Influence of cell preparation and target location on the behavioral recovery after striatal transplantation of fetal dopaminergic neurons in a primate model of Parkinson's disease.
Surgeries involving transplantation of fetal dopamine (DA) neurons into the caudate-putamen of patients with Parkinson's disease (PD) have been performed in various clinical trials to examine a potential restoration of motor function. The absence of studies in non-human primates to define the best transplantation protocols have lead to the use of a broad variety of techniques that potentially could have a major impact on the clinical outcome. The effects of using different cell and tissue preparation, and surgical targets, remain unknown. For this purpose, 20 St. Kitts African Green Monkeys (AFG) rendered parkinsonian by i.m. injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were balanced into 4 groups and unilaterally grafted in the (a) caudate or (b) putamen with fetal ventral mesencephalic (VM) tissue as (c) solid pieces or as a (d) cell suspension. By 9 months post-transplantation all animals showed significant and similar behavioral improvement as determined by a UPDRS based PD scale. Postmortem analyses showed that VM transplants survived in all animals. They were located in both surgical target sites, producing a broad DA reinnervation of the targeted nuclei that could also extend to the non-grafted nucleus on the ipsilateral side. Although no differences between groups were found in survival of DA neurons or degree of DA reinnervation, there was a significant correlation between striatal reinnervation and behavioral recovery only in animals transplanted in the putamen surgical target. Additionally, there was in general a stronger glial reaction to solid grafts than to cell suspensions. These studies provide data for the optimal time course, cell preparation and surgical targets for systematic examinations of both potential benefits and side effects of dopamine neuron cell transplantation in primate models of PD.
Redmond
D E
DE
St. Kitts Biomedical Research Foundation, St. Kitts, West Indies.
Vinuela
A
A
Kordower
J H
JH
Isacson
O
O
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D049109:Cell Proliferation; D002522:Chlorocebus aethiops; D003342:Corpus Striatum / Q000601:surgery*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D004622:Embryo, Mammalian; D005260:Female; D016332:Fetal Tissue Transplantation / Q000379:methods*; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D020734:Parkinsonian Disorders / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D011247:Pregnancy; D011897:Random Allocation; D020127:Recovery of Function / Q000502:physiology*; D013997:Time Factors
D009419:Nerve Tissue Proteins; D004298:Dopamine