Neural stem cells. Biological features and therapeutic potential in Parkinson's disease.
OBJECTIVE
Neural stem cells (NSC) are clonogenic cells, capable of self-renewal and multilineage differentiation, since, under the appropriated experimental conditions, they proliferate indefinitely as undifferentiated neurospheres or differentiate in neurons, astrocytes and oligodendrocytes. Parkinson's disease is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons.


METHODS
Here we investigated the suitability of recently identified and characterized neuronal progenitor cells at eliciting functional recovery in unilateral 6HODA-lesioned mice. We describe herein that intrastriatal engraftment of stem cell-derived neurons isolated from the olfactory bulb to give rise dopaminergic-like neurons results in long lasting functional recovery in 6OHDA-injured mice.


RESULTS
Unilateral injection of 6OHDA resulted in a progressive neurodegeneration of the nigro-striatal pathway. Likewise, the systemic administration of L-DOPA in these mice elicited a marked contralateral turning which was evident 1 week post, increased during the following week and than stabilize throughout the time of the experiment. Conversely, the intrastriatal implantation of partially differentiated stem cells at 14 days postlesion, resulted in a profound decrease in L-DOPA-induced circling behavior; interestingly, the effect was evident 1 week after the engraftment and was retained during the following 9 weeks. Detailed biochemical and immunohistochemical evaluation is currently under investigation in our laboratory. Conclusion. Our observation opens new perspectives for the treatment of neurodegeneration in Parkinson's disease.
Parati
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Laboratory of Neurobiology, National Neurological Institute C. Besta, Milan, Italy. parati@istituto.besta.it
Bez
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Ponti
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Sala
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Pozzi
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Pagano
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D000818:Animals; D001973:Bromodeoxyuridine; D002454:Cell Differentiation; D007150:Immunohistochemistry; D051379:Mice; D008815:Mice, Inbred Strains; D009474:Neurons / Q000201:enzymology / Q000502:physiology / Q000637:transplantation*; D009830:Olfactory Bulb / Q000166:cytology; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000235:genetics / Q000473:pathology / Q000601:surgery*; D010641:Phenotype; D020127:Recovery of Function; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000473:pathology / Q000502:physiology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D001973:Bromodeoxyuridine