title: Treatment of Parkinson's disease model mice with allogeneic embryonic stem cells: necessity of immunosuppressive treatment for sustained improvement.
abstract: OBJECTIVE
  The purpose of the present study was to examine the efficacy of transplantation of mouse embryonic stem (ES) into Parkinson's disease (PD) model mice as well as the necessity of immunosuppression in allogeneic donor-host combinations.
  
  
  METHODS
  ES cells, derived from SvJ129 strain mice, were differentiated into tyrosine hydroxylase (TH)-positive neurons in vitro by an embryoid body (EB)-based multistep differentiation method and used as graft cells for PD mice, which were prepared by injection of 6-hydroxydopamine (OHDA) into C57BL/6, BALB/c and C3H/HeN strains. Mice from each strain were divided into Groups 1-3. Four weeks after the 6-OHDA injection, Group 1 received phosphate-buffered saline in the striatum wounds, while Group 2 received 2 x 10(4) graft cells, and Group 3 mice received 2 x 10(4) graft cells and were also treated with cyclosporine A.
  
  
  RESULTS
  Apomorphine-induced rotational behavior was improved in Groups 2 and 3, but not in Group 1. However, the behavioral improvement ceased later in Group 2, whereas sustained improvement was observed in Group 3 throughout the 8 week observation period after transplantation. ES-derived TH(+) cells were found at the grafted sites at the end of the experiment in Groups 2 and 3, and tended to be more abundant in Group 3.
  
  
  CONCLUSIONS
  Intra-striatum transplantation of ES-derived dopaminergic neurons was effective in treating PD mice, even in allogeneic donor-host combinations. Immunosuppressive treatment did not have an effect on initial behavioral restoration after transplantation; however, it was necessary for sustained improvement over a prolonged period.
authors.affiliation: Department of Neurosurgery, Nara Medical University, 840 Shijo-cho, Kashihara-shi, Nara 634-8521, Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Toriumi
authors.forename: Masahide
authors.initials: M
authors.lastname: Yoshikawa
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Matsuda
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Nishimura
authors.forename: Shu-Ichi
authors.initials: S
authors.lastname: Yamada
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Hirabayashi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakase
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Nonaka
authors.forename: Yukiteru
authors.initials: Y
authors.lastname: Ouji
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; D003342:Corpus Striatum / Q000033:anatomy & histology / Q000601:surgery; D016572:Cyclosporine / Q000008:administration & dosage*; D004195:Disease Models, Animal; D053595:Embryonic Stem Cells / Q000378:metabolism / Q000637:transplantation*; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects; D016627:Oxidopamine; D010300:Parkinson Disease / Q000628:therapy*; D033581:Stem Cell Transplantation / Q000379:methods; D013997:Time Factors; D014184:Transplantation, Homologous / Q000276:immunology / Q000379:methods*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D001058:Apomorphine