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 w ith the limb contralateral to the MPTP injection was significantly imp aired following the lesion, Three monkeys received implants of polymer -encapsulated containing PC12 cells into the caudate nucleus and putam en. One monkey received identical implants of empty capsules and serve d as a control, After a transient improvement, limb use in the control monkey dissipated and returned to post-MPTP disability. Two of the th ree PC12 cell grafted monkeys recovered performance on the hand reach task to near normal levels for up to 6.5 mo posttransplantation. Capsu les retrieved from the monkeys who recovered limb function postimplant ation contained numerous viable PC12 cells that continued to release l evodopa, basal dopamine, and potassium evoked dopamine, In contrast, c apsules retrieved from the PC12 cell-grafted monkey which did not reco ver limb use on the hand reach task contained few cells which secreted negligible or undetectable levels of levodopa and dopamine. Interesti ngly, functional disability was not reinstated Following removal of th e capsules, Neuroanatomical and neurochemical evaluation of the grafte d striatum did not reveal a host-derived sprouting response of catecho laminergic or indolaminergic fibers, These data indicate that xenograf ts of PC12 cells can survive for up to 6.5 mo in nonimmunosuppressed m onkeys when immunoisolated via polymer encapsulation, Moreover, these cells continue to secrete high levels of levodopa and dopamine and ind uce recovery of motor function in parkinsonian nonhuman primates.