Human iPS cell-derived dopaminergic neurons function in a primate Parkinson’s disease model

DOI PDF Web Site Web Site 被引用文献70件 参考文献45件 オープンアクセス

書誌事項

公開日
2017-08
資源種別
journal article
権利情報
  • http://www.springer.com/tdm
DOI
  • 10.1038/nature23664
公開者
Springer Science and Business Media LLC

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説明

Induced pluripotent stem cells (iPS cells) are a promising source for a cell-based therapy to treat Parkinson's disease (PD), in which midbrain dopaminergic neurons progressively degenerate. However, long-term analysis of human iPS cell-derived dopaminergic neurons in primate PD models has never been performed to our knowledge. Here we show that human iPS cell-derived dopaminergic progenitor cells survived and functioned as midbrain dopaminergic neurons in a primate model of PD (Macaca fascicularis) treated with the neurotoxin MPTP. Score-based and video-recording analyses revealed an increase in spontaneous movement of the monkeys after transplantation. Histological studies showed that the mature dopaminergic neurons extended dense neurites into the host striatum; this effect was consistent regardless of whether the cells were derived from patients with PD or from healthy individuals. Cells sorted by the floor plate marker CORIN did not form any tumours in the brains for at least two years. Finally, magnetic resonance imaging and positron emission tomography were used to monitor the survival, expansion and function of the grafted cells as well as the immune response in the host brain. Thus, this preclinical study using a primate model indicates that human iPS cell-derived dopaminergic progenitors are clinically applicable for the treatment of patients with PD.

収録刊行物

  • Nature

    Nature 548 (7669), 592-596, 2017-08

    Springer Science and Business Media LLC

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