title: Potential use of embryonic stem cells for the treatment of mouse parkinsonian models: improved behavior by transplantation of in vitro differentiated dopaminergic neurons from embryonic stem cells.
abstract: BACKGROUND
  and Aims. The purpose of the present study was to examine the efficacy of transplantation of mouse embryonic-stem-(ES)-cell-derived tyrosine hydroxylase-positive (TH(+)) cells into Parkinsonian mice using behavioral tests and immunohistochemical evaluation.
  
  
  METHODS
  Undifferentiated ES cells carrying the enhanced green fluorescent protein (EGFP) gene were differentiated into a cell population containing TH(+) neurons using a five-step in vitro differentiation method. These ES-cell-derived cells were used as allografts in Parkinsonian mice, made by administering injections of 6-hydroxydopamine (6-OHDA). Fifteen hemiparkinsonian mice were divided into three groups. Four weeks after 6-OHDA injection, mice in groups 1, 2, and 3 received phosphate-buffered saline, 1 x 10(4) graft cells, and 1 x 10(5) graft cells, respectively, into their dopamine-denervated striata.
  
  
  RESULTS
  Improved rotational behavior was observed in the graft-transplanted groups (groups 2 and 3) 2 weeks after transplantation. Mice in group 2 displayed a continuous maintenance of reduced rotational behavior, while those in group 3 showed ipsilateral rotation toward the lesioned side at 4, 6, and 8 weeks after transplantation. Tumor formation was observed in one mouse in group 3. TH(+) cells were found at the grafted sites 8 weeks after transplantation in mice in groups 2 and 3, some of which were immunopositive to GFP, demonstrating the presence of dopaminergic neurons derived from the ES cells.
  
  
  CONCLUSIONS
  Transplantation of in vitro differentiated ES cells changed rotational behavior in Parkinsonian mice. Our results suggest the potential availability of ES cells for Parkinson's disease.
authors.affiliation: Department of Parasitology, Nara Medical University, Japan.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Nishimura
authors.forename: Masahide
authors.initials: M
authors.lastname: Yoshikawa
authors.forename: Seiji
authors.initials: S
authors.lastname: Kanda
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nonaka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yokota
authors.forename: Akira
authors.initials: A
authors.lastname: Shiroi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakase
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Hirabayashi
authors.forename: Yukiteru
authors.initials: Y
authors.lastname: Ouji
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Birumachi
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Ishizaka
authors.forename: Toshisuke
authors.initials: T
authors.lastname: Sakaki
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation; D002478:Cells, Cultured; D018491:Dopamine Agonists / Q000494:pharmacology; D049452:Green Fluorescent Proteins; D007150:Immunohistochemistry; D007202:Indicators and Reagents / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009474:Neurons / Q000637:transplantation*; D020734:Parkinsonian Disorders / Q000601:surgery*; D012399:Rotation; D013234:Stem Cells / Q000166:cytology*
chemical_list: D018491:Dopamine Agonists; D007202:Indicators and Reagents; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins; D001058:Apomorphine