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

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

Research output: Contribution to journalArticle

63 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)202-213
Number of pages12
JournalExperimental and Molecular Medicine
Volume44
Issue number3
DOIs
Publication statusPublished - 2012 Jan 1
Externally publishedYes

Keywords

  • Biological
  • Drug evaluation
  • Drug screening
  • Induced pluripotent stem cells
  • Models
  • Preclinical
  • Tissue therapy

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

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  • Cite this

    Jang, J., Yoo, J. E., Lee, J. A., Lee, D. R., Kim, J. Y., Huh, Y. J., Kim, D-S., Park, C. Y., Hwang, D. Y., Kim, H. S., Kang, H. C., & Kim, D. W. (2012). Disease-specific induced pluripotent stem cells: A platform for human disease modeling and drug discovery. Experimental and Molecular Medicine, 44(3), 202-213. https://doi.org/10.3858/emm.2012.44.3.015