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

WEN LI, Elisabet Englund, Håkan Widner, Bengt Mattsson, Danielle van Westen, Jimmy Lätt, Stig Rehncrona, Patrik Brundin, Anders Björklund, Olle Lindvall, Jia-Yi Li

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)6544-6549
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number23
DOIs
Publication statusPublished - 2016

Subject classification (UKÄ)

  • Neurology

Free keywords

  • Parkinson Disease

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