Transplants of neurosphere cell suspensions from aged mice are functional in the mouse model of Parkinson's.
Neural stem cell therapy has the potential to treat neurodegenerative disorders. For Parkinson's disease (PD), the goal is to enhance the dopamine system sufficiently to restore the control of movement and motor activities. In consideration of autologous stem cell therapy for PD, it will be necessary to propagate the cells in most cases from aged brain tissue. We isolated cells from the subventricular zone (SVZ) in the brains of 1-year-old enhanced green fluorescent protein (GFP) mice and generated neurospheres in culture. Neurospheres yielding high numbers of neurons and astrocytes "de novo" were selected and cryopreserved before evaluating the efficacy of neurosphere cell suspensions transplanted to the 6-hydroxydopamine (6-OHDA) model of PD. In mice unilaterally lesioned with 6-OHDA, transplants of neurosphere cell suspensions to the striatum yielded astrocytes and tyrosine hydroxylase positive neurons that reduced or reversed the drug-induced behavioral circling response to amphetamine and apomorphine. Control mice without the cell suspensions showed no change in the motor behavior. Our results indicate that the SVZ in the aged mouse brain contains cells that can be expanded in the form of neurospheres, cryopreserved, re-expanded and then transplanted into the damaged dopamine system to generate functional cell progeny that offset the motor disturbances in the nigrostriatal system.
Meissner
Kelly K
KK
Department of Pathology and Molecular Medicine, Health Science Center, HSC 1R1, McMaster University, 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5.
Kirkham
David L
DL
Doering
Laurie C
LC
D000375:Aging / Q000502:physiology*; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001253:Astrocytes / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001526:Behavioral Symptoms / Q000628:therapy; D003342:Corpus Striatum / Q000166:cytology / Q000601:surgery; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D007839:Functional Laterality; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000150:complications / Q000209:etiology / Q000628:therapy*; D033581:Stem Cell Transplantation / Q000379:methods*; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D018491:Dopamine Agonists; D018765:Dopamine Uptake Inhibitors; D005904:Glial Fibrillary Acidic Protein; D016900:Neurofilament Proteins; D049452:Green Fluorescent Proteins; D016627:Oxidopamine; D000661:Amphetamine; D014446:Tyrosine 3-Monooxygenase; D001058:Apomorphine