Encapsulated PC12 cell transplants into hemiparkinsonian monkeys: a behavioral, neuroanatomical, and neurochemical analysis.
Four cynomolgus monkeys were trained on a hand reaching task and then rendered hemiparkinsonian with an intracarotid injection of n-methyl 4 phenyl 1,2,3,6, tetrahydropyridine (MPTP). Performance on this task with the limb contralateral to the MPTP injection was significantly impaired following the lesion. Three monkeys received implants of polymer-encapsulated containing PC12 cells into the caudate nucleus and putamen. One monkey received identical implants of empty capsules and served as a control. After a transient improvement, limb use in the control monkey dissipated and returned to post-MPTP disability. Two of the three PC12 cell grafted monkeys recovered performance on the hand reach task to near normal levels for up to 6.5 mo posttransplantation. Capsules retrieved from the monkeys who recovered limb function postimplantation contained numerous viable PC12 cells that continued to release levodopa, basal dopamine, and potassium evoked dopamine. In contrast, capsules retrieved from the PC12 cell-grafted monkey which did not recover limb use on the hand reach task contained few cells which secreted negligible or undetectable levels of levodopa and dopamine. Interestingly, functional disability was not reinstated following removal of the capsules. Neuroanatomical and neurochemical evaluation of the grafted striatum did not reveal a host-derived sprouting response of catecholaminergic or indolaminergic fibers. These data indicate that xenografts of PC12 cells can survive for up to 6.5 mo in nonimmunosuppressed monkeys when immunoisolated via polymer encapsulation. Moreover, these cells continue to secrete high levels of levodopa and dopamine and induce recovery of motor function in parkinsonian nonhuman primates.
Kordower
J H
JH
Department of Neurological Sciences, Rush Presbyterian Medical Center, Chicago, IL 60612, USA.
Liu
Y T
YT
Winn
S
S
Emerich
D F
DF
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001522:Behavior, Animal; D002214:Capsules; D003342:Corpus Striatum / Q000737:chemistry / Q000473:pathology; D004298:Dopamine / Q000032:analysis; D000882:Haplorhini; D007150:Immunohistochemistry; D007980:Levodopa / Q000032:analysis; D008297:Male; D009043:Motor Activity; D016716:PC12 Cells / Q000378:metabolism / Q000637:transplantation*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000503:physiopathology / Q000601:surgery*; D051381:Rats; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D002214:Capsules; D007980:Levodopa; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine