Differentiation and migration of long term expanded human neural progenitors in a partial lesion model of Parkinson's disease.
Human neural progenitor cells (HNPCs) can be expanded in large numbers for significant periods of time to provide a reliable source of neural cells for transplantation in neurodegenerative disorders such as Parkinson's disease (PD). In the present study, HNPCs isolated from embryonic cortex were expanded as neurospheres in cell culture for 10 months. Just prior to transplantation, a proportion of the HNPCs were treated in a "predifferentiation" protocol in combination with the neurotropic factor NT4, in order to yield significant numbers of neurons. For transplantation, either undifferentiated HNPCs, or predifferentiated HNPCs were transplanted into the substantia nigra of a rat model of Parkinson's disease. At 12 weeks, there was good survival with proliferation of transplanted HNPCs occurring after transplantation but ceasing before the animals were sacrificed. Transplants of predifferentiated cells contained a higher proportion of neurons. The presence of a lesion in the striatum had a significant influence on the migration of transplanted cells from the substantia nigra into the striatum. There was no significant behavioural recovery or effect of transplanted HNPCs on the loss of dopaminergic cells from the host brain. In conclusion, HNPCs may provide a source of cells for use in the treatment of Parkinson's disease.
Burnstein
Rowan M
RM
Cambridge Centre for Brain Repair, University of Cambridge, Forvie Site, Robinson Way, Cambridge CB2 2PY, UK.
Foltynie
Tom
T
He
Xiaoling
X
Menon
David K
DK
Svendsen
Clive N
CN
Caldwell
Maeve A
MA
D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002465:Cell Movement; D003342:Corpus Striatum / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D009414:Nerve Growth Factors / Q000494:pharmacology; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D016627:Oxidopamine / Q000378:metabolism; D010300:Parkinson Disease / Q000473:pathology / Q000628:therapy*; D051381:Rats; D011917:Rats, Inbred Lew; D018874:Spheroids, Cellular; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D013378:Substantia Nigra / Q000378:metabolism
D009414:Nerve Growth Factors; D016627:Oxidopamine; C073922:neurotrophin 4