Partial recovery of dopaminergic pathway after graft of adult mesenchymal stem cells in a rat model of Parkinson's disease.
Cellular therapy with adult stem cells appears as an opportunity for treatment of Parkinson's disease. To validate this approach, we studied the effects of transplantation of rat adult bone-marrow mesenchymal stem cells in a rat model of Parkinson's disease. Animals were unilaterally lesioned in the striatum with 6-hydroxydopamine. Two weeks later, group I did not undergo grafting, group II underwent sham grafting, group III was intra-striatal grafted with cells cultured in an enriched medium and group IV was intra-striatal grafted with cells cultured in a standard medium. Rotational amphetamine-induced behavior was measured weekly until animals were killed 6 weeks later. One week after graft, the number of rotations/min was stably decreased by 50% in groups III and IV as compared with groups I and II. At 8 weeks post-lesion, the density of dopaminergic markers in the nerve terminals and cell bodies, i.e. immunoreactive tyrosine hydroxylase, membrane dopamine transporter and vesicular monoamine transporter-2 was significantly higher in group III as compared with group I. Moreover, using microdialysis studies, we observed that while the rate of pharmacologically induced release of dopamine was significantly reduced in lesioned versus intact striatum in no grafted rats, it was similar in both sides in animals transplanted with mesemchymal stem cells. These data demonstrate that graft of adult mesemchymal stem cells reduces behavioral effects induced by 6-hydroxydopamine lesion and partially restores the dopaminergic markers and vesicular striatal pool of dopamine. This cellular approach might be a restorative therapy in Parkinson's disease.
Bouchez
Gaëlle
G
INSERM U930, Laboratory Biophysique médicale & pharmaceutique, UFR Pharmacie, 31 avenue Monge, Tours, France.
Sensebé
Luc
L
Vourc'h
Patrick
P
Garreau
Lucette
L
Bodard
Sylvie
S
Rico
Angélique
A
Guilloteau
Denis
D
Charbord
Pierre
P
Besnard
Jean-Claude
JC
Chalon
Sylvie
S
D000818:Animals; D000963:Antimetabolites; D001522:Behavior, Animal / Q000502:physiology; D001973:Bromodeoxyuridine; D002478:Cells, Cultured; D017931:DNA Primers; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D017551:Microdialysis; D017072:Neostriatum / Q000502:physiology; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000503:physiopathology* / Q000628:therapy*; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D013378:Substantia Nigra / Q000502:physiology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism
D000963:Antimetabolites; D017931:DNA Primers; D050483:Dopamine Plasma Membrane Transport Proteins; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050493:Vesicular Monoamine Transport Proteins; D012313:RNA; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D001973:Bromodeoxyuridine; D004298:Dopamine