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Disease-specific induced pluripotent stem cells: a platform for human disease modeling and drug discovery.

Authors
 Jiho Jang  ;  Jeong-Eun Yoo  ;  Jeong-Ah Lee  ;  Dongjin R. Lee  ;  Ji Young Kim  ;  Yong Jun Huh  ;  Dae-Sung Kim  ;  Chul-Yong Park  ;  Dong-Youn Hwang  ;  Han-Soo Kim  ;  Hoon-Chul Kang  ;  Dong-Wook Kim 
Citation
 EXPERIMENTAL AND MOLECULAR MEDICINE, Vol.44(3) : 202-213, 2012 
Journal Title
 EXPERIMENTAL AND MOLECULAR MEDICINE 
ISSN
 1226-3613 
Issue Date
2012
MeSH
Alzheimer Disease/genetics ; Alzheimer Disease/pathology* ; Cell Differentiation ; Cells, Cultured ; Diabetes Mellitus, Type 1/genetics ; Diabetes Mellitus, Type 1/pathology* ; Drug Discovery/methods* ; Fibroblasts/cytology ; Fibroblasts/metabolism ; Fibroblasts/pathology ; Gene Expression ; Humans ; Induced Pluripotent Stem Cells/cytology ; Induced Pluripotent Stem Cells/metabolism ; Induced Pluripotent Stem Cells/pathology* ; Muscular Dystrophy, Duchenne/genetics ; Muscular Dystrophy, Duchenne/pathology* ; Parkinson Disease/genetics ; Parkinson Disease/pathology*
Keywords
Alzheimer Disease/genetics ; Alzheimer Disease/pathology* ; Cell Differentiation ; Cells, Cultured ; Diabetes Mellitus, Type 1/genetics ; Diabetes Mellitus, Type 1/pathology* ; Drug Discovery/methods* ; Fibroblasts/cytology ; Fibroblasts/metabolism ; Fibroblasts/pathology ; Gene Expression ; Humans ; Induced Pluripotent Stem Cells/cytology ; Induced Pluripotent Stem Cells/metabolism ; Induced Pluripotent Stem Cells/pathology* ; Muscular Dystrophy, Duchenne/genetics ; Muscular Dystrophy, Duchenne/pathology* ; Parkinson Disease/genetics ; Parkinson Disease/pathology*
Abstract
The generation of disease-specific induced pluripotent stem cell (iPSC) lines from patients with incurable diseases is a promising approach for studying disease mechanisms and drug screening. Such innovation enables to obtain autologous cell sources in regenerative medicine. Herein, we report the generation and characterization of iPSCs from fibroblasts of patients with sporadic or familial diseases, including Parkinson's disease (PD), Alzheimer's disease (AD), juvenile-onset, type I diabetes mellitus (JDM), and Duchenne type muscular dystrophy (DMD), as well as from normal human fibroblasts (WT). As an example to modeling disease using disease-specific iPSCs, we also discuss the previously established childhood cerebral adrenoleukodystrophy (CCALD)- and adrenomyeloneuropathy (AMN)-iPSCs by our group. Through DNA fingerprinting analysis, the origins of generated disease-specific iPSC lines were identified. Each iPSC line exhibited an intense alkaline phosphatase activity, expression of pluripotent markers, and the potential to differentiate into all three embryonic germ layers: the ectoderm, endoderm, and mesoderm. Expression of endogenous pluripotent markers and downregulation of retrovirus-delivered transgenes [OCT4 (POU5F1), SOX2, KLF4, and c-MYC] were observed in the generated iPSCs. Collectively, our results demonstrated that disease-specific iPSC lines characteristically resembled hESC lines. Furthermore, we were able to differentiate PD-iPSCs, one of the disease-specific-iPSC lines we generated, into dopaminergic (DA) neurons, the cell type mostly affected by PD. These PD-specific DA neurons along with other examples of cell models derived from disease-specific iPSCs would provide a powerful platform for examining the pathophysiology of relevant diseases at the cellular and molecular levels and for developing new drugs and therapeutic regimens.
Files in This Item:
T201203961.pdf Download
DOI
22179105
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pediatrics (소아청소년과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Physiology (생리학교실) > 1. Journal Papers
Yonsei Authors
Kang, Hoon Chul(강훈철) ORCID logo https://orcid.org/0000-0002-3659-8847
Kim, Dae Sung(김대성)
Kim, Dong Wook(김동욱) ORCID logo https://orcid.org/0000-0002-5025-1532
Kim, Ji Young(김지영)
Kim, Han Soo(김한수)
Yoo, Jeong Eun(유정은)
Lee, Dongjin R.(이동진)
Lee, Jeong Ah(이정아)
Jang, Ji Ho(장지호) ORCID logo https://orcid.org/0000-0001-5551-3514
Huh, Yong Jun(허용준)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/90265
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