Neuropathological Evidence of Graft Survival and Striatal Reinnervation after the Transplantation of Fetal Mesencephalic Tissue in a Patient with Parkinson's Disease
Jeffrey H. Kordower, Ph.D., Thomas B. Freeman, M.D., Barry J. Snow, M.D., François J.G. Vingerhoets, M.D., Elliott J. Mufson, Ph.D., Paul R. Sanberg, Ph.D., Robert A. Hauser, M.D., Donald A. Smith, M.D., G. Michael Nauert, M.D., Daniel P. Perl, M.D., and C. Warren Olanow, M.D.
Background Trials are under way to determine whether fetal nigralgrafts can improve motor function in patients with Parkinson'sdisease. Some studies use fluorodopa uptake on positron-emissiontomography (PET) as a marker of graft viability, but fluorodopauptake does not distinguish between host and grafted neurons.There has been no direct evidence that grafts of fetal tissuecan survive and innervate the striatum.
Methods We studied a 59-year-old man with advanced Parkinson'sdisease who received bilateral grafts of fetal ventral mesencephalictissue in the postcommissural putamen. The tissue came fromseven embryos between 61/2 and 9 weeks after conception. Thepatient died 18 months later from a massive pulmonary embolism.The brain was studied with the use of tyrosine hydroxylase immunohistochemicalmethods.
Results After transplantation, the patient had sustained improvementin motor function and a progressive increase in fluorodopa uptakein the putamen on PET scanning. On examination of the brain,each of the large grafts appeared to be viable. Each was integratedinto the host striatum and contained dense clusters of dopaminergicneurons. Processes from these neurons had grown out of the graftsand provided extensive dopaminergic reinnervation to the striatumin a patch-matrix pattern. Ungrafted regions of the putamenshowed sparse dopaminergic innervation. We could not identifyany sprouting of host dopaminergic processes.
Conclusions Grafts of fetal mesencephalic tissue can survivefor a long period in the human brain and restore dopaminergicinnervation to the striatum in patients with Parkinson's disease.In the patient we studied, clinical improvement and enhancedfluorodopa uptake on PET scanning were associated with the survivalof the grafts and dopaminergic reinnervation of the striatum.
Source Information
From the Department of Neurological Sciences, RushPresbyterianSt. Luke's Medical Center, Chicago (J.H.K, E.J.M.); the Division of Neurosurgery (T.B.F., P.R.S., D.A.S.) and the Department of Neurology (R.A.H.), University of South Florida, Tampa; the Neurodegenerative Disorders Centre, University of British Columbia, Vancouver (B.J.S., F.J.G.V.); the Tampa Women's Health Center, Tampa, Fla. (G.M.N.); and the Departments of Pathology (D.P.P.) and Neurology (C.W.O.), Mount Sinai Medical Center, New York.
Address reprint requests to Dr. Kordower at the Department of Neurological Sciences, RushPresbyterianSt. Luke's Medical Center, 2242 W. Harrison St., Chicago, IL 60612.
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