Lentiviral GAA rescue improves GAA enzyme activity and glycogen accumulation in iPSC.The efficacy of gene therapy is maintained following the cardiomyocyte differentiation.Lentiviral GAA transfer ameliorates the disease-specific change in cardiomyocyote.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, The Jikei University School of Medicine , Tokyo, Japan ; Division of Gene Therapy, Research Center for Medical Sciences, The Jikei University School of Medicine , Tokyo, Japan.

ABSTRACT
Pompe disease is an autosomal recessive inherited metabolic disease caused by deficiency of acid α-glucosidase (GAA). Glycogen accumulation is seen in the affected organ such as skeletal muscle, heart, and liver. Hypertrophic cardiomyopathy is frequently seen in the infantile onset Pompe disease. On the other hand, cardiovascular complication of the late-onset Pompe disease is considered as less frequent and severe than that of infantile onset. There are few investigations which show cardiovascular complication of late onset Pompe disease due to the shortage of appropriate disease model. We have generated late-onset Pompe disease-specific induced pluripotent stem cell (iPSC) and differentiated them into cardiomyocytes. Differentiated cardiomyocyte shows glycogen accumulation and lysosomal enlargement. Lentiviral GAA rescue improves GAA enzyme activity and glycogen accumulation in iPSC. The efficacy of gene therapy is maintained following the cardiomyocyte differentiation. Lentiviral GAA transfer ameliorates the disease-specific change in cardiomyocyote. It is suggested that Pompe disease iPSC-derived cardiomyocyte is replicating disease-specific changes in the context of disease modeling, drug screening, and cell therapy.

No MeSH data available.


Related in: MedlinePlus

Disease-specific change of Pompe disease iPSCs. (a) Mutation analysis shows compound heterozygote mutation (c.796 C>A and c.1316 T>A). (b) Electron microscopy of iPS cell lines (Pompe-1, Pompe2, Pompe3, and control). Arrow is demonstrating accumulated glycogen. Upper scale bar, 5 µm; lower scale bar, 1 µm. (c) GAA enzyme assay of iPS cell lines (Control, Pompe1, Pompe2, and Pompe3). Data were expressed as means ± SEM. (d) Glycogen assay of iPS cell lines (Control, Pompe1, Pompe2, and Pompe3). Data were expressed as means ± SEM.
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fig2: Disease-specific change of Pompe disease iPSCs. (a) Mutation analysis shows compound heterozygote mutation (c.796 C>A and c.1316 T>A). (b) Electron microscopy of iPS cell lines (Pompe-1, Pompe2, Pompe3, and control). Arrow is demonstrating accumulated glycogen. Upper scale bar, 5 µm; lower scale bar, 1 µm. (c) GAA enzyme assay of iPS cell lines (Control, Pompe1, Pompe2, and Pompe3). Data were expressed as means ± SEM. (d) Glycogen assay of iPS cell lines (Control, Pompe1, Pompe2, and Pompe3). Data were expressed as means ± SEM.

Mentions: Gene analysis showed compound heterozygote mutation, c.796C>T and c.1316T>A, which is corresponding to late onset Pompe disease (Figure 2a).


Disease modeling and lentiviral gene transfer in patient-specific induced pluripotent stem cells from late-onset Pompe disease patient.

Sato Y, Kobayashi H, Higuchi T, Shimada Y, Era T, Kimura S, Eto Y, Ida H, Ohashi T - Mol Ther Methods Clin Dev (2015)

Disease-specific change of Pompe disease iPSCs. (a) Mutation analysis shows compound heterozygote mutation (c.796 C>A and c.1316 T>A). (b) Electron microscopy of iPS cell lines (Pompe-1, Pompe2, Pompe3, and control). Arrow is demonstrating accumulated glycogen. Upper scale bar, 5 µm; lower scale bar, 1 µm. (c) GAA enzyme assay of iPS cell lines (Control, Pompe1, Pompe2, and Pompe3). Data were expressed as means ± SEM. (d) Glycogen assay of iPS cell lines (Control, Pompe1, Pompe2, and Pompe3). Data were expressed as means ± SEM.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4495721&req=5

fig2: Disease-specific change of Pompe disease iPSCs. (a) Mutation analysis shows compound heterozygote mutation (c.796 C>A and c.1316 T>A). (b) Electron microscopy of iPS cell lines (Pompe-1, Pompe2, Pompe3, and control). Arrow is demonstrating accumulated glycogen. Upper scale bar, 5 µm; lower scale bar, 1 µm. (c) GAA enzyme assay of iPS cell lines (Control, Pompe1, Pompe2, and Pompe3). Data were expressed as means ± SEM. (d) Glycogen assay of iPS cell lines (Control, Pompe1, Pompe2, and Pompe3). Data were expressed as means ± SEM.
Mentions: Gene analysis showed compound heterozygote mutation, c.796C>T and c.1316T>A, which is corresponding to late onset Pompe disease (Figure 2a).

Bottom Line: Lentiviral GAA rescue improves GAA enzyme activity and glycogen accumulation in iPSC.The efficacy of gene therapy is maintained following the cardiomyocyte differentiation.Lentiviral GAA transfer ameliorates the disease-specific change in cardiomyocyote.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, The Jikei University School of Medicine , Tokyo, Japan ; Division of Gene Therapy, Research Center for Medical Sciences, The Jikei University School of Medicine , Tokyo, Japan.

ABSTRACT
Pompe disease is an autosomal recessive inherited metabolic disease caused by deficiency of acid α-glucosidase (GAA). Glycogen accumulation is seen in the affected organ such as skeletal muscle, heart, and liver. Hypertrophic cardiomyopathy is frequently seen in the infantile onset Pompe disease. On the other hand, cardiovascular complication of the late-onset Pompe disease is considered as less frequent and severe than that of infantile onset. There are few investigations which show cardiovascular complication of late onset Pompe disease due to the shortage of appropriate disease model. We have generated late-onset Pompe disease-specific induced pluripotent stem cell (iPSC) and differentiated them into cardiomyocytes. Differentiated cardiomyocyte shows glycogen accumulation and lysosomal enlargement. Lentiviral GAA rescue improves GAA enzyme activity and glycogen accumulation in iPSC. The efficacy of gene therapy is maintained following the cardiomyocyte differentiation. Lentiviral GAA transfer ameliorates the disease-specific change in cardiomyocyote. It is suggested that Pompe disease iPSC-derived cardiomyocyte is replicating disease-specific changes in the context of disease modeling, drug screening, and cell therapy.

No MeSH data available.


Related in: MedlinePlus