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Pre-clinical study of induced pluripotent stem cell-derived dopaminergic progenitor cells for Parkinson’s disease

Author

Listed:
  • Daisuke Doi

    (Kyoto University)

  • Hiroaki Magotani

    (Kyoto University
    Shin Nippon Biomedical Laboratories, Ltd)

  • Tetsuhiro Kikuchi

    (Kyoto University)

  • Megumi Ikeda

    (Kyoto University
    Sumitomo Dainippon Pharma Co., Ltd)

  • Satoe Hiramatsu

    (Kyoto University
    Sumitomo Dainippon Pharma Co., Ltd)

  • Kenji Yoshida

    (Kyoto University
    Sumitomo Dainippon Pharma Co., Ltd)

  • Naoki Amano

    (Kyoto University)

  • Masaki Nomura

    (Kyoto University)

  • Masafumi Umekage

    (Kyoto University)

  • Asuka Morizane

    (Kyoto University)

  • Jun Takahashi

    (Kyoto University)

Abstract

Induced pluripotent stem cell (iPSC)-derived dopaminergic (DA) neurons are an expected source for cell-based therapies for Parkinson’s disease (PD). The regulatory criteria for the clinical application of these therapies, however, have not been established. Here we show the results of our pre-clinical study, in which we evaluate the safety and efficacy of dopaminergic progenitors (DAPs) derived from a clinical-grade human iPSC line. We confirm the characteristics of DAPs by in vitro analyses. We also verify that the DAP population include no residual undifferentiated iPSCs or early neural stem cells and have no genetic aberration in cancer-related genes. Furthermore, in vivo studies using immunodeficient mice reveal no tumorigenicity or toxicity of the cells. When the DAPs are transplanted into the striatum of 6-OHDA-lesioned rats, the animals show behavioral improvement. Based on these results, we started a clinical trial to treat PD patients in 2018.

Suggested Citation

  • Daisuke Doi & Hiroaki Magotani & Tetsuhiro Kikuchi & Megumi Ikeda & Satoe Hiramatsu & Kenji Yoshida & Naoki Amano & Masaki Nomura & Masafumi Umekage & Asuka Morizane & Jun Takahashi, 2020. "Pre-clinical study of induced pluripotent stem cell-derived dopaminergic progenitor cells for Parkinson’s disease," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17165-w
    DOI: 10.1038/s41467-020-17165-w
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    Cited by:

    1. Marco Luciani & Chiara Garsia & Stefano Beretta & Ingrid Cifola & Clelia Peano & Ivan Merelli & Luca Petiti & Annarita Miccio & Vasco Meneghini & Angela Gritti, 2024. "Human iPSC-derived neural stem cells displaying radial glia signature exhibit long-term safety in mice," Nature Communications, Nature, vol. 15(1), pages 1-24, December.
    2. Zhanna Alekseenko & José M. Dias & Andrew F. Adler & Mariya Kozhevnikova & Josina Anna Lunteren & Sara Nolbrant & Ashwini Jeggari & Svitlana Vasylovska & Takashi Yoshitake & Jan Kehr & Marie Carlén & , 2022. "Robust derivation of transplantable dopamine neurons from human pluripotent stem cells by timed retinoic acid delivery," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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