title: Disease-specific induced pluripotent stem cells: a platform for human disease modeling and drug discovery.
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.
authors.affiliation: Department of Physiology, Brain Korea 21 Project for Medical Science and Severance Biomedical Science Institute, Yonsei University College of Medicine,Seoul 120-752, Korea.
authors.forename: Jiho
authors.initials: J
authors.lastname: Jang
authors.forename: Jeong-Eun
authors.initials: JE
authors.lastname: Yoo
authors.forename: Jeong-Ah
authors.initials: JA
authors.lastname: Lee
authors.forename: Dongjin R
authors.initials: DR
authors.lastname: Lee
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Yong Jun
authors.initials: YJ
authors.lastname: Huh
authors.forename: Dae-Sung
authors.initials: DS
authors.lastname: Kim
authors.forename: Chul-Yong
authors.initials: CY
authors.lastname: Park
authors.forename: Dong-Youn
authors.initials: DY
authors.lastname: Hwang
authors.forename: Han-Soo
authors.initials: HS
authors.lastname: Kim
authors.forename: Hoon-Chul
authors.initials: HC
authors.lastname: Kang
authors.forename: Dong-Wook
authors.initials: DW
authors.lastname: Kim
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000473:pathology*; D055808:Drug Discovery / Q000379:methods*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D000090062:Kruppel-Like Factor 4; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics / Q000473:pathology*; D010300:Parkinson Disease / Q000235:genetics / Q000473:pathology*