title: Extensive graft-derived dopaminergic innervation is maintained 24 years after transplantation in the degenerating parkinsonian brain.
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 (18)F-fluorodopa and (11)C-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.
authors.affiliation: Neural Plasticity and Repair Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, 221 84 Lund, Sweden;
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.affiliation: Division of Oncology and Pathology, Lund University Hospital, 221 85 Lund, Sweden;
authors.forename: Elisabet
authors.initials: E
authors.lastname: Englund
authors.affiliation: Division of Neurology, Lund University Hospital, 221 85 Lund, Sweden;
authors.forename: Håkan
authors.initials: H
authors.lastname: Widner
authors.affiliation: Neurobiology Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, 221 84 Lund, Sweden;
authors.forename: Bengt
authors.initials: B
authors.lastname: Mattsson
authors.affiliation: Center for Medical Imaging and Physiology, Lund University Hospital, 221 85 Lund, Sweden;
authors.forename: Danielle
authors.initials: D
authors.lastname: van Westen
authors.affiliation: Center for Medical Imaging and Physiology, Lund University Hospital, 221 85 Lund, Sweden;
authors.forename: Jimmy
authors.initials: J
authors.lastname: Lätt
authors.affiliation: Division of Neurosurgery, Lund University Hospital, 221 85 Lund, Sweden;
authors.forename: Stig
authors.initials: S
authors.lastname: Rehncrona
authors.affiliation: Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, MI 49503;
authors.forename: Patrik
authors.initials: P
authors.lastname: Brundin
authors.affiliation: Neurobiology Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, 221 84 Lund, Sweden; anders.bjorklund@med.lu.se Olle.lindvall@med.lu.se Jia-Yi.Li@med.lu.se.
authors.forename: Anders
authors.initials: A
authors.lastname: Björklund
authors.affiliation: Division of Neurology, Lund University Hospital, 221 85 Lund, Sweden; Lund Stem Cell Center, Lund University Hospital, 221 84 Lund, Sweden anders.bjorklund@med.lu.se Olle.lindvall@med.lu.se Jia-Yi.Li@med.lu.se.
authors.forename: Olle
authors.initials: O
authors.lastname: Lindvall
authors.affiliation: Neural Plasticity and Repair Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, 221 84 Lund, Sweden; anders.bjorklund@med.lu.se Olle.lindvall@med.lu.se Jia-Yi.Li@med.lu.se.
authors.forename: Jia-Yi
authors.initials: JY
authors.lastname: Li
mesh_terms: D003342:Corpus Striatum; D004298:Dopamine; D016332:Fetal Tissue Transplantation; D006801:Humans; D008636:Mesencephalon / Q000196:embryology; D009474:Neurons; D010300:Parkinson Disease; D011699:Putamen; D051844:alpha-Synuclein
chemical_list: D051844:alpha-Synuclein; D004298:Dopamine
keywords: Parkinson’s disease; autopsy; reinnervation; synucleinopathy; transplantation