Isolation and transplantation of dopaminergic neurons generated from mouse embryonic stem cells

Takahito Yoshizaki, Motoki Inaji, Hiroko Kouike, Takuya Shimazaki, Kazunobu Sawamoto, Kiyoshi Ando, Isao Date, Kazuto Kobayashi, Tetsuya Suhara, Yasuo Uchiyama, Hideyuki Okano

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75 Citations (Scopus)

Abstract

Embryonic stem (ES) cells differentiate into dopamine (DA)-producing neurons when co-cultured with PA6 stromal cells, but the resulting cultures contain a variety of unidentified cells. In order to label live DA neurons in mixed populations, we introduced a GFP reporter under the control of the tyrosine hydroxylase (TH) gene promoter into ES cells. GFP expression was observed in TH-immunoreactive cells that differentiated from the ES cells that carried the TH-GFPreporter gene. DA neurons expressing GFP were sorted from the mixed cell population by fluorescence-activated cell sorting of cells exhibiting GFP fluorescence, and the sorted GFP+ cells obtained were transplanted into a rat model of Parkinson's disease. Some of these cells survived and innervated the host striatum, resulting in a partial recovery from parkinsonian behavioral defects. This strategy of isolation and transplantation of ES-cell-derived DA neurons should be useful for cellular and molecular studies of DA neurons and for clinical application in the treatment of Parkinson's disease.

Original languageEnglish
Pages (from-to)33-37
Number of pages5
JournalNeuroscience Letters
Volume363
Issue number1
DOIs
Publication statusPublished - 2004 Jun 3

Keywords

  • Dopamine neuron
  • Embryonic stem cells
  • Stromal-cell derived inducing activity (SDIA)
  • TH-GFP
  • Transplantation

ASJC Scopus subject areas

  • Neuroscience(all)

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  • Cite this

    Yoshizaki, T., Inaji, M., Kouike, H., Shimazaki, T., Sawamoto, K., Ando, K., Date, I., Kobayashi, K., Suhara, T., Uchiyama, Y., & Okano, H. (2004). Isolation and transplantation of dopaminergic neurons generated from mouse embryonic stem cells. Neuroscience Letters, 363(1), 33-37. https://doi.org/10.1016/j.neulet.2004.03.074