Treatment of Parkinson's disease model mice with allogeneic embryonic stem cells: necessity of immunosuppressive treatment for sustained improvement.
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.
Toriumi
Hayato
H
Department of Neurosurgery, Nara Medical University, 840 Shijo-cho, Kashihara-shi, Nara 634-8521, Japan.
Yoshikawa
Masahide
M
Matsuda
Ryosuke
R
Nishimura
Fumihiko
F
Yamada
Shu-Ichi
S
Hirabayashi
Hidehiro
H
Nakase
Hiroyuki
H
Nonaka
Jun-Ichi
J
Ouji
Yukiteru
Y
Ishizaka
Shigeaki
S
Sakaki
Toshisuke
T
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
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D001058:Apomorphine