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

2012 ◽  
Vol 21 (11) ◽  
pp. 2618-2618
Author(s):  
H.-P. Huang ◽  
P.-H. Chen ◽  
W.-L. Hwu ◽  
C.-Y. Chuang ◽  
Y.-H. Chien ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Pompe Disease ◽  
Drug Testing ◽  
Disease Marker ◽  
Induced Pluripotent ◽  
Marker Identification

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

2011 ◽  
Vol 20 (24) ◽  
pp. 4851-4864 ◽  
Author(s):  
Hsiang-Po Huang ◽  
Pin-Hsun Chen ◽  
Wuh-Liang Hwu ◽  
Ching-Yu Chuang ◽  
Yin-Hsiu Chien ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Pompe Disease ◽  
Drug Testing ◽  
Disease Marker ◽  
Induced Pluripotent ◽  
Marker Identification

scholarly journals Modeling CNS Involvement in Pompe Disease Using Neural Stem Cells Generated from Patient-Derived Induced Pluripotent Stem Cells

Cells ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 8
Author(s):  
Yu-Shan Cheng ◽  
Shu Yang ◽  
Junjie Hong ◽  
Rong Li ◽  
Jeanette Beers ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Pompe Disease ◽  
Drug Efficacy ◽  
Cns Involvement ◽  
Glycogen Accumulation ◽  
Induced Pluripotent ◽  
Alpha Glucosidase

Pompe disease is a lysosomal storage disorder caused by autosomal recessive mutations in the acid alpha-glucosidase (GAA) gene. Acid alpha-glucosidase deficiency leads to abnormal glycogen accumulation in patient cells. Given the increasing evidence of central nervous system (CNS) involvement in classic infantile Pompe disease, we used neural stem cells, differentiated from patient induced pluripotent stem cells, to model the neuronal phenotype of Pompe disease. These Pompe neural stem cells exhibited disease-related phenotypes including glycogen accumulation, increased lysosomal staining, and secondary lipid buildup. These morphological phenotypes in patient neural stem cells provided a tool for drug efficacy evaluation. Two potential therapeutic agents, hydroxypropyl-β-cyclodextrin and δ-tocopherol, were tested along with recombinant human acid alpha-glucosidase (rhGAA) in this cell-based Pompe model. Treatment with rhGAA reduced LysoTracker staining in Pompe neural stem cells, indicating reduced lysosome size. Additionally, treatment of diseased neural stem cells with the combination of hydroxypropyl-β-cyclodextrin and δ-tocopherol significantly reduced the disease phenotypes. These results demonstrated patient-derived Pompe neural stem cells could be used as a model to study disease pathogenesis, to evaluate drug efficacy, and to screen compounds for drug discovery in the context of correcting CNS defects.

scholarly journals Patient-specific hepatocyte-like cells derived from induced pluripotent stem cells model pazopanib-mediated hepatotoxicity

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Yukti Choudhury ◽  
Yi Chin Toh ◽  
Jiangwa Xing ◽  
Yinghua Qu ◽  
Jonathan Poh ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Drug Testing ◽  
Kinase Inhibitor ◽  
Patient Specific ◽  
Drug Induced ◽  
Clinical Phenotypes ◽  
Induced Pluripotent

Abstract Idiosyncratic drug-induced hepatotoxicity is a major cause of liver damage and drug pipeline failure, and is difficult to study as patient-specific features are not readily incorporated in traditional hepatotoxicity testing approaches using population pooled cell sources. Here we demonstrate the use of patient-specific hepatocyte-like cells (HLCs) derived from induced pluripotent stem cells for modeling idiosyncratic hepatotoxicity to pazopanib (PZ), a tyrosine kinase inhibitor drug associated with significant hepatotoxicity of unknown mechanistic basis. In vitro cytotoxicity assays confirmed that HLCs from patients with clinically identified hepatotoxicity were more sensitive to PZ-induced toxicity than other individuals, while a prototype hepatotoxin acetaminophen was similarly toxic to all HLCs studied. Transcriptional analyses showed that PZ induces oxidative stress (OS) in HLCs in general, but in HLCs from susceptible individuals, PZ causes relative disruption of iron metabolism and higher burden of OS. Our study establishes the first patient-specific HLC-based platform for idiosyncratic hepatotoxicity testing, incorporating multiple potential causative factors and permitting the correlation of transcriptomic and cellular responses to clinical phenotypes. Establishment of patient-specific HLCs with clinical phenotypes representing population variations will be valuable for pharmaceutical drug testing.

scholarly journals Erratum: Corrigendum: Colonic organoids derived from human induced pluripotent stem cells for modeling colorectal cancer and drug testing

2018 ◽  
Vol 24 (4) ◽  
pp. 526-526
Author(s):  
Miguel Crespo ◽  
Eduardo Vilar ◽  
Su-Yi Tsai ◽  
Kyle Chang ◽  
Sadaf Amin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Drug Testing ◽  
Induced Pluripotent
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