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Original Article
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Volume 332:1118-1124 April 27, 1995 Number 17
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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.

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ABSTRACT

Background Trials are under way to determine whether fetal nigral grafts can improve motor function in patients with Parkinson's disease. Some studies use fluorodopa uptake on positron-emission tomography (PET) as a marker of graft viability, but fluorodopa uptake does not distinguish between host and grafted neurons. There has been no direct evidence that grafts of fetal tissue can survive and innervate the striatum.

Methods We studied a 59-year-old man with advanced Parkinson's disease who received bilateral grafts of fetal ventral mesencephalic tissue in the postcommissural putamen. The tissue came from seven embryos between 61/2 and 9 weeks after conception. The patient died 18 months later from a massive pulmonary embolism. The brain was studied with the use of tyrosine hydroxylase immunohistochemical methods.

Results After transplantation, the patient had sustained improvement in motor function and a progressive increase in fluorodopa uptake in the putamen on PET scanning. On examination of the brain, each of the large grafts appeared to be viable. Each was integrated into the host striatum and contained dense clusters of dopaminergic neurons. Processes from these neurons had grown out of the grafts and provided extensive dopaminergic reinnervation to the striatum in a patch-matrix pattern. Ungrafted regions of the putamen showed sparse dopaminergic innervation. We could not identify any sprouting of host dopaminergic processes.

Conclusions Grafts of fetal mesencephalic tissue can survive for a long period in the human brain and restore dopaminergic innervation to the striatum in patients with Parkinson's disease. In the patient we studied, clinical improvement and enhanced fluorodopa uptake on PET scanning were associated with the survival of the grafts and dopaminergic reinnervation of the striatum.


Source Information

From the Department of Neurological Sciences, Rush–Presbyterian–St. 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, Rush–Presbyterian–St. Luke's Medical Center, 2242 W. Harrison St., Chicago, IL 60612.

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Related Letters:

Transplantation of Fetal Mesencephalic Tissue in Parkinson's Disease
Freed C. R., Breeze R. E., Schneck S. A., Kordower J. H., Freeman T. B., Olanow C. W.
Extract | Full Text  
N Engl J Med 1995; 333:730-731, Sep 14, 1995. Correspondence

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