Human Pompe disease-induced pluripotent stem cells for pathogenesis modeling, drug testing and disease marker identification

Hsiang Po Huang, Pin Hsun Chen, Wuh Liang Hwu, Ching Yu Chuang, Yin Hsiu Chien, Lee Stone, Chung Liang Chien, Li Tzu Li, Shu Chuan Chiang, Hsin Fu Chen, Hong Nerng Ho, Chung Hsuan Chen, Hung Chih Kuo

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)


Pompe disease is caused by autosomal recessive mutations in the acid alpha-glucosidase (GAA) gene, which encodes GAA. Although enzyme replacement therapy has recently improved patient survival greatly, the results in skeletal muscles and for advanced disease are still not satisfactory. Here, we report the derivation of Pompe disease-induced pluripotent stem cells (PomD-iPSCs) from two patients with different GAA mutations and their potential for pathogenesis modeling, drug testing and disease marker identification. PomD-iPSCs maintained pluripotent features and had low GAA activity and high glycogen content. Cardiomyocyte-like cells (CMLCs) differentiated from PomD-iPSCs recapitulated the hallmark Pompe disease pathophysiological phenotypes, including high levels of glycogen and multiple ultrastructural aberrances. Drug rescue assessment showed that exposure of PomD-iPSC-derived CMLCs to recombinant human GAA reversed the major pathologic phenotypes. Furthermore, l-carnitine treatment reduced defective cellular respiration in the diseased cells. By comparative transcriptome analysis, we identified glycogen metabolism, lysosome and mitochondria-related marker genes whose expression robustly correlated with the therapeutic effect of drug treatment in PomD-iPSC-derived CMLCs. Collectively, these results demonstrate that PomD-iPSCs are a promising in vitro disease model for the development of novel therapeutic strategies for Pompe disease.

Original languageEnglish
Article numberddr424
Pages (from-to)4851-4864
Number of pages14
JournalHuman Molecular Genetics
Issue number24
Publication statusPublished - Dec 1 2011
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)


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