期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 113, 期 23, 页码 6544-6549出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1605245113
关键词
Parkinson's disease; transplantation; autopsy; synucleinopathy; reinnervation
资金
- Swedish Research Council
- BAGADILICO-Excellence in Parkinson and Huntington Research
- Swedish Parkinson Foundation
- Torsten Soderberg Foundation
- Strategic Research Area MultiPark (multidisciplinary research focus on Parkinson's disease at Lund University)
Clinical trials using cells derived from embryonic ventral mesencephalon have shown that transplanted dopaminergic neurons can survive and function in the long term, as demonstrated by in vivo brain imaging using F-18-fluorodopa and C-11-raclopride positron emission tomography. Here we report the postmortem analysis of a patient with Parkinson's disease who 24 y earlier underwent unilateral transplantation of embryonic dopaminergic neurons in the putamen and subsequently exhibited major motor improvement and recovery of striatal dopaminergic function. Histopathological analysis showed that a dense, near-normal graft-derived dopaminergic reinnervation of the putamen can be maintained for a quarter of a century despite severe host brain pathology and with no evidence of immune response. In addition, ubiquitin-and a-synuclein-positive inclusionswere seen, some with the appearance of typical Lewy bodies, in 11-12% of the grafted dopaminergic neurons, reflecting the spread of pathology from the host brain to the transplants. Because the clinical benefits induced by transplantation in this patient were gradually lost after 14 y posttransplantation, our findings provide the first reported evidence, to our knowledge, that even a viable dopaminergic graft giving rise to extensive striatal reinnervation may lose its efficacy if widespread degenerative changes develop in the host brain.
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