Journal
SYNAPSE
Volume 63, Issue 7, Pages 541-548Publisher
WILEY
DOI: 10.1002/syn.20634
Keywords
ES cell; PET; monkey; MPTP
Categories
Funding
- Ministry of Health, Labor and Welfare of Japan, Ministry of Education, Culture, Sports, Science and Technology of Japan (Special Coordination Funds), Japan Society for the Promotion of Science
- CREST
- Japan Science and Technology Agency (JST)
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The ability of primate embryonic stem (ES) cells to differentiate into dopamine (DA)-synthesizing neurons has raised hopes of creating novel cell therapies for Parkinson's disease (PD). As the primary purpose of cell transplantation in PD is restoration of dopaminergic neurotransmission in the striatum, in vivo assessment of DA function after grafting is necessary to achieve better therapeutic effects. A chronic model of PD was produced in two cynomolgus monkeys (M-1 and M-2) by systemic administration of neurotoxin. Neural stem cells (NSCs) derived from cynomolgus ES cells were implanted unilaterally in the putamen. To evaluate DA-specific functions, we used multiple [C-11]-labeled positron emission tomography (PET) tracers, including [beta-C-11]L-3,4-dihydroxyphenylalanine (L-[beta-C-11]DOPA, DA precursor ligand), [C-11]-2 beta-carbomethoxy3 beta-(4-fluorophenyl)tropane ([C-11]beta-CFT, DA transporter ligand) and [C-11]raclopride (D-2 receptor ligand). At 12 weeks after grafting NSCs, PET demonstrated significantly increased uptake of L-[beta-C-11]DOPA (M-1:41%, M-2:61%) and [C-11]beta-CFT (M-1:31%, M-2:36%) uptake in the grafted putamen. In addition, methamphetamine challenge in M-2 induced reduced [C-11]raclopride binding (16%) in the transplanted putamen, suggesting release of DA. These results show that transplantation of NSCs derived from cynomolgus monkey ES cells can restore DA function in the putamen of a primate model of PD. PET with multitracers is useful for functional studies in developing cell-based therapies against PD. Synapse 63:541-548, 2009. (C) 2009 Wiley-Liss, Inc.
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