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Extensive graft-derived dopaminergic innervation is maintained 24 years after transplantation in the degenerating parkinsonian brain.

LI, WEN LU ; Englund, Elisabet LU ; Widner, Håkan LU ; Mattsson, Bengt LU ; van Westen, Danielle LU ; Lätt, Jimmy LU ; Rehncrona, Stig LU ; Brundin, Patrik; Björklund, Anders LU and Lindvall, Olle LU , et al. (2016) In Proceedings of the National Academy of Sciences of the United States of America 113(23). p.6544-6549
Abstract
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 18F-fluorodopa and 11C-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... (More)
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 18F-fluorodopa and 11C-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 α-synuclein–positive inclusions were 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. (Less)
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publication status
published
subject
keywords
Parkinson Disease
in
Proceedings of the National Academy of Sciences of the United States of America
volume
113
issue
23
pages
6 pages
publisher
National Academy of Sciences
external identifiers
  • Scopus:84973324671
  • WOS:000377155400056
ISSN
1091-6490
DOI
10.1073/pnas.1605245113
language
English
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yes
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bd102a2e-9c50-4422-8e45-4eebc8b810fd
date added to LUP
2016-05-17 09:39:22
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2017-02-26 04:38:36
@article{bd102a2e-9c50-4422-8e45-4eebc8b810fd,
  abstract     = {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 18F-fluorodopa and 11C-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 α-synuclein–positive inclusions were 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.},
  author       = {LI, WEN and Englund, Elisabet and Widner, Håkan and Mattsson, Bengt and van Westen, Danielle and Lätt, Jimmy and Rehncrona, Stig and Brundin, Patrik and Björklund, Anders and Lindvall, Olle and Li, Jia-Yi},
  issn         = {1091-6490},
  keyword      = {Parkinson Disease},
  language     = {eng},
  number       = {23},
  pages        = {6544--6549},
  publisher    = {National Academy of Sciences},
  series       = {Proceedings of the National Academy of Sciences of the United States of America},
  title        = {Extensive graft-derived dopaminergic innervation is maintained 24 years after transplantation in the degenerating parkinsonian brain.},
  url          = {http://dx.doi.org/10.1073/pnas.1605245113},
  volume       = {113},
  year         = {2016},
}