Disease-specific induced pluripotent stem cells: a platform for human disease modeling and drug discovery
Autor: | Jeong Eun Yoo, Ji-Young Kim, Han Soo Kim, Jeong Ah Lee, Hoon Chul Kang, Dong-Wook Kim, Dong-Youn Hwang, Chul-Yong Park, Dongjin R. Lee, Jiho Jang, Yong Jun Huh, Dae Sung Kim |
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Rok vydání: | 2011 |
Předmět: |
Cell type
induced pluripotent stem cells Cellular differentiation Clinical Biochemistry Gene Expression Biology Biochemistry Regenerative medicine Kruppel-Like Factor 4 SOX2 Alzheimer Disease Drug Discovery medicine Humans drug screening Induced pluripotent stem cell drug evaluation preclinical Molecular Biology Cells Cultured models biological Cell Differentiation Parkinson Disease tissue therapy Fibroblasts Muscular Dystrophy Duchenne medicine.anatomical_structure Diabetes Mellitus Type 1 KLF4 Immunology Cancer research Molecular Medicine Original Article Endoderm Stem cell |
Zdroj: | Experimental & Molecular Medicine |
ISSN: | 2092-6413 |
Popis: | 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. |
Databáze: | OpenAIRE |
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