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

Research output: Contribution to journalLetter

Abstract

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.

Details

Authors
  • Tetsuhiro Kikuchi
  • Asuka Morizane
  • Daisuke Doi
  • Hiroaki Magotani
  • Hirotaka Onoe
  • Takuya Hayashi
  • Hiroshi Mizuma
  • Sayuki Takara
  • Ryosuke Takahashi
  • Haruhisa Inoue
  • Satoshi Morita
  • Michio Yamamoto
  • Keisuke Okita
  • Masato Nakagawa
  • Malin Parmar
  • Jun Takahashi
Organisations
External organisations
  • Kyoto University
  • RIKEN Nishina Center for Accelerator-Based Science
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurosciences
Original languageEnglish
Pages (from-to)592-596
Number of pages5
JournalNature
Volume548
Issue number7669
Publication statusPublished - 2017 Aug 30
Publication categoryResearch
Peer-reviewedYes